docetaxel

Overview

Docetaxel is a semi-synthetic taxane that stabilizes microtubules, preventing depolymerization and inducing mitotic arrest and apoptosis. It is FDA-approved for breast, non-small-cell lung, prostate, gastric, and head and neck cancers, and is used off-label in combination with gemcitabine for sarcoma. In the UCLA sarcoma PDTO screen it was tested in the >400-compound panel.

Evidence in the corpus

  • In the UCLA sarcoma PDTO biobank (sarcoma_ucla_2024, n=194 specimens), gemcitabine + docetaxel was one of the matched regimens received by patients in the prospective correlation cohort (n=5 patients); normalized organoid viability correlated with time-to-next-treatment across the matched cohort (R²=0.921, p=0.009). PMID:39305899
  • Docetaxel was listed among NCCN-listed top-five regimens recurrently identified for osteosarcoma in the PDTO functional screen, alongside etoposide, cisplatin, sorafenib, regorafenib, doxorubicin, cabozantinib, gemcitabine, and everolimus. PMID:39305899
  • Used in combination with selumetinib in a co-clinical GEM/human trial for KRAS-mutant LUAD; STK11/LKB1 loss was found to significantly influence resistance to the selumetinib + docetaxel combination in mouse lung adenocarcinoma models PMID:23999436.
  • Most of 63 mCRPC men in the prad_fhcrc rapid-autopsy cohort received at least one systemic chemotherapy, most commonly docetaxel, as part of their prior treatment history; docetaxel use is described as a background treatment rather than a study intervention. PMID:26928463
  • Listed as a later-line regimen in the WashU urothelial carcinoma WES cohort (n=32 patients); specifically, docetaxel + ramucirumab was administered at disease progression in the WCM117 case after cisplatin + gemcitabine, illustrating the multi-line treatment context of post-chemotherapy clonal evolution PMID:27749842
  • Used in combination with gemcitabine (16 cycles) after nephrotoxicity precluded continuation of ISG/SSG IV protocol in EWSR1::BEND2 bladder sarcoma; disease was approximately stable on this regimen; patient died at 26 months post-diagnosis PMID:28199314.
  • Docetaxel-containing regimens were used as chemotherapy in the 295-patient metastatic EGC cohort (MSK-IMPACT); MSI-H patients had inferior PFS on cytotoxic therapy (4.8 vs 6.9 months, HR=0.4, P=0.027) and durable responses to immunotherapy instead PMID:29122777

Resistance mechanisms

  • Not specifically characterized in the sarcoma corpus.

Cancer types (linked)

  • OS — osteosarcoma; NCCN-listed indication in the PDTO screen context.
  • RMS — rhabdomyosarcoma; gemcitabine + docetaxel combination used in treatment-matched cohort.

Sources

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