cisplatin

Overview

Cisplatin is a platinum-based alkylating agent that forms intrastrand and interstrand DNA crosslinks, inducing replication fork stalling and double-strand break (DSB) accumulation. It is one of the oldest and most widely used radiosensitizers: platinum adducts inhibit nucleotide-excision repair (NER), impairing the cell’s ability to resolve the DNA damage compounded by ionizing radiation. Cisplatin is part of definitive concurrent chemoradiation (CRT) regimens in head and neck squamous cell carcinoma (HNSCC), cervical cancer, and other epithelial malignancies, and remains the reference arm against which novel radiosensitizers and immunotherapy combinations are benchmarked.

Evidence in the corpus

The ROBIN GenRad HNSCC trial (NCT03521570, part 2) at Cleveland Clinic / Emory compared re-irradiation + cisplatin versus re-irradiation + immune checkpoint inhibitor (PD-1 inhibitor) in recurrent or second-primary HNSCC; this trial is described as completed at the time of the white paper. In that cohort, a 1.5-fold increase in PD1+Ki67+CD4+ T cells from baseline to week 2–4 correlated with shorter progression-free survival under re-irradiation + PD-1 blockade — findings that were interpreted in contrast to the cisplatin reference arm. PMID:41941260
The paper also references the Javelin HN100 chemoradiation ± avelumab expansion cohort (a cisplatin-backbone CRT trial) in the GenRad HNSCC context; analysis of that cohort identified intratumoral bacteria as a major source of therapy resistance in HNSCC, implicating the tumor microbiome as a resistance axis for CRT. PMID:41941260
Cisplatin-based CRT is used as background context for the METEOR center’s cervical cancer cohort, where CRT was found to remodel the TME with myeloid-cell infiltration and upregulation of the TP53/MDM2 axis in tumor cells, without significant upregulation of PD-L1/PD-1. PMID:41941260
In the UCLA sarcoma PDTO biobank (sarcoma_ucla_2024), cisplatin was a component of the MAP neoadjuvant regimen (methotrexate/doxorubicin/cisplatin) tested in three treatment-naïve osteosarcoma biopsies. Organoid residual viability after MAP correlated with post-resection necrosis and clinical outcome: two specimens with ~50–57% residual viability had 99% and 95% necrosis respectively (no recurrence at 1,400–1,500 days), while one specimen with 73% residual viability had only 60% necrosis and relapsed within 200 days. PMID:39305899
Cisplatin is also listed as a component of the >400-compound sarcoma PDTO screen and appears among the NCCN-listed standard-of-care regimens for osteosarcoma identified in the functional screen. PMID:39305899
In the phase 3 CALGB 90601 (NCT00942331) first-line metastatic urothelial carcinoma trial (gemcitabine/cisplatin ± bevacizumab), pretreatment cfDNA from 201 patients was assessed for DDR alterations and prognostic genomic features. Oncogenic DDR alterations including ERCC2 were not significantly associated with response to cisplatin-based chemotherapy (DDR+ response 50% vs DDR− 41%, p=0.4), primarily due to insufficient power (ERCC2 only 4.5%). Higher ctDNA VAF was independently associated with shorter OS on cisplatin-based therapy (HR 2.51, 95% CI 1.26–5.00; p=0.009). PMID:40256659
In the MSK PDAC cohort (pdac_msk_2024, n=1,480 with curated treatment data), FOLFIRINOX (oxaliplatin, not cisplatin) and gemcitabine/nab-paclitaxel were the dominant first-line regimens (38% and 37% respectively); cisplatin is mentioned as a historical reference in PDAC chemotherapy background. PMID:39753968
In preclinical HER2+ xenograft models, cisplatin was used as a comparator in cell viability assays; T-DM1 was more potent than cisplatin (and paclitaxel, trastuzumab, lapatinib, erlotinib) in HER2+ OE19 esophageal cancer cells, with T-DM1 IC50 <1 nM vs >100 nM in HER2− lines PMID:27698471.
Cohort-metadata context only: in the MD Anderson HNSCC imaging archive (n=215), 127 patients (59%) received concurrent chemotherapy, of whom 98% received platinum-based regimens (effectively cisplatin). No efficacy or biomarker claim is made; this citation records treatment-arm composition. PMID:30179230
Used as part of platinum-based chemotherapy for metastatic urothelial carcinoma in UC-GENOME (n=218 patients); ERCC2 mutations significantly associated with chemotherapy response (p=0.0134), validating this biomarker in the metastatic setting PMID:36333289
143 metastatic gallbladder carcinoma patients received gemcitabine/cisplatin as the predominant first-line chemotherapy regimen among 233 GBC cases profiled with MSK-IMPACT at MSK (2014–2021) PMID:36228155
Used as standard platinum-based chemotherapy in 100% of the 489 HGSOC patients in the TCGA ovarian carcinoma study; all patients received platinum-based therapy PMID:21720365
Referenced as part of standard chemoradiation regimens in HNSCC; the cBioPortal platform paper describes genomic data for patients treated with cisplatin-based protocols PMID:19176454
Cisplatin (with surgery and radiation) remains the standard-of-care backbone for OSCC at the time of the Pickering 2013 OSCC genomic analysis; no new biomarkers were validated for prospective treatment selection PMID:23619168
TCGA endometrial cancer analysis (2013) suggests ~25% of high-grade endometrioid tumors have a copy-number-high serous-like molecular phenotype and may benefit from chemotherapy regimens including cisplatin rather than adjuvant radiotherapy PMID:23636398
In muscle-invasive bladder carcinoma (n=131 BLCA), cisplatin-based chemotherapy was the reference standard of care at the time of the TCGA analysis with a median survival of 14–15 months for recurrent/metastatic disease; no molecularly targeted agent had been approved PMID:24476821
Cited in HCC trials (CELESTIAL, SHARP supporting context) as a reference comparator chemotherapy; sorafenib combinations not primary focus PMID:24798001
Platinum-based backbone (cisplatin + gemcitabine) is the standard chemotherapy platform for R/M NPC; sintilimab added to CCRT with cisplatin improved 36-mo EFS to 86% vs 76% (HR 0.59) PMID:24952746
Somatic ERCC2 mutations were found exclusively in cisplatin responders (9/25, 36%) in muscle-invasive urothelial carcinoma treated with neoadjuvant cisplatin-based chemotherapy; ERCC2 mutation is proposed as a predictive biomarker for cisplatin sensitivity PMID:25096233
Standard first-line therapy for advanced CCA (IHCH/EHCH/CHOL) in combination with gemcitabine, with durvalumab addition showing incremental benefit; BRCA1/2 mutations (~3–5% of CCA) predict platinum sensitivity PMID:25526346
Standard front-line platinum-based chemotherapy for gastric adenocarcinoma (STAD); BRCA2 mutation (17/294 cases, 5.8%) independently predicts longer survival (pooled HR 0.37, P=0.05) and may predict platinum and PARP-inhibitor sensitivity, paralleling ovarian cancer PMID:25583476
Referenced as a chemotherapy backbone for iCCA; futibatinib is cited as synergizing with cisplatin in FGFR2-rearranged iCCA PMID:25608663
Platinum chemotherapy; usable from second trimester in pregnant young-onset NSCLC patients; review notes TKIs and immunotherapy are contraindicated in pregnancy whereas platinum-based regimens are acceptable from T2 PMID:27346245
In head and neck cancer, germline FANCA deletion plus somatic FANCA stopgain in one HNSC patient identified as potential cisplatin-sensitivity biomarker by MSK-IMPACT profiling (N=151 advanced tumors) PMID:27442865
First-line platinum backbone in BEP (bleomycin+etoposide+cisplatin, 37.2%), EP (42.2%), and TIP/VIP (20%) regimens in 180 advanced GCT patients; TP53 alterations exclusive to cisplatin-resistant tumors (16.3% vs 0%; P<.001); nutlin-3 showed antiproliferative synergy with cisplatin in TP53 wild-type cisplatin-resistant GCT cell lines PMID:27646943
Cisplatin + gemcitabine (neoadjuvant/first-line) administered in the WashU urothelial carcinoma WES cohort (n=32 patients, 72 tumors); post-chemotherapy tumors showed clonal enrichment of L1CAM and integrin-signaling missense mutations, an APOBEC3A-dominant mutational signature, and selective elimination of ATM/RB1/FANCC-altered clones (73.3% pre- vs 37.9% post-chemotherapy, p=0.05); cisplatin specifically drove a C>A mutational signature consistent with its known adduct-forming mechanism PMID:27749842
Used in combination with etoposide (cisplatin/etoposide) as first-line chemotherapy in SCLC PDX models; 10/10 PDXs were sensitive to 6–8 cycles with 65–95% tumor growth inhibition; concurrent EZH2 inhibitor (EPZ011989) enhanced disease control and prevented SLFN11 suppression in SLFN11-high models PMID:28196596.
Adjuvant cisplatin/carboplatin plus vinorelbine was the standard adjuvant chemotherapy backbone in the TRACERx NSCLC ctDNA study (NCT01888601, n=24 longitudinal patients). ctDNA clearance after adjuvant therapy correlated with sustained remission (CRUK0013, 688 days relapse-free), while rising ctDNA SNV burden during adjuvant therapy identified resistance in real time in patients who all recurred within 1 year. PMID:28445469
Luminal-papillary MIBC (35% of TCGA bladder cohort, FGFR3-enriched) shows preliminary low likelihood of response to cisplatin-based neoadjuvant chemotherapy, while basal-squamous MIBC is proposed as appropriate for cisplatin-based regimens; etoposide-cisplatin is proposed for the neuronal subtype PMID:28988769
In 295 metastatic EGC patients (MSK-IMPACT), HRD/LST scores did not predict PFS on first-line platinum-based chemotherapy (HR=0.99, P=0.947); MSI-H patients had significantly shorter PFS on cytotoxic therapy (4.8 vs 6.9 months, HR=0.4, P=0.027) PMID:29122777

Resistance mechanisms

Intratumoral bacteria in HNSCC identified as a source of resistance to cisplatin-containing chemoradiation in the Javelin HN100 expansion cohort analysis (GenRad). PMID:41941260

Cancer types (linked)

HNSC — head and neck squamous cell carcinoma; standard concurrent CRT agent; GenRad comparator arm.
CESC — cervical cancer; concurrent CRT backbone in the METEOR cohort.
ESCA, STAD — HER2+ esophageal/gastric cancer; preclinical comparator context.
BLCA — metastatic urothelial carcinoma; CALGB 90601 backbone cisplatin-based chemotherapy; DDR alteration predictive value not confirmed (underpowered). WashU WES cohort (n=32): cisplatin + gemcitabine reshapes clonal architecture and drives APOBEC mutagenesis.
OS — osteosarcoma; MAP regimen component; organoid viability correlated with post-resection necrosis.
NSCLC — adjuvant cisplatin/carboplatin + vinorelbine backbone in TRACERx; ctDNA monitoring detected resistance and clearance in real time.

Sources

PMID:41941260 — Gregucci et al. 2026, Clin Cancer Res. ROBIN white paper; cisplatin discussed as radiosensitizer reference and CRT backbone in GenRad HNSCC and METEOR cervical cohorts.
PMID:27698471
PMID:30179230 — Grossberg et al. 2018, Sci Data. MD Anderson HNSCC imaging archive; cisplatin referenced as concurrent chemotherapy in 98% of the 127 chemo-treated patients (cohort-metadata only, no efficacy or biomarker claim).
PMID:39305899 — Al Shihabi et al. (Cell Stem Cell 2024). UCLA sarcoma PDTO biobank; MAP (methotrexate/doxorubicin/cisplatin) organoid viability correlated with post-resection necrosis in osteosarcoma.
PMID:39753968 — Varghese, Perry et al. (2024). MSK PDAC cohort; cisplatin referenced in chemotherapy background context.
PMID:40256659 — Guercio et al. (2025). CALGB 90601 cfDNA study; cisplatin-based chemotherapy backbone; DDR predictive value null (underpowered); VAF and TERT/PIK3CA/ERBB2 as prognostic markers.

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This page was processed by wiki-cli on 2026-05-14. - PMID:27646943 - PMID:27749842 — Faltas et al. 2016, Nature Genetics. WES of 72 UC tumors (32 patients); cisplatin + gemcitabine clonal evolution study; APOBEC3A enrichment and L1CAM/integrin clonal enrichment post-chemotherapy.

PMID:28445469 — Abbosh et al. 2017, Nature. TRACERx NSCLC ctDNA study; cisplatin/carboplatin + vinorelbine adjuvant chemotherapy; ctDNA clearance vs. resistance detected in real time.

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