NRAS Mutant Melanoma

1. Disease Information

1.1 Concise overview

NRAS-mutant melanoma is a molecular subset of melanoma (most often cutaneous melanoma in the available evidence) characterized by activating somatic mutations in NRAS, a small GTPase that drives constitutive downstream signaling—most prominently MAPK (RAF–MEK–ERK) and frequently PI3K–AKT pathway activity—leading to increased proliferation and survival. In contemporary clinical practice, it is recognized as a therapeutically important subgroup because (i) it represents ~15–20% of melanomas, (ii) direct mutant-NRAS inhibitors have historically been lacking, and (iii) treatment is typically centered on immune checkpoint blockade with targeted therapy options being limited and/or modest in efficacy. (phadke2023targetingnrasmutationsinadvanced pages 1-2, braud2023initialevidencefor pages 1-3)

A key molecular feature is that the predominant NRAS mutations in melanoma occur at codon 61 (Q61), which impair intrinsic GTPase activity and keep NRAS in a GTP-bound “ON” state. (phadke2023targetingnrasmutationsinadvanced pages 1-2, zhao2021novelinsightsinto pages 3-4)

1.2 Key identifiers and cross-references

The retrieved literature did not provide canonical disease identifiers (ICD-10/ICD-11, MeSH, OMIM, Orphanet, MONDO) specifically for the molecular subtype “NRAS-mutant melanoma.” The Open Targets search returned broader melanoma concepts (e.g., melanoma and cutaneous melanoma) with evidence linked to NRAS, but not a dedicated “NRAS-mutant melanoma” MONDO identifier in the retrieved outputs. (phadke2023targetingnrasmutationsinadvanced pages 1-2, braud2023initialevidencefor pages 1-3)

Ontology summary artifact:

Table: This table maps the disease naming used in the retrieved evidence for NRAS-mutant melanoma and related parent concepts. It is useful for ontology normalization because the retrieved sources support the molecular subtype terminology but did not provide a dedicated MONDO/MeSH/ICD identifier for the subtype itself.

1.3 Synonyms / alternative names

Commonly used synonyms in the literature include: - “NRAS-mutant melanoma” / “NRAS-mutated melanoma” (phadke2023targetingnrasmutationsinadvanced pages 1-2, braud2023initialevidencefor pages 1-3) - “NRAS Q61-mutant melanoma” and variant-specific groupings such as “NRAS Q61R/K/L melanoma” (phadke2023targetingnrasmutationsinadvanced pages 1-2, murphy2022enhancedbrafengagement pages 1-2)

1.4 Evidence source type

The retrieved evidence is primarily: - Aggregated disease-level resources (systematic review/meta-analysis of immunotherapy response) (jaeger2023objectiveresponseto pages 1-2) - Prospective/retrospective human cohorts for clinicopathologic correlations and outcomes (devitt2011clinicaloutcomeand pages 1-3, haugh2024targeteddnasequencing pages 1-2) - Interventional clinical trials for targeted therapy combinations (braud2023initialevidencefor pages 1-3, queirolo2017binimetinibforthe pages 9-11) - Genetically engineered mouse models (GEMMs) and mechanistic studies (burd2014mutationspecificrasoncogenicity pages 1-3, murphy2022enhancedbrafengagement pages 1-2, johanna2021epigeneticcontrolof pages 1-2, yang2023cxcr2expressionduring pages 1-2)

2. Etiology

2.1 Disease causal factors

Genetic (somatic) driver: Activating somatic mutations in NRAS are a central causal factor defining the subtype. NRAS mutations are reported in ~15–20% of melanomas in multiple sources. (phadke2023targetingnrasmutationsinadvanced pages 1-2, braud2023initialevidencefor pages 1-3)

Hotspot biology: A 2023 JCO review states that the predominant alterations (>80%) occur at codon 61 (Q61R, Q61L, Q61K) and “serve to impair GTPase activity, locking the gene in a constitutively ON position.” (phadke2023targetingnrasmutationsinadvanced pages 1-2)

2.2 Risk factors

Tumor/pathology-associated “risk correlates” for NRAS-mutant status (not necessarily causal exposures): - In a prospective cohort, NRAS-mutant primary cutaneous melanomas were associated with greater thickness and higher mitotic activity: “Seventy-five percentage of NRAS mutations occurred in tumors >1 mm thick …” and “Twenty-seven (75%) tumors with NRAS mutations had a mitotic count of >1/mm2 … (P = 0.001).” (devitt2011clinicaloutcomeand pages 1-3) - NRAS mutations were enriched in nodular melanoma in this cohort: “9 (25%) of all NRAS mutations occurring in this subtype (P < 0.001).” (devitt2011clinicaloutcomeand pages 1-3)

Ultraviolet (UV) exposure and chronic sun damage (CSD): Evidence in retrieved sources is mixed depending on the study design and definition. - Devitt et al. reported: “There was no association between chronic sun damage and NRAS mutations.” (devitt2011clinicaloutcomeand pages 1-3) - A 2024 targeted-sequencing cohort notes a molecular classification context where “BRAF and NRAS mutant melanomas correlate with low cumulative sun damage (low-CSD), while NF1 mutants are high-CSD.” (haugh2024targeteddnasequencing pages 1-2)

Given these differences, UV is clearly etiologic for cutaneous melanoma broadly, but the specific relationship between chronic sun damage patterns and NRAS-mutant subtype varies across cohorts and should be represented as heterogeneous evidence rather than a single settled association. (devitt2011clinicaloutcomeand pages 1-3, haugh2024targeteddnasequencing pages 1-2)

2.3 Protective factors

No genotype-specific protective factors were identified in the retrieved sources.

2.4 Gene–environment interactions

Direct gene–environment interaction evidence specific to NRAS-mutant melanoma was not identified in the retrieved sources (beyond the broader context that UV contributes to melanoma mutagenesis and that NRAS hotspot variants are selected by functional constraints). (murphy2022enhancedbrafengagement pages 1-2)

3. Phenotypes

3.1 Clinical and pathological phenotype spectrum

NRAS-mutant melanoma generally presents clinically as cutaneous melanoma, with pathological correlates that may indicate a more aggressive primary tumor phenotype in multiple cohorts.

From Devitt et al. (prospective cohort): - Greater tumor thickness: “Seventy-five percentage of NRAS mutations occurred in tumors >1 mm thick …” (devitt2011clinicaloutcomeand pages 1-3) - Higher mitotic activity: “Twenty-seven (75%) tumors with NRAS mutations had a mitotic count of >1/mm2 … (P = 0.001).” (devitt2011clinicaloutcomeand pages 1-3) - Nodular enrichment: “9 (25%) of all NRAS mutations occurring in this subtype (P < 0.001).” (devitt2011clinicaloutcomeand pages 1-3)

3.2 Onset, severity, progression

Specific age-of-onset distributions for the NRAS-mutant subgroup were not extracted from the retrieved evidence. However, the subgroup is repeatedly described as clinically challenging and (in multiple sources) as associated with poorer prognosis than NRAS-wildtype melanoma. (braud2023initialevidencefor pages 1-3, jaeger2023objectiveresponseto pages 1-2)

3.3 Quality of life impact

NRAS-mutant melanoma–specific quality-of-life measures were not identified in the retrieved sources.

3.4 Suggested HPO terms (phenotype representation suggestions)

These are suggested to structure typical melanoma features and aggressive primary features described above: - Cutaneous melanoma / malignant melanoma: no single HPO term asserted here from evidence; use clinical coding per knowledge base conventions - Increased mitotic activity: HP:0010644 (Increased mitotic activity) (maps to the cohort observation of higher mitotic count) (devitt2011clinicaloutcomeand pages 1-3) - Increased tumor thickness (Breslow): represent as a quantitative pathology attribute (no specific HPO term was retrieved in evidence) - Nodular melanoma subtype: represent as histologic subtype attribute (not strictly an HPO term)

4. Genetic / Molecular Information

4.1 Causal gene

• NRAS (NRAS proto-oncogene, GTPase) is the defining causal driver gene for the subtype. (phadke2023targetingnrasmutationsinadvanced pages 1-2, braud2023initialevidencefor pages 1-3)

4.2 Pathogenic variants (somatic)

Hotspots: Codon 61 is dominant. - 2023 JCO review: predominant alterations (>80%) at codon 61 (Q61R, Q61L, Q61K). (phadke2023targetingnrasmutationsinadvanced pages 1-2) - 2021 review excerpt: “The majority (~84%) of NRAS mutations occur at codon 61.” (zhao2021novelinsightsinto pages 3-4)

Functional consequence: Gain-of-function with impaired GTPase activity and increased signaling output. - Direct quote: codon 61 variants “serve to impair GTPase activity, locking the gene in a constitutively ON position.” (phadke2023targetingnrasmutationsinadvanced pages 1-2)

4.3 Key downstream pathways and cellular programs

NRAS activation drives multiple signaling cascades. - Devitt et al.: “NRAS ... leads to upregulation of the MAPK pathway, the phosphatidylinositol 3¢ kinase (PI3K) pathway and the RAL pathway.” (devitt2011clinicaloutcomeand pages 1-3) - Phadke & Smalley emphasize strong MAPK activation and note NRAS-mutant melanomas signal via CRAF rather than BRAF (mechanistic framing in the excerpt). (phadke2023targetingnrasmutationsinadvanced pages 1-2)

4.4 Modifier genes / co-alterations (treatment-relevant)

A practical treatment-relevant modifier concept is cell-cycle gene co-alteration. - In the ribociclib+binimetinib trial, response was higher in tumors with NRAS mutation plus concurrent alterations in CDKN2A/CDK4/CCND1 (ORR 32.5% in that subgroup). (braud2023initialevidencefor pages 1-3)

4.5 Epigenetic information

A NRASQ61K;Cdkn2a−/− GEMM study links epigenetic regulation to invasiveness via SALL4 and HDAC2. - “SALL4 negatively regulates invasiveness through interaction with the histone deacetylase (HDAC) 2 …” and “SALL4 loss induces a phenotype switch and the acquisition of an invasive phenotype.” (johanna2021epigeneticcontrolof pages 1-2)

4.6 Suggested ontology terms (GO/Reactome-style; representation suggestions)

Based on pathways explicitly described in evidence: - GO:0000165 (MAPK cascade) — supported by MAPK upregulation statements (devitt2011clinicaloutcomeand pages 1-3) - GO:0014065 (phosphatidylinositol 3-kinase signaling) — supported by PI3K pathway mention (devitt2011clinicaloutcomeand pages 1-3) - GO:0007264 (small GTPase mediated signal transduction) — aligns with NRAS biology (phadke2023targetingnrasmutationsinadvanced pages 1-2)

5. Environmental Information

The retrieved sources did not provide detailed environmental exposure quantification specific to NRAS-mutant melanoma beyond the mixed findings regarding chronic sun damage patterns in relation to NRAS-mutant status. (devitt2011clinicaloutcomeand pages 1-3, haugh2024targeteddnasequencing pages 1-2)

6. Mechanism / Pathophysiology

6.1 Causal chain (high-level)

1) Somatic NRAS activating mutation (most commonly codon 61) impairs GTPase activity, increasing the fraction of NRAS in the active GTP-bound state. (phadke2023targetingnrasmutationsinadvanced pages 1-2, burd2014mutationspecificrasoncogenicity pages 1-3) 2) Active NRAS drives downstream signaling through MAPK and other cascades (PI3K, RAL), increasing proliferation and survival. (devitt2011clinicaloutcomeand pages 1-3) 3) Additional cooperating alterations (e.g., loss of cell-cycle checkpoints such as Cdkn2a/INK4a in experimental models; cell-cycle co-alterations in human tumors) promote tumor initiation/progression and influence therapeutic vulnerabilities. (burd2014mutationspecificrasoncogenicity pages 1-3, braud2023initialevidencefor pages 1-3)

6.2 Codon-specific selection and RAF engagement (mechanistic advances)

Mechanistic work supports that melanoma-enriched NRAS Q61 variants have properties that favor melanoma initiation. - Burd et al. (2014) found NRASQ61R is melanomagenic in vivo (especially with p16INK4a/Cdkn2a loss) while NRASG12D is not, and that enhanced GTP-bound state and stability contribute to oncogenicity. (burd2014mutationspecificrasoncogenicity pages 1-3) - Murphy et al. (2022) used an allelic series of endogenous Nras knock-in models and report that common melanoma-associated Q61 mutants (Q61R, Q61K, Q61L) are potent drivers, and provide a mechanistic basis: melanomagenic Q61 mutants enhance BRAF binding and BRAF–CRAF dimer formation, increasing MAPK→ERK signaling. (murphy2022enhancedbrafengagement pages 1-2)

6.3 Immune microenvironment involvement (preclinical)

In an NRasQ61R/Ink4a−/− GEMM, modulating CXCR2 altered tumor induction and anti-tumor immunity. - Genetic or pharmacologic inhibition of CXCR2 during induction “reduced tumor incidence/growth and increased anti-tumor immunity,” with mechanistic correlates including altered transcriptional programs and reduced AKT/mTOR activation. (yang2023cxcr2expressionduring pages 1-2)

6.4 Suggested Cell Ontology (CL) terms (representation suggestions)

• CL:0000542 (lymphocyte) and CL:0000624 (CD8-positive, alpha-beta T cell) — relevant given anti-tumor immunity and CD8+ involvement described in mouse immunology context (yang2023cxcr2expressionduring pages 1-2)
• CL:0000235 (macrophage) — relevant to tumor immune microenvironment modulation studies (yang2023cxcr2expressionduring pages 1-2)

7. Anatomical Structures Affected

7.1 Organ/tissue level

NRAS-mutant melanoma in the retrieved evidence is largely discussed in the context of cutaneous melanoma with primary lesions in the skin and metastatic spread typical of melanoma (not systematically enumerated in the retrieved sources). (devitt2011clinicaloutcomeand pages 1-3, haugh2024targeteddnasequencing pages 1-2)

Suggested UBERON terms (representation suggestions): - UBERON:0002097 (skin of body) - UBERON:0000955 (brain) may be relevant for melanoma metastasis generally, but brain-metastasis-specific NRAS-mutant data were not retrieved here.

8. Temporal Development

Temporal staging/progression patterns specific to NRAS-mutant melanoma were not explicitly extracted from the retrieved sources beyond associations with primary tumor aggressiveness markers (thickness, mitotic rate) and worsened survival metrics in some cohorts. (devitt2011clinicaloutcomeand pages 1-3, haugh2024targeteddnasequencing pages 1-2)

9. Inheritance and Population

9.1 Epidemiology

The retrieved sources did not provide population incidence/prevalence for NRAS-mutant melanoma as a distinct entity. However, multiple sources converge that NRAS mutations occur in ~15–20% of melanomas, which can be used as an approximate subtype fraction among melanoma cases. (phadke2023targetingnrasmutationsinadvanced pages 1-2, braud2023initialevidencefor pages 1-3)

9.2 Inheritance

NRAS-mutant melanoma is primarily defined by somatic tumor mutations rather than a Mendelian inherited pattern in the retrieved evidence. (phadke2023targetingnrasmutationsinadvanced pages 1-2)

10. Diagnostics

10.1 Standard diagnostic approach (as supported in retrieved evidence)

The key diagnostic discriminator for this subtype is tumor genomic testing (targeted NGS panels or hotspot assays) to identify NRAS driver mutations. - A 2024 clinical cohort explicitly uses molecular grouping of cutaneous melanoma into “BRAF mutant, NRAS mutant, NF1 loss, and triple wild type (TWT).” (haugh2024targeteddnasequencing pages 1-2)

10.2 Biomarkers and molecular stratification

• NRAS mutation status (particularly codon 61) is the defining biomarker. (phadke2023targetingnrasmutationsinadvanced pages 1-2, zhao2021novelinsightsinto pages 3-4)
• Tumor mutational burden (TMB) may be predictive for benefit from dual checkpoint blockade in melanoma broadly: in one cohort, “Elevated TMB correlated with improved progression-free survival on combination checkpoint inhibition (anti-PD1 plus anti-CTLA4).” (haugh2024targeteddnasequencing pages 1-2)

10.3 Suggested diagnostic ontology terms (representation suggestions)

• MAXO:0000136 (tumor genomic sequencing / next-generation sequencing) — suggested for molecular classification workflows (haugh2024targeteddnasequencing pages 1-2)

11. Outcome / Prognosis

NRAS mutation status has been associated with worse prognosis in multiple contexts, though effects can vary by cohort and treatment era.

• Devitt et al. reported NRAS mutations were independently associated with worse melanoma-specific survival: “(hazard ratio (HR) 2.96; P = 0.04).” (devitt2011clinicaloutcomeand pages 1-3)
• In a 2024 cohort (n=254), “NRAS mutant melanoma demonstrated significantly decreased overall survival on multivariable analysis (HR for death 2.95, 95% CI 1.13–7.69, p = 0.027).” (haugh2024targeteddnasequencing pages 1-2)

These findings support representing NRAS mutation as an adverse prognostic factor in at least some clinical populations, while noting that immunotherapy response may be comparable or better than NRAS-wildtype based on pooled response analyses (below). (haugh2024targeteddnasequencing pages 1-2, jaeger2023objectiveresponseto pages 1-2)

12. Treatment

12.1 Current standard-of-care and real-world implementation

The retrieved sources consistently position immune checkpoint inhibitors (ICIs) as the mainstay systemic therapy for advanced/metastatic NRAS-mutant melanoma, in the absence of an approved direct NRAS inhibitor. (phadke2023targetingnrasmutationsinadvanced pages 1-2, braud2023initialevidencefor pages 1-3)

Evidence synthesis for ICI response by genotype: - Systematic review/meta-analysis (Frontiers in Medicine, Feb 2023): pooled data from 1,770 patients found NRAS-mutant melanoma had a higher likelihood of objective response compared with NRAS-wildtype, effect size 1.28 (95% CI 1.01–1.64). (jaeger2023objectiveresponseto pages 1-2)

12.2 Targeted therapies and combinations (key trials)

No approved targeted therapy for NRAS-mutant melanoma is asserted in the retrieved JCO sources; MEK inhibition has modest activity and is a common development backbone. (phadke2023targetingnrasmutationsinadvanced pages 1-2, braud2023initialevidencefor pages 1-3)

Binimetinib (MEK inhibitor), NEMO trial benchmark: - Reported outcomes (as summarized in retrieved sources): median PFS 2.8 vs 1.5 months (binimetinib vs dacarbazine; HR 0.62), ORR ~15% vs 7%, median OS 11.0 vs 10.1 months (no OS benefit). (queirolo2017binimetinibforthe pages 9-11) - Notable tolerability issues included higher discontinuation for toxicity (25% vs 8%) and frequent dose reductions/interruptions. (queirolo2017binimetinibforthe pages 9-11)

Naporafenib (RAF inhibitor) + trametinib (MEK inhibitor): - In the JCO 2023 expansion arm, ORR reached 46.7% (7/15) at naporafenib 200 mg BID + trametinib 1 mg daily with median PFS 5.52 months; a higher-dose naporafenib cohort had lower ORR (13.3%). (braud2023initialevidencefor pages 1-3)

Ribociclib (CDK4/6 inhibitor) + binimetinib: - Phase Ib/II: ORR 19.5% (8/41) at RP2D; ORR 32.5% in tumors with concurrent CDKN2A/CDK4/CCND1 alterations; median PFS 3.7 months; median OS 11.3 months. (braud2023initialevidencefor pages 1-3)

Treatment evidence artifact (trial summary table):

Table: This table summarizes major therapeutic evidence in NRAS-mutant melanoma, including benchmark trial outcomes for MEK inhibition, emerging targeted combinations, and pooled immunotherapy response data. It is useful for comparing efficacy, toxicity, and clinical positioning of the main evidence-supported approaches.

12.3 Suggested MAXO terms (treatment representation suggestions)

• Immune checkpoint inhibitor therapy (anti–PD-1 / anti–CTLA-4): MAXO terms depend on the ontology version used in the knowledge base; represent as “immune checkpoint blockade” supported as standard care (phadke2023targetingnrasmutationsinadvanced pages 1-2, jaeger2023objectiveresponseto pages 1-2)
• MEK inhibitor therapy: supported by NEMO and other MEK-inhibitor trials (queirolo2017binimetinibforthe pages 9-11)
• Combined RAF/MEK inhibition (nMRAS context: naporafenib+trametinib investigational): (braud2023initialevidencefor pages 1-3)
• CDK4/6 inhibitor + MEK inhibitor combination: (braud2023initialevidencefor pages 1-3)

13. Prevention

No NRAS-mutant–specific prevention strategies were identified in the retrieved sources. Prevention and screening would generally follow cutaneous melanoma recommendations (UV exposure reduction, skin surveillance), but genotype-specific prevention claims cannot be made from the retrieved evidence set.

14. Other Species / Natural Disease

Not addressed in retrieved sources.

15. Model Organisms

NRAS-mutant melanoma has multiple well-established genetically engineered mouse models used to study initiation, progression, metastasis, and immune regulation.

15.1 Key GEMMs and what they show

• Endogenous conditional Nras Q61 allelic series (Tyr::CreERT2 activation; neonatal UVB cooperation): Q61R, Q61K, Q61L are strong melanoma drivers with high penetrance; Q61P/Q61Q are not, and melanomagenic variants enhance BRAF engagement and BRAF–CRAF dimerization to increase ERK signaling. (murphy2022enhancedbrafengagement pages 1-2)
• N-RasQ61R knock-in with Cdkn2a/p16INK4a loss: Efficiently promotes melanoma in vivo, whereas N-RasG12D does not; supports codon-61 selection and the relevance of Q61 models for human NRAS-mutant melanoma. (burd2014mutationspecificrasoncogenicity pages 1-3)
• Tyr::NrasQ61K; Cdkn2a−/− model in epigenetic invasiveness study: Sall4 is re-expressed and “its expression is necessary for primary melanoma formation,” while Sall4 loss promotes micrometastases and induces an invasive phenotype via HDAC2-linked regulation. (johanna2021epigeneticcontrolof pages 1-2)
• NRasQ61R/Ink4a−/− model in immune microenvironment modulation: CXCR2 loss/inhibition during tumor induction reduces tumor incidence/growth and increases anti-tumor immunity, with associated transcriptional and signaling changes (including reduced AKT/mTOR activation). (yang2023cxcr2expressionduring pages 1-2)

15.2 Model limitations (from retrieved evidence)

Explicit limitations were not systematically discussed in the retrieved excerpts; however, several studies highlight that codon-specific biology and cooperating tumor suppressor contexts can strongly affect phenotype, emphasizing the need to match model genotype to the human tumor context (e.g., Cdkn2a/Ink4a loss, UV exposure paradigms). (burd2014mutationspecificrasoncogenicity pages 1-3, murphy2022enhancedbrafengagement pages 1-2)

Recent Developments and “Latest Research” (prioritizing 2023–2024 in retrieved sources)

1) Targeting strategies remain an unmet need; direct NRAS inhibitors historically lacking: The 2023 JCO review emphasizes the lack of equivalent targeted inhibitors for mutant NRAS in melanoma and focuses on pathway targeting and emerging strategies. (phadke2023targetingnrasmutationsinadvanced pages 1-2)

2) Genotype–immunotherapy response synthesis: A 2023 systematic review/meta-analysis (Frontiers in Medicine; Feb 2023) pooled 10 studies/1,770 patients and found improved objective response likelihood for NRAS-mutant vs NRAS-wildtype melanoma (effect size 1.28). (jaeger2023objectiveresponseto pages 1-2)

3) Emerging targeted combinations with higher response signals: The 2023 JCO phase Ib expansion arm for naporafenib+trametinib reported ORR 46.7% in one dosing cohort, supporting ongoing randomized development. (braud2023initialevidencefor pages 1-3)

4) Clinicogenomic outcome stratification in routine practice cohorts: A 2024 cohort integrating targeted NGS and follow-up reported NRAS-mutant cutaneous melanoma had significantly worse overall survival (multivariable HR ~2.95) and that higher TMB predicted longer PFS on dual checkpoint blockade. (haugh2024targeteddnasequencing pages 1-2)

Evidence gaps relative to the requested template (not found in retrieved sources)

• MONDO/MeSH/ICD identifiers specific to the “NRAS-mutant melanoma” subtype were not retrieved.
• Population-level incidence/prevalence statistics (e.g., SEER rates) were not retrieved.
• Detailed differential diagnosis and histopathology/IHC marker panels were not retrieved.
• NRAS-mutant–specific prevention and screening guidelines were not retrieved.

URLs and publication dates (from retrieved evidence)

• Phadke MS, Smalley KSM. Journal of Clinical Oncology. May 2023. DOI: https://doi.org/10.1200/JCO.23.00205 (phadke2023targetingnrasmutationsinadvanced pages 1-2)
• de Braud F et al. Journal of Clinical Oncology. May 2023. DOI: https://doi.org/10.1200/JCO.22.02018 (braud2023initialevidencefor pages 1-3)
• Jaeger ZJ et al. Frontiers in Medicine. Feb 2023. DOI: https://doi.org/10.3389/fmed.2023.1090737 (jaeger2023objectiveresponseto pages 1-2)
• Devitt B et al. Pigment Cell & Melanoma Research. Aug 2011. DOI: https://doi.org/10.1111/j.1755-148X.2011.00873.x (devitt2011clinicaloutcomeand pages 1-3)
• Haugh AM et al. Cancers. Jan 2024. DOI: https://doi.org/10.3390/cancers16071347 (haugh2024targeteddnasequencing pages 1-2)
• Murphy BM et al. Nature Communications. Jun 2022. DOI: https://doi.org/10.1038/s41467-022-30881-9 (murphy2022enhancedbrafengagement pages 1-2)
• Burd CE et al. Cancer Discovery. Dec 2014. DOI: https://doi.org/10.1158/2159-8290.CD-14-0729 (burd2014mutationspecificrasoncogenicity pages 1-3)
• Diener J et al. Nature Communications. Aug 2021. DOI: https://doi.org/10.1038/s41467-021-25326-8 (johanna2021epigeneticcontrolof pages 1-2)
• Yang J et al. Molecular Cancer. Jun 2023. DOI: https://doi.org/10.1186/s12943-023-01789-9 (yang2023cxcr2expressionduring pages 1-2)
• Queirolo P, Spagnolo F. Expert Review of Anticancer Therapy. Sep 2017. DOI: https://doi.org/10.1080/14737140.2017.1374177 (queirolo2017binimetinibforthe pages 9-11)

References

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