Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Prostate Adenocarcinoma. Core disease mechanisms, molecular and cellular p...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 20
• Snippets retrieved: 20

Relevant Papers

[1] Inflammatory Microenvironment in Prostate Carcinogenesis

• Authors: G. Gueron, J. Cotignola, E. Vazquez
• Year: 2013
• Venue: Unknown venue
• URL: https://www.semanticscholar.org/paper/296dbc4e031505eb847327aef24cb42c32b9c3b5
• DOI: 10.5772/52636
• Citations: 1
• Summary: In this synopsis, blocking the sus‐ tained inflammatory network will offer new promising avenues to achieve significant therapeutic gains in the treatment of prostate cancer.
• Evidence snippets:
• Snippet 1 (score: 0.483) > The association between prostate cancer and inflammation was first formally addressed in the nineteen century and since then many authors have confirmed the biological and clinical evidence of this association. However, the molecular mechanism involved is yet to be deciphered. > There are two well established pathways linking inflammation and cancer: the extrinsic pathway from conditions that cause non-resolving smouldering inflammatory responses and the intrinsic pathway where the misregulation of oncogenes and tumor suppressor genes switch on the expression of inflammation-related programs. > Prostate cancer is a complex and progressive disease. Over time the cells become resistance to hormonal therapies that are designed to block the release and/or the uptake of androgens. During this stage androgen receptor (AR) mutants are able to bind promiscuous steroids, and may convert AR antagonists to agonists. Other hormones and their receptors are involved in the abnormal growth of the gland. Particularly, oestrogens and oestrogen receptors defined a subclass of prostate cancer with a very aggressive clinical phenotype (such as the TMPRSS2-ERG fusion). In addition, other signaling cascades are switched on bypassing the androgen/AR axis and favoring tumor progression. Among them, cyclooxygenase-2 (COX-2), neuroendocrine differentiation and the loss of the tumor suppressor phosphatase and tensin homolog (PTEN), with the concomitant inhibition of the PI3K/Akt, resulting in Bcl-2 overexpression and the burst of pro-inflammatory cytokines, chemokines and other growth factors production, contributing all to the progression to the hormonal-resistance disease. As in other malignancies in prostate cancer, reactive oxygen species (ROS) cause ox-idative damage to macromolecules in epithelial cells and can react with other cellular components initiating a free radical chain reaction, thus sustaining the prostate carcinogenic process and its progression. > The molecular mechanisms that prime the pathogenesis of cancer-related inflammation are complex and involve a delicate interplay between tumor and its microenvironment. In prostate tumors, the switch to an angiogenic phenotype is known to be critical for its progression.

[2] РАК ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ, СОВРЕМЕННЫЕ ТЕРАПЕВТИЧЕСКИЕ ПОДХОДЫ И ВОЗМОЖНЫЕ ПЕРСПЕКТИВЫ

• Authors: Елена Александровна Быкова, Н. А. Фалалеева, Л. Ю. Гривцова
• Year: 2020
• Venue: Unknown venue
• URL: https://www.semanticscholar.org/paper/8644d81c21f69f5c6cb3cd2e102091f425ab5eb6
• DOI: 10.17650/1726-9784-2020-19-4-18-28
• Citations: 8
• Summary: It is likely that in the future, the integration of traditional chemotherapeutic treatments and an immunological approach will be the key to effective treatment of this deadly disease.
• Evidence snippets:
• Snippet 1 (score: 0.476) > Prevalence of pancreatic cancer (PC) is not high in the population, but the aggressive nature of the disease leads to the fact that PC is one of the main causes of death in a group of patients with cancer. The prognosis for PC is significantly worse in the case of metastatic spread. It is proved that pancreatic adenocarcinoma from the very beginning is a systemic disease with early micrometastatic spread, so the question of effective drug treatment is extremely relevant. Chemotherapy is the basis for the treatment of patients with metastatic prostate cancer. However, despite numerous clinical studies using known cytostatic and targeted agents, progress in the treatment of this disease remains relatively modest compared to the progress made in the treatment of other types of tumors. The complexities of prostate cancer therapy are explained by the presence of a dense connective tissue tumor stroma, which is not just a barrier to tumor cells. It has a significant impact on various vital cellular processes, including tumor formation, invasion, metastasis, and contributes to the formation of drug resistance. Pancreatic cancer is heterogeneous in terms of molecular and biological characteristics. Many genetic changes, including germ lines and somatic mutations, contribute to the development of this disease. Recent studies have shown that each sample of prostate cancer includes an average of 63 genetic changes and 12 major signalling pathways. Further studies of tumor microenvironment markers and decoding the heterogeneity of the tumor genome in PC should become the basis for a “personalized” approach to treatment. It is likely 19 4'2020 ТОм 19 vol. 19 РОССИЙСКИЙ БИОТЕРАПЕВТИЧЕСКИЙ ЖУРНАЛ Russian journal of biotherapy Обзоры литературы that in the future, the integration of traditional chemotherapeutic treatments and an immunological approach will be the key to effective treatment of this deadly disease.

[3] PANCREATIC CANCER, CURRENT THERAPEUTIC APPROACHES AND POSSIBLE PROSPECTS

• Authors: E. A. Bykova, N. Falaleeva, L. Grivtsova
• Year: 2020
• Venue: Russian Journal of Biotherapy
• URL: https://www.semanticscholar.org/paper/3787251a542af30dfbc259e7fa2d906b1438b3f8
• DOI: 10.17650/1726-9784-2020-19-4-18-28
• Summary: It is likely that in the future, the integration of traditional chemotherapeutic treatments and an immunological approach will be the key to effective treatment of this deadly disease.
• Evidence snippets:
• Snippet 1 (score: 0.476) > Prevalence of pancreatic cancer (PC) is not high in the population, but the aggressive nature of the disease leads to the fact that PC is one of the main causes of death in a group of patients with cancer. The prognosis for PC is significantly worse in the case of metastatic spread. It is proved that pancreatic adenocarcinoma from the very beginning is a systemic disease with early micrometastatic spread, so the question of effective drug treatment is extremely relevant. Chemotherapy is the basis for the treatment of patients with metastatic prostate cancer. However, despite numerous clinical studies using known cytostatic and targeted agents, progress in the treatment of this disease remains relatively modest compared to the progress made in the treatment of other types of tumors. The complexities of prostate cancer therapy are explained by the presence of a dense connective tissue tumor stroma, which is not just a barrier to tumor cells. It has a significant impact on various vital cellular processes, including tumor formation, invasion, metastasis, and contributes to the formation of drug resistance. Pancreatic cancer is heterogeneous in terms of molecular and biological characteristics. Many genetic changes, including germ lines and somatic mutations, contribute to the development of this disease. Recent studies have shown that each sample of prostate cancer includes an average of 63 genetic changes and 12 major signalling pathways. Further studies of tumor microenvironment markers and decoding the heterogeneity of the tumor genome in PC should become the basis for a “personalized” approach to treatment. It is likely 19 4'2020 ТОм 19 vol. 19 РОССИЙСКИЙ БИОТЕРАПЕВТИЧЕСКИЙ ЖУРНАЛ Russian journal of biotherapy Обзоры литературы that in the future, the integration of traditional chemotherapeutic treatments and an immunological approach will be the key to effective treatment of this deadly disease.

[4] Immunotherapy in prostate cancer: new horizon of hurdles and hopes

• Authors: I. Tsaur, M. Brandt, E. Juengel, C. Manceau, G. Ploussard
• Year: 2020
• Venue: World Journal of Urology
• URL: https://www.semanticscholar.org/paper/8228f5608d543e0f1ae86428238acfded7d91371
• DOI: 10.1007/s00345-020-03497-1
• PMID: 33106940
• PMCID: 8514362
• Citations: 28
• Influential citations: 1
• Summary: Current evidence, based on cellular and molecular conditions, encourages further research in this field and highlights the underlying cellular mechanisms crucial for IT in PCa and gives an update of the most essential past and ongoing clinical trials in the field.
• Evidence snippets:
• Snippet 1 (score: 0.468) > Prostate cancer (PCa) is the most common malignancy in men and the cause for the second most common cancer-related death in the western world. Despite ongoing development of novel approaches such as second generation androgen receptor targeted therapies, metastatic disease is still fatal. In PCa, immunotherapy (IT) has not reached a therapeutic breakthrough as compared to several other solid tumors yet. We aimed at highlighting the underlying cellular mechanisms crucial for IT in PCa and giving an update of the most essential past and ongoing clinical trials in the field. We searched for relevant publications on molecular and cellular mechanisms involved in the PCa tumor microenvironment and response to IT as well as completed and ongoing IT studies and screened appropriate abstracts of international congresses. Tumor progression and patient outcomes depend on complex cellular and molecular interactions of the tumor with the host immune system, driven rather dormant in case of PCa. Sipuleucel-T and pembrolizumab are the only registered immune-oncology drugs to treat this malignancy. A plethora of studies assess combination of immunotherapy with other agents or treatment modalities like radiation therapy which might increase its antineoplastic activity. No robust and clinically relevant prognostic or predictive biomarkers have been established yet. Despite immunosuppressive functional status of PCa microenvironment, current evidence, based on cellular and molecular conditions, encourages further research in this field.

[5] Castration-Resistant Prostate Cancer: Targeted Therapies and Individualized Treatment

• Authors: Rahul Aggarwal, Charles J. Ryan
• Year: 2011
• Venue: The Oncologist
• URL: https://www.semanticscholar.org/paper/fab3031b6a49500f576b8f5ec721d8efb5658787
• DOI: 10.1634/theoncologist.2010-0216
• PMID: 21339259
• PMCID: 3228103
• Citations: 33
• Influential citations: 1
• Summary: Several novel therapies for castration-resistant prostate cancer targeted to androgen receptor–mediated and non–androgen receptor-mediated pathways that have recently entered clinical trials are highlighted.
• Evidence snippets:
• Snippet 1 (score: 0.462) > Although most men who develop prostate cancer do not die from their disease, those who develop castration-resistant prostate cancer (CRPC) have a poor prognosis and are more likely to die from complications of metastatic disease than from comorbid illness. Approved systemic chemotherapies for CRPC provide limited benefits. Docetaxel, a taxane inhibitor of microtubule function, remains the standard firstline treatment based on two phase III trials that showed a median survival time of 18 -19 months [1,2]. Efforts are ongoing to develop various therapies targeting mechanisms behind tumor progression. Several molecular pathways have been implicated in prostate cancer progression from localized disease that remains sensitive to androgen deprivation to CRPC, the lethal tumor phenotype. Pathways can be divided into those mediated by the androgen receptor (AR) and those without direct agonism of the AR [3]. Novel therapies have been rationally designed to target molecular pathways involved in oncogenesis and disease progression although results from trials have been mixed. The biologic heterogeneity of CRPC, including potential involvement of AR-mediated or AR-independent pathways, is a probable cause of the variable responses seen with targeted therapies. Arguably, a more rational approach could involve determining the biologic status of an individual tumor before therapy by assessing gene expression, hormone metabolism, or signaling activity, and directing treatment accordingly. This more individualized approach is being tested in early-phase clinical trials. > Here, we highlight several novel therapies for CRPC targeted to AR-mediated or non-AR-mediated pathways that have recently entered clinical trials, including the molecular rationale and available clinical data. We also summarize emerging evidence on the potential of individualized therapy for CRPC.

[6] Fatty Acid Synthesis in Prostate Cancer: Vulnerability or Epiphenomenon?

• Authors: Laura A. Sena, S. Denmeade
• Year: 2021
• Venue: Cancer Research
• URL: https://www.semanticscholar.org/paper/6cccb007906263932d78cf7ce1d86fa90a9e8a0a
• DOI: 10.1158/0008-5472.CAN-21-1392
• PMID: 34145040
• PMCID: 8416800
• Citations: 50
• Influential citations: 2
• Summary: Evidence indicating that fatty acid synthesis drives progression of prostate cancer is summarized and explanations for this phenomenon are explored and future directions for targeting this pathway for patient benefit are discussed.
• Evidence snippets:
• Snippet 1 (score: 0.457) > 20:1n9 or 11) are higher in primary prostate cancer compared with benign prostate, and may be higher still in metastatic prostate cancer (34)(35)(36). Although linoleate is considered an essential polyunsaturated fatty acid (PUFA) that must be taken up by the cell, the remainder of these fatty acids can be synthesized de novo. Conversely, quantity of the fatty acid precursor citrate is reduced in high versus low Gleason score primary prostate cancer, which may indicate high utilization (37,38). Finally, noninvasive molecular imaging techniques using positron emission tomography (PET) also support the concept that prostate cancer engages in de novo fatty acid synthesis. While glucose uptake is generally low in prostate cancer (as assessed by 18 F-fluorodeoxyglucose PET), acetate uptake is higher (as assessed by 11 C-acetate PET) and is predictive of biochemical relapse after prostatectomy (39,40). Acetate uptake seems to be used for de novo fatty acid synthesis because it is diminished by inhibitors of FASN (41,42). > While these data suggest that de novo fatty acid synthesis occurs in human prostate cancer, and with increasing rate with disease progression (Fig. 2D), this could be assessed more definitively using isotope tracing followed by assessment of labeling patterns by mass spectrometry in biopsy samples of patients, as has been performed in patients with renal cell carcinoma (43). Moreover, given that cellular metabolic flux is shaped by both cell-intrinsic factors and the microenvironment (44), future studies should consider how prostate cancer cell rates of fatty acid synthesis are altered depending on composition of surrounding cell types (i.e., anatomic location of the metastasis) and metabolite and oxygen availability. These studies are critically important not only to better define the pathophysiology of prostate cancer, but also to identify biomarkers of high rates of fatty acid synthesis that may predict clinical response to inhibitors of this pathway.

[7] Signalling pathways in a nutshell: from pathogenesis to therapeutical implications in prostate cancer

• Authors: A. P. Goncharov, C. Dicusari Elissaiou, E. Ben Aharon Farzalla, Giorgi Akhvlediani, Nino Vashakidze et al.
• Year: 2025
• Venue: Annals of Medicine
• URL: https://www.semanticscholar.org/paper/dc4711ef4df5ade8cec4dffd04d8e085044e0a32
• DOI: 10.1080/07853890.2025.2474175
• PMID: 40372974
• PMCID: 12082737
• Citations: 3
• Summary: This review will discuss the different signalling pathways, such as TGF-β, Cripto-1, Wnt pathways, Hedgehog, Notch and NF-κB pathways, and how they promote tumour initiation and progression by influencing diverse cellular processes and EMT in general and in benign and malignant prostate tumours.
• Evidence snippets:
• Snippet 1 (score: 0.448) > Prostate cancer is the second most common tumour in men after skin cancer. It is considered the second most common cause of cancer-related deaths amongst men in the United States and fifth globally [1,2]. Prostate cancer classification and staging systems are based on clinical and laboratory evaluation, as well as imaging and histological classification [3]. > According to treatment response and clinical and histopathological features, tumours may be classified as organ-confined, locally advanced, metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), or as a lethal disease [3][4][5]. > mCRPC is further divided into five subgroups according to the histologic characteristics and the expression of androgen receptor (AR) and neuroendocrine (NE) markers: adenocarcinoma (AR + /NE − ), double-positive (AR + /NE + ), low AR (ARL/NE − ), neuroendocrine (AR − /NE + ), and double-negative (AR − /NE − ) [6]. > The treatment lines vary between the types and are directly related to the extent of tumour progression. The epithelial-mesenchymal transition (EMT) is an integral stage in determining the invasive potential, progression, and aggressiveness of the tumour [7]. Our group has previously described the importance of the EMT process and its mechanism of action in benign and malignant prostate tumours. Initiation of the EMT process requires the activation of various signalling pathways within the cell. Later, cells reduce the expression of proteins such as E-cadherin, β-catenin, Desmoplakin, Syndecan, and several others. At the same time, proteins that are related to mesenchymal phenotypes, such as Vimentin, Fibronectin, Snail, and Slug, are upregulated [8]. A harsh tumour environment encourages the utilisation of different mechanisms to promote tumour survival and proliferation. Changes in the tumour microenvironment are essential; therefore, it is important to point out the different mechanisms leading to EMT [9].

[8] Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies

• Authors: Aasems Jacob, Rishi Raj, Derek B. Allison, Zin W. Myint
• Year: 2021
• Venue: Cancers
• URL: https://www.semanticscholar.org/paper/93d425f8fbbccd8b90f442fbef73e8e7508c3ee3
• DOI: 10.3390/cancers13215417
• PMID: 34771580
• PMCID: 8582395
• Citations: 104
• Influential citations: 3
• Summary: This review article details the current evidence on clinically relevant driver mechanisms, relevant biomarkers, and treatment modalities to overcome resistance of androgen receptor (AR) in prostate cancer.
• Evidence snippets:
• Snippet 1 (score: 0.439) > Simple Summary Early-stage and castration-sensitive prostate cancer (PCa) growth is solely mediated by androgen signaling pathways. AR signaling inhibitors (ARSIs) have significantly improved clinical outcomes among men with PCa. In the metastatic castration-resistant PCa, there is presence of both androgen-dependent and androgen-independent cells driving the tumor growth. Despite the use of ARSIs, disease progression ultimately occurs in all patients with PCa and is due to genetic alterations in ARs, resulting in the outgrowth of androgen-independent cells. The possible mechanisms include development of AR splice variants of which AR-V7 is more common, AR point mutations, and AR overexpression. In addition, restoration of downstream signaling through alternate pathways can also lead to androgen-independent growth of PCa. Therapeutic strategies to overcome these resistance mechanisms and establish predictive biomarkers are still in clinical trials. This review article details the current evidence on clinically relevant driver mechanisms, relevant biomarkers, and treatment modalities to overcome resistance. Abstract Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor-abiraterone and androgen receptor antagonists-enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and is not targeted by available ARSIs. Non-androgen receptor dependent resistance mechanisms are mediated by activation of an alternative signaling pathway when AR is inhibited. DNA repair pathway, PI3K/AKT/mTOR pathway, BRAF-MAPK and Wnt signaling pathway and activation by glucocorticoid receptors can restore downstream signaling in prostate cancer by alternative proteins. Multiple clinical trials are underway exploring therapeutic strategies to overcome these resistance mechanisms.

[9] Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

• Authors: W. Tulalamba, T. Janvilisri
• Year: 2012
• Venue: International Journal of Cell Biology
• URL: https://www.semanticscholar.org/paper/307cb9186444d9dad6e2e3b53763be0de76de186
• DOI: 10.1155/2012/594681
• PMID: 22500174
• PMCID: 3303613
• Citations: 93
• Influential citations: 5
• Summary: The molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression and the important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.
• Evidence snippets:
• Snippet 1 (score: 0.436) > In the pregenomic eras, highly integrated and complex circuitry of molecular signaling in NPC pathogenesis was only partially understood. Over the past decade, the knowledge of the molecular mechanisms in NPC carcinogenesis has been rapidly accumulated. Dysregulation and abnormal protein expression of molecules in certain signaling pathways involved in cellular functions including proliferation, adhesion, survival, and apoptosis has been demonstrated in the NPC cells. Detailed information on the complex network in signaling pathway leading to a coordinated pattern of gene expression and regulation in NPC will undoubtedly provide important clues to develop novel prognostic and therapeutic strategies for this cancer. Refining molecular markers into clinically relevant assays may assist in the detection of NPC in asymptomatic patients, as well as stage classification and monitoring disease progression and treatments. Furthermore, selective regulation of particular proteins targeting cancer cell proliferation, invasion, and apoptosis is a hopeful prospect for future anticancer therapy that slow disease progression and improve survival.

[10] Anti-Proliferative Effect and Induction of Apoptosis in Androgen-Independent Human Prostate Cancer Cells by 1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one

• Authors: Kamini Citalingam, F. Abas, N. Lajis, Iekhsan Othman, R. Naidu
• Year: 2015
• Venue: Molecules
• URL: https://www.semanticscholar.org/paper/1b9c5630e11eb31d7ddfa705fae8ceaa19d66408
• DOI: 10.3390/molecules20023406
• PMID: 25690296
• PMCID: 6272399
• Citations: 27
• Influential citations: 1
• Summary: In conclusion, MS17 demonstrated anti-proliferative effect and induces apoptosis in a time and dose-dependent manner suggesting its potential for development as an anti-cancer agent for androgen-independent prostate cancer.
• Evidence snippets:
• Snippet 1 (score: 0.430) > Prostate cancer is one of the most commonly diagnosed cancers and a leading cause of cancer death in men. Prostate cancer is a clinically heterogeneous disease which harbors multiple genetic abnormalities accumulated during the progression of the disease. The cellular mechanisms contributing to prostate cancer involve a multistep process that includes the inactivation of tumor suppressor genes and the dysregulation of several oncogenic pathways. Although the exact causes of prostate cancer remain unclear, it has been well documented that androgens (testosterone and 5α-dihydrotestosterone, DHT) play an important role in the physiological development of the normal prostate and prostate cancer [1]. Exposure to higher levels of androgens or overexpression/mutation of androgen receptor often leads to rapid proliferation of prostate cancer cells and, almost all the patients eventually relapse with tumors that become androgen-independent [2,3]. At this stage, the cancer cells begin to metastasize to various organs, ultimately causing the death of the patient. > At the initial stage prostate tumors respond to hormonal therapies, and currently available chemotherapeutic drugs are successful in treating these localized, androgen-dependent cancer. These tumors eventually progress to androgen-independent forms that are refractory to these therapies and treatment thus remains hindered and represents a challenge for the clinical oncologist [4]. This has led to little overall improvement of morbidity and mortality, and therefore novel drugs are required to treat hormone-resistant prostate cancer. Alterations of several molecular pathways are required for the development of androgen independence and the dilemma is how to develop the most effective therapeutic drugs that are required to treat hormone-resistant prostate cancer. Tumor cells activate multiple pathways to survive under castration levels of androgens [5][6][7]. > Curcumin (diferuloylmethane), an active yellow pigment, is a major active component of turmeric. It is isolated from the rhizomes of Curcuma longa and has been widely used for decades in the Asian countries, particularly in South Asia.

[11] The Potential of Metabolomics in Biomedical Applications

• Authors: V. González-Covarrubias, E. Martínez-Martínez, L. del Bosque-Plata
• Year: 2022
• Venue: Metabolites
• URL: https://www.semanticscholar.org/paper/abed08d7a691cf6b996b465706dc62a5591731ec
• DOI: 10.3390/metabo12020194
• PMID: 35208267
• PMCID: 8880031
• Citations: 163
• Influential citations: 5
• Summary: This review focuses on the metabolomics that can be applied to improve human health, as well as its trends and impacts in metabolic and neurodegenerative diseases, cancer, longevity, the exposome, liquid biopsy development, and pharmacometabolomics.
• Evidence snippets:
• Snippet 1 (score: 0.428) > The detected metabolic differences between ERG-positive and ERG-negative prostate cancer demonstrate that the increment in β-oxidation and purine metabolism regularly described for prostate cancer could be principally attributed to TMPRSS2-ERG-negative (transmembrane serine protease 2 (TMPRSS2)) tumors. These results agree with the view that ERG-positive (ETS-Related Gene (ERG)) and ERG-negative prostate tumors should be considered partly different diseases, which may require different treatment strategies. > MacKinnon et al. described the metabolites involved in an androgen-dependent prostate cancer cell line [125]. Methyltrienolone (an androgen receptor agonist) treatment resulted in a metabolic signature characteristic of aggressive prostate cancer. Specifically, researchers observed a decrease in myoinositol, altered glutathione levels, a perturbation of amino-acid levels, a decreased level of methionine, a high level of phosphocholine (PC), and an increase in the phosphocholine/glycerophosphocholine ratio. These metabolites may be useful for monitoring cancer development and aggressiveness [125]. > The in vivo detection of clinically relevant prostate cancer can be improved using metabolomics-derived markers related to Gleason score with non-invasive methods, as is the case for magnetic resonance imaging or positron emission tomography imaging. Analogues of PC, glutamate, and glucose, as identified here, are already applied in prostate cancer studies and have been approved by the U.S. Food and Drug Administration (FDA) for the positron emission tomography imaging of recurrent prostate cancer. The researchers discovered two additional metabolites associated with prostate cancer: hypoxanthine and arginine. Both are associated with prostate cancer recurrence and progression [57]. (see Table 1). > Although it is used less frequently than the other omics approaches, metabolomics has the potential to significantly affect core areas of oncology, including screening, diagnosis, and therapy. However, such applications require a better understanding of how these measurements are connected to human physiology and cancer biology.

[12] Genome-wide differential gene network analysis R software and its application In LnCap prostate cancer

• Authors: Gökmen Altay, D. Neal
• Year: 2017
• Venue: bioRxiv
• URL: https://www.semanticscholar.org/paper/8ceb36aeccf2c5e6835634e22aa7391bd1e4c4d5
• DOI: 10.1101/129742
• Summary: An R software package for condition-specific gene regulatory network analysis based on DC3NET algorithm is introduced and how to derive condition-specific gene targets from expression datasets on genome-wide level using differential gene network analysis is demonstrated.
• Evidence snippets:
• Snippet 1 (score: 0.426) > Prostate cancer is the second most common cancer in the male population, with an estimated 417,000 new cases diagnosed each year in Europe (Ferlay, 2013).The activation of androgen receptor (AR) through androgens plays a crucial role in the development and progression of prostate cancer (Kaur, 2016;Anantharaman, 2015;Choudhary, 2011;Massie, 2011).For early detection of prostate cancer, prostate specific antigen (PSA) screening method has been used widely as a diagnostic tool (Karatas, 2015).However, PSA fails to discriminate indolent disease which results in over-diagnosis and this may lead to poor prognosis (Abou-Ouf, 2015;Ma, 2015;Myers, 2015).Furthermore, there is no evidence showing that the PSA screening reduces the incidence of death and the underlying mechanism of prostate cancer progression remains largely unknown (Cannistraci, 2014 ;Ren, 2015). > Nowadays, the identification of novel oncogenes or tumor suppressor genes has become popular in tumorigenesis studies in understanding molecular mechanisms that drive disease progression (Ren, 2015).Understanding the working mechanism of molecules in normal cell physiology and pathogenesis allows subtle drug development and helps treatment of a disease, such as cancer (Altay, 2010;Rual, 2005;Schadt, 2009).The advent of systems and network biology enable us to capture interactions occurring within a cell, which can be represented as gene networks.Computational analysis of the networks provides key insights into biological pathways and cellular organization (Altay, 2011). > The biological processes at the gene level are very complex structures as genes dynamically interact with each other.The interactions of these molecules have been changing significantly over time and in different cell conditions such as from normal to cancer (Emmert-Streib, 2012;Califano, 2011).A single gene can participate in different biological processes and regulate different genes at different times.However, diseases are usually consequences of interactions between multiple molecular processes, rather than an abnormality in a single gene (Menche, 2015). > Gene regulatory networks hold the potential to identify specific subnetworks that are dysfunctional in the disease state of a cell.

[13] Altered amino and fatty acids metabolism in Sudanese prostate cancer patients: insights from metabolic analysis

• Authors: Dalia Ahmed, E. Abdel-Shafy, Elsadig Ahmed Adam Mohammed, Husam Elden Alnour Bakhet Alnour, Amar Mohamed Ismail et al.
• Year: 2024
• Venue: Journal of Circulating Biomarkers
• URL: https://www.semanticscholar.org/paper/9078ef15ce82d6a27fa0fdeca6e6744d0364336f
• DOI: 10.33393/jcb.2024.3146
• PMID: 39697480
• PMCID: 11653783
• Citations: 2
• Summary: High levels of fatty acids, phospholipids, cholesterol, valine, leucine, and isoleucine associated with non-hypertensive patients were revealed, and hypertensive patients were associated with high GlycA and GlycB levels and altered amino acid metabolism.
• Evidence snippets:
• Snippet 1 (score: 0.423) > Prostate cancer (PCa) poses a significant global health challenge, characterized by its increasing incidence and investigation of altered metabolic pathways involving lipids, fatty acids, and free amino acids holds immense importance in understanding the molecular mechanisms driving PCa pathogenesis (10,11). > Among the plethora of molecular factors implicated in PCa pathogenesis, lipids have emerged as pivotal players, governing diverse cellular processes crucial for tumor progression (12). Emerging evidence suggests a complex interplay between lipid metabolism, HTN, and androgen deprivation therapies (ADTs) in PCa patients, adding further layers of complexity to patient care (13,14). Dysregulated lipid metabolism not only fuels the energy demands of proliferating cancer cells but also contributes to the structural integrity of cellular membranes and facilitates signaling pathways crucial for PCa progression (15). Fatty acids, the building blocks of complex lipids, are intricately involved in various cellular processes, including energy production, membrane synthesis, and signaling modulation (16). Perturbations in fatty acid metabolism have been implicated in PCa pathophysiology, influencing tumor aggressiveness, therapeutic resistance, and disease prognosis (17). Metabolomic studies have unveiled alterations in fatty acid composition and metabolism associated with PCa, highlighting their potential as biomarkers for disease diagnosis and therapeutic targets for intervention (10,18). Moreover, free amino acids play pivotal roles in cellular metabolism, serving as precursors for protein synthesis, energy production, and signaling molecules (19). Alteration in amino acid metabolism has been implicated in PCa progression, influencing cell proliferation, invasion, and metastasis (20,21). Metabolomic profiling has uncovered variations in amino acid levels and metabolism in PCa, offering insights into the relation between metabolic rewiring and oncogenic signaling pathways (8,11). > Most metabolomic PCa studies are conducted predominantly in European and Asian populations. The generalization of findings to other ethnic groups may be limited due to inherent genetic, environmental, and lifestyle differences (22). Therefore, investigating altered metabolic pathways in diverse populations, including those from African regions like Sudan, is crucial for elucidating population-specific variations in PCa biology.

[14] Mitochondrial oncobioenergetics of prostate tumorigenesis

• Authors: P. Vayalil
• Year: 2019
• Venue: Oncology Letters
• URL: https://www.semanticscholar.org/paper/adecfdca7304673545f754879e9b84e22e0d076a
• DOI: 10.3892/ol.2019.10785
• PMID: 31611945
• PMCID: 6781517
• Citations: 12
• Influential citations: 1
• Summary: Since PC is a slow growing tumor, modulating the MOB profile at specific stages of tumor development may be a novel approach to treat or prevent PC.
• Evidence snippets:
• Snippet 1 (score: 0.422) > Prostate cancer (PC) is a disease of the old age (1). The specific underlying mechanisms of prostate carcinogenesis have not been unraveled yet. The only well-established risk factors for PC are older age, black race/ethnicity, and a family history of the disease (2,3). Therefore, future progress in combating PC will be highly dependent upon an understanding of the mechanisms involved in the development and steady progression into prostate malignancy. > Mitochondria are emerging as key players in the tumorigenic process of cells by maintaining the biosynthetic and energetic capabilities of cancer cells. Besides compartmentalizing different metabolic pathways, the mitochondria is engaged in the generation of much of the cellular energy, regulation of the redox state of the cell, generation of reactive oxygen species (ROS), buffering Ca 2+ and initiating apoptosis (4). Mitochondria are involved in the final stage of the cellular catabolism and maintain the redox homeostasis at different levels. Through several enzymatic reactions, carbohydrates, fats and proteins are degraded into smaller molecules, which is further converted to pyruvate by glycolysis, fatty acids and amino acids (Fig. 1). Mitochondria further transform these small molecules into NADH and FADH 2 (reduced energy equivalents), through β-oxidation and TCA cycle or rerouted to biosynthetic pathways. The reduced energy equivalents are then utilized by the mitochondrial electron transport chain (ETC) through oxidative phosphorylation (OXPHOS). The electrons liberated by the oxidation of NADH and FADH 2 are passed along a series of carriers of ETC located in mitochondrial inner membrane. The electrons are ultimately transferred to molecular oxygen to form water (Fig. 2). ETC consists of four enzyme complexes (complexes I-IV), and two electron carriers (coenzyme Q and cytochrome c). These complexes are composed of numerous protein subunits encoded by nuclear and mitochondrial genes, except complex II, which are encoded by nuclear genes only.

[15] Identification of key pathways and genes in PTEN mutation prostate cancer by bioinformatics analysis

• Authors: Jian Sun, Shugen Li, Fei Wang, Caibin Fan, Jianqing Wang
• Year: 2019
• Venue: BMC Medical Genetics
• URL: https://www.semanticscholar.org/paper/a23ddabb812d435439d6a7a35b3d777e8f445d1f
• DOI: 10.1186/s12881-019-0923-7
• PMID: 31791268
• PMCID: 6889628
• Citations: 55
• Influential citations: 1
• Summary: It is suggested that PTEN mutation in prostate cancer may induce changes in a variety of genes and pathways and affect disease progression, suggesting the significance of PTen mutation in individualized treatment of prostate cancer.
• Evidence snippets:
• Snippet 1 (score: 0.421) > PTEN, which is a tumor suppressor protein and is very commonly lost across cancer types [19]. The major function of PTEN depends on its phosphatase activity. PTEN mainly inhibits PI3K/AKT pathway activity, while other studies also suggest that PTEN may function through AKT-independent [8]. Mutations in PTEN result in losing its phosphatase activity, which contribute to the Here in our study, we analyzed the gene expression data of prostate cancer obtained from TCGA to uncover the critical pathways and top hub genes associated with PTEN mutation. We found 22% patients with PTEN mutation among all cases. The mRNA expression and clinical affair analyses showed lower expression level of PTEN, higher Gleason score and poorer prognosis in patients with PTEN mutation, which indicated the significance of PTEN mutation in prostate cancer: PTEN mutation correlated with advanced disease and worse outcome. PTEN deletion, transcriptional and epigenetic modifications of PTEN are known mechanisms that could cause deregulation of PTEN [20,21]. Lower PTEN expression level often correlates to disease progression in various cancer types [22][23][24], which makes it one of the important potential mechanisms how PTEN mutation exert the role in disease progression. In the following research, the relationship between PTEN mutation and more details of clinical affairs of prostate cancer requires larger sample data for more accurate results. Now that PTEN mutation contributes to prostate cancer progression, the mechanisms underlying other than PTEN downregulation are critical. GSEA analysis suggests that PTEN mutation were mainly associated with the cell metabolism, proliferation and cancer related pathways. In the cellular processes above, metabolic processes, including glycolysis and lipid metabolism, always play critical roles in cancer progression. Previous studies have shown that the formation of cancer cells requires adaptations across various metabolic processes to satisfy the energy required for their increased rate of proliferation. Dysregulation of lipid metabolism, including upregulation of several lipogenic enzymes, has been a hallmark of prostate cancer, and metabolic target has been shown to be a potential treatment target in prostate cancer [25,26]. Our results indicated that drugs targeting lipid metabolic pathways could contribute to the development of new therapeutic modalities in PTEN mutation prostate cancer

[16] Melatonin and Prostate Cancer: Anti-tumor Roles and Therapeutic Application

• Authors: Mark F. Megerian, Jae Seok Kim, Jad Badreddine, Sung Hwi Hong, L. Ponsky et al.
• Year: 2023
• Venue: Aging and Disease
• URL: https://www.semanticscholar.org/paper/15af79038c0432b8f59fa955221bcbb8dc202331
• DOI: 10.14336/AD.2022.1010
• PMID: 37191417
• PMCID: 10187692
• Citations: 15
• Summary: The currently known mechanisms of melatonin-mediated oncostasis in prostate cancer are described, including those that relate to the indolamine’s ability to modulate metabolic activity, cell cycle progression and proliferation, androgen signaling, angiogenesis, metastasis, immunity and oxidative cell status, apoptosis, genomic stability, neuroendocrine differentiation, and the circadian rhythm.
• Evidence snippets:
• Snippet 1 (score: 0.419) > One of the many ways by which tumor cells alter their metabolic activity to sustain survival is to increase the uptake and utilization of glucose. The Warburg Effect describes the reliance of tumor cells on anaerobic respiration through the glycolytic pathway rather than mitochondrial aerobic respiration, even in the presence of oxygen [33]. For this reason, Otto Warburg dubbed this seemingly paradoxical phenomenon aerobic glycolysis in the 1920s [34], and since then, extensive research has elucidated numerous mechanisms of increased glucose uptake and utilization that support this unique metabolic phenotype in tumor cells [35]. In prostate cancer, glucose metabolism is involved in the progression of carcinogenesis [36], where oxidative phosphorylation is active early in disease progression [37], and the Warburg effect takes over in later stages of the disease [38]. The role of melatonin in glucose bioenergetics of prostate cancer has been studied. After previously demonstrating that the major mechanism of melatonin uptake in LNCaP and PC-3 prostate cancer cells were mediated via an active process rather than passive diffusion [39], Hevia et al. later demonstrated a melatonin receptor-independent mechanism of melatonin uptake through members of the glucose transporter (GLUT) family transporters. Specifically, indolamine was found to interact at the same location as GLUT1 and prevented glucose uptake after 30 min, 1, 3, and 6 hours. Intracellular melatonin concentration was diminished as well with the administration of glucose and other known GLUT1 competitive ligands, suggesting competition between melatonin and glucose by the glucose transporter. This competition was then demonstrated in vivo where pharmacological doses of melatonin attenuated the glucose-induced tumor progression and prolonged transgenic adenocarcinoma of the mouse prostate (TRAMP) mice survival [40]. > The same research team further examined the specific roles of melatonin in prostate cancer metabolism. Utilizing 13C-labeled metabolites and measuring adenosine triphosphate (ATP)/adenosine monophosphate (AMP) levels and lactate dehydrogenase and pentose phosphate pathway activity, Hevia et al. discovered numerous melatonin-induced metabolic

[17] Differential but Concerted Expression of HSD17B2, HSD17B3, SHBG and SRD5A1 Testosterone Tetrad Modulate Therapy Response and Susceptibility to Disease Relapse in Patients with Prostate Cancer

• Authors: O. Bamodu, Kai-Yi Tzou, Chia-Da Lin, Su-Wei Hu, Yuan-Hung Wang et al.
• Year: 2021
• Venue: Cancers
• URL: https://www.semanticscholar.org/paper/e0c4d3081fa727779e464de749f88d0b405d1fd5
• DOI: 10.3390/cancers13143478
• PMID: 34298692
• PMCID: 8303483
• Citations: 8
• Summary: The findings highlight the role and exploitability of testosterone metabolic reprogramming in prostate TME for patient stratification and personalized/precision medicine based on the differential but concerted expression of molecular components of the proposed testosterone tetrad in patients with therapy-refractory, locally advanced, or recurrent PCa.
• Evidence snippets:
• Snippet 1 (score: 0.417) > Predicting therapy response and/or clinical outcome in patients with newly diagnosed PCa is challenging. This is in part because of the current non-standardized imaging methods for assessing disease dissemination and the confounding dynamism of the most frequently altered PCa-associated biomarker, prostate-specific antigen (PSA), which makes the latter a less reliable or accurate surrogate biomarker of disease course or treatment response. For instance, about 20% of patients with CRPC who later respond to chemotherapy would have been tagged "non-responders" because of an initial persistent rise in PSA level, which did not decline until after week 12 of chemotherapy or did not decline at all when on immune checkpoint blockade therapy [10]. This modest or non-association between changes in post-treatment PSA level and therapy response or disease recurrence highlights a critical unmet need in PCa management-the need for more reliable and accurate indicators of patient status, namely therapy response or disease recurrence. > Advances in tumor biology increasingly highlight the genomic complexity of cancerous cells, irrespective of tissue origin or histological sub-type [11]. However, within this broad genomic/genetic landscape, some cancer types are more dependent on certain oncogenic pathways for survival than others. This state of preferential "oncogene addiction" is common with aberrant oncometabolic activity, and provides therapeutic basis for molecular targeting of dysregulated oncogenic metabolites [11]. The apparent dependence of cancerous prostate cells on androgen/testosterone metabolic signaling for their survival and the maintenance of their malignant therapy-resistant and recurrent phenotypes makes molecular components of testosterone metabolic reprogramming exploitable for reliably accurate prediction of disease course, therapy response, and clinical outcome, thus, aiding patient stratification and informing therapeutic decision-making when managing patients just diagnosed with PCa. > The present study harnesses the profiling of disease-relevant molecular players, namely testosterone metabolites, HSD17B2, HSD17B3, SHBG, and SRD5A1 to provide an evidence-based platform for exploring and identifying biomarkers that may inform patient stratification, allow prediction of treatment efficacy, and determine mechanism(s) of drug resistance

[18] AMPed up to treat prostate cancer: novel AMPK activators emerge for cancer therapy

• Authors: M. Schiewer, K. Knudsen
• Year: 2014
• Venue: EMBO Molecular Medicine
• URL: https://www.semanticscholar.org/paper/92b6a0d8b95812d9b2d4f54129102bc67937fc14
• DOI: 10.1002/emmm.201303737
• PMID: 24562461
• PMCID: 3992071
• Citations: 5
• Summary: A new study by Zadra et al identifies the energy sensor AMPK (5′ AMP‐activated kinase) as a viable therapeutic target in prostate cancer.
• Evidence snippets:
• Snippet 1 (score: 0.417) > D espite recent advances in the treatment for metastatic prostatic adenocarcinoma (MacVicar & Hussain, 2013), clinical management of this tumor type remains a major challenge, and there is as of yet no durable cure for advanced disease. Prostate cancer generally responds poorly to standard chemotherapy, but is heavily dependent on signaling of the androgen receptor (AR) for growth and survival (Knudsen & Penning, 2010). Thus, the mainstay of treatment targets this dependence, combining mechanisms to either deplete the AR of ligand or through the use of direct AR antagonists. Although these strategies are initially effective, recurrent tumors deemed "castrate-resistant prostate cancer" (CRPC) ultimately arise. Developing pathways that could be co-targeted alongside AR or that would otherwise thwart the development of the CRPC is a current translational and clinical priority. > In this issue, a new study by Zadra et al (2014) identifies the energy sensor AMPK (5′AMP-activated kinase) as a viable therapeutic target in prostate cancer. AMPK is a serine/threonine kinase that functions as a metabolic sensor that is sensitive to AMP/ ATP levels and serves to enhance ATP generation (Hardie, 2011). In mammalian cells, the kinase exists as a heterotrimer comprised of a single a (catalytic) subunit in addition to two ß and c regulatory subunits as such, variant AMPK complexes exist and may be divergent dependent on cellular context. In spite of this complexity, common activation events occur when the  subunit is phosphorylated on threonine 172, which occurs in the T-loop (Carling et al, 2012 The cellular function of AMPK is to respond to metabolic state and oncogenic stress. Activated AMPK induces catabolic metabolism and suppresses the anabolic state, thereby inhibiting cellular proliferation and potentially serving a tumor suppressive role (Liang & Mills, 2013). Consistent with this idea, AMPK loss can promote tumor progression, as genetic deletion of the AMPK a1 subunit potentiated Myc-induced lymphomagenesis (Faubert et al, 2013). At the molecular level, the tumor suppressive role of activated AMPK is associated with inhibition of cell cycle progression, cholesterol and fatty acid

[19] Characterization of the Biochemical Recurrence Prediction Ability and Progression Correlation of Peroxiredoxins Family in Prostate Cancer Based on Integrating Single‐Cell RNA‐Seq and Bulk RNA‐Seq Cohorts

• Authors: Shan Tang, Jinchuang Li, W. Tian, Yuanfa Feng, Yu-Chiao Deng et al.
• Year: 2025
• Venue: Cancer Medicine
• URL: https://www.semanticscholar.org/paper/4ce2d7c8df3aa94185cbd786253fec27032e2998
• DOI: 10.1002/cam4.70855
• PMID: 40281661
• PMCID: 12031674
• Citations: 1
• Influential citations: 1
• Summary: The peroxiredoxins (PRDXs) family plays a crucial role in balancing reactive oxygen species (ROS) levels in tumor cells. However, its potential role in prognosis and therapy response of prostate cancer (PCa) remains unknown.
• Evidence snippets:
• Snippet 1 (score: 0.416) > Prostate cancer (PCa) is one of the most prevalent cancers in the world, with 299,010 new cases in the United States in 2024 and 1,466,680 new cases globally in 2022 [1,2]. Most PCa is indolent at the time of diagnosis. Biochemical recurrence (BCR) is a critical stage in the progression of PCa [3]. Approximately 35% of patients experience BCR after receiving radical prostatectomy (RP) or radiation therapy (RT), with elevated prostate-specific antigen (PSA) levels commonly used as a reference in clinical practice [4]. Once PCa progresses to a more advanced stage, it advances rapidly and significantly increases the mortality rate of patients [5]. Without proper treatment, about 40% of patients will experience prostate cancer-specific death within 15 years [6]. Drug resistance is a major cause of treatment failure in PCa. Thus, clinicians must assess whether patients require personalized therapy. Exploring a reliable criteria to identify high-risk patients and the underlying mechanisms of BCR are urgently needed. > Reactive oxygen species (ROS), a wide set of unstable oxygencontaining molecules, are typical by-products of cellular metabolism and serve as signaling agents, impacting a range of cellular processes [7]. An alteration in the equilibrium of redox homeostasis, whether due to excessive or inadequate generation of ROS, can have detrimental effects and is associated with several clinical diseases [8,9]. Elevated ROS levels can inhibit tumor cell growth by inducing oxidative DNA damage, enhancing cell cycle arrest, and promoting apoptosis [10][11][12]. The capacity to manage ROS from mitochondrial oxidative metabolism determines the proliferative outcome of cancer cells [13]. In addition, commonly used chemotherapeutic medications exhibit anti-tumor actions, partially by inducing high levels of ROS [14]. The capacity of cancer cells to adapt to inherent or drug-induced oxidative stress plays a role in their resistance to chemotherapy and ultimately contributes to the progression of the disease [15,16].

[20] Hormonal therapy and chemotherapy in hormone-naive and castration resistant prostate cancer

• Authors: F. Recine, C. Sternberg
• Year: 2015
• Venue: Translational Andrology and Urology
• URL: https://www.semanticscholar.org/paper/414cf853b7e613b33701d3034cf69d3e53929cad
• DOI: 10.3978/j.issn.2223-4683.2015.04.11
• PMID: 26816835
• PMCID: 4708230
• Citations: 24
• Influential citations: 2
• Summary: The management of advanced castration resistant prostate cancer (CRPC) has been rapidly changing and is still evolving.
• Evidence snippets:
• Snippet 1 (score: 0.415) > Even though the AR plays a major role in the progression to CRPC, alternative pathways can have a role in stimulating prostate cancer cells, confirming the cellular heterogeneity in prostate cancer (39,40). > Prostate cancer cells can develop alternative AR independent molecular pathways for survival that bypass AR activation, including cancer stem cells, receptor tyrosine kinases and neuroendocrine differentiation (NE) (41). A potential mechanism for survival in the castrate environment is the presence of prostate cancer stem cells that continually supply the cancer cell population, despite therapy. These cells are not affected by ADT and can differentiate into androgen dependent and independent cells, leading to a heterogeneous phenotype of AR (42,43). > Activation of the PI3 kinase signaling pathway is critical for the survival of prostate cancer cells. PTEN is a tumor suppressor and has lipid phosphatase activity that metabolizes PIP3 (phosphatidylinositol triphosphate). The PTEN function is expressed primarily through negative regulation of the PI3K/Akt pathway. PTEN is inactivated in several types of cancers, including prostate cancer. Loss of PTEN function in prostate cancer can occur through several mechanisms, including deletion, mutation and methylation. These events can cause tumor cell survival through selective pressure caused by ADT (44)(45)(46). > Another potentially relevant pathway is NE of tumor cells in prostate cancer. The prevalence of NE cells in prostate adenocarcinoma varies from 30% to 100% and they do not express the AR. These cells may develop from a predominantly adenocarcinoma PSA secreting environment under the pressure of ADT. NE cells may contribute to the progression to CRPC through the production of neurosecretory products, such as parathyroid hormone-related protein, the neurotransmitter serotonin, the neuropeptide hormone bombesin, calcitonin, chromagranin A, neurotensin, and thyroid-stimulatory hormone (6,44,45). Patient with predominantly NE or small cell carcinoma should be treated with cisplatin based chemotherapy (47).

Notes

• This provider combines search_papers_by_relevance with snippet_search.
• No synthesis or second-stage model call is performed.