| Target Gene Symbol | Target Name | Association Score | Key Evidence (approved drugs, clinical stage, relevant PMIDs) | Role in SCLC |
|---|---|---:|---|---|
| RB1 | RB transcriptional corepressor 1 | 0.73 | OpenTargets lists 5 supporting evidence items for MONDO_0008433, including literature PMIDs 34430610, 35792876, 26168399, 22941188, 24071849; recurrently identified as a defining SCLC tumor suppressor alteration (pqac-00000000, pqac-00000005) | Core tumor suppressor; near-universal functional loss helps drive cell-cycle deregulation and lineage transformation in SCLC (pqac-00000000, pqac-00000005) |
| TOP1 | DNA topoisomerase I | 0.65 | OpenTargets includes approval-stage evidence and clinical report IDs linked to TOP1-directed therapy plus regulatory records; literature and clinical evidence support topoisomerase-targeting treatment relevance in SCLC (pqac-00000000, pqac-00000014) | Therapeutic target class rather than lineage driver; relevant because SCLC is highly chemotherapy-sensitive initially and topoisomerase-directed agents are part of the treatment landscape, including irinotecan-based regimens and lurbinectedin-era development context (pqac-00000000, pqac-00000014) |
| TP53 | Tumor protein p53 | 0.63 | OpenTargets lists 5 evidence items including PMIDs 35340160, 37534137, 40113013, 30279957, 31737176; repeatedly described as nearly universal inactivation in SCLC (pqac-00000000, pqac-00000005) | Foundational tumor suppressor loss; with RB1 inactivation it is a hallmark initiating event in most SCLC and underlies genomic instability, apoptosis evasion, and aggressive behavior (pqac-00000000, pqac-00000005) |
| CD274 (PD-L1) | CD274 molecule | 0.62 | OpenTargets includes 5 literature-backed evidence items (PMIDs 32773010, 39810133, 38132164, 37040387, 31315783); clinical use supported by atezolizumab and durvalumab with platinum-etoposide in ES-SCLC (pqac-00000000, pqac-00000017, pqac-00000019) | Immune checkpoint target; PD-L1-axis blockade is part of current first-line standard therapy for extensive-stage SCLC, though benefits are modest and biomarker performance is imperfect (pqac-00000017, pqac-00000019) |
| CDK6 | Cyclin dependent kinase 6 | 0.62 | OpenTargets lists literature PMIDs 39136283 and 35117162 plus approval/phase 4 evidence; CDK4/6 dependency is most relevant in RB1-retained subsets (pqac-00000000) | Cell-cycle kinase target; may represent an actionable vulnerability in uncommon RB1-proficient SCLC tumors rather than classic RB1-null disease (pqac-00000000) |
| CDK4 | Cyclin dependent kinase 4 | 0.59 | OpenTargets lists literature PMIDs 39136283 and 31199581 plus approval/phase 4 evidence; CDK4/6 inhibitor sensitivity has been linked to RB1-expressing SCLC subsets (pqac-00000000) | Similar to CDK6, supports a precision-medicine niche in RB1-intact SCLC, where CDK4/6 blockade may suppress tumor growth (pqac-00000000) |
| DLL3 | Delta like canonical Notch ligand 3 | 0.59 | OpenTargets includes literature PMIDs 38468968, 41331586, 31819500, 31452726 and approval-stage evidence; DLL3-targeted BiTE therapy tarlatamab is highlighted in recent SCLC therapeutic reviews and trials (pqac-00000000, pqac-00000015, pqac-00000016) | Lineage-associated surface antigen enriched in neuroendocrine SCLC; major emerging therapeutic target for bispecific T-cell engagers, ADCs, and CAR-T approaches (pqac-00000015, pqac-00000016) |
| TOP2A | DNA topoisomerase II alpha | 0.58 | OpenTargets includes literature PMIDs 38806610, 37407689, 39921782 plus approval-stage evidence; mechanistically relevant to etoposide-based therapy backbone in SCLC (pqac-00000000, pqac-00000014) | Cytotoxic therapy target linked to the etoposide backbone of standard treatment; reflects persistent dependence of SCLC management on DNA damage and topoisomerase-directed chemotherapy (pqac-00000000, pqac-00000014) |


*Table: This table summarizes the leading OpenTargets disease-target associations for small cell lung cancer (MONDO_0008433) and links them to their clinical or biological roles in SCLC. It is useful for distinguishing foundational drivers such as TP53/RB1 from actionable therapeutic targets such as PD-L1, DLL3, CDK4/6, and topoisomerases.*