Quantitative proteomics of antibody-drug conjugates and chemotherapy targets in prostate cancer (AACR 2023)
Chemotherapy involves the use of anti-tubulins (docetaxel, cabazitaxel), platinum salts, and topoisomerase inhibitors (TOPO1, TOPO2A)...Biomarkers of resistance include ERCC1 (Platinum), TUBB3 (taxanes), ALDH1A1 (cyclophosphamide), while response biomarkers include TOPO1 (irinotecan, topotecan), TOPO2A (doxorubicin, epirubicin), and hENT1 (Gemcitabine)...ERCC1, a marker for resistance to platinum-based agents, was not detected in 26% of cases, potentially enabling a cisplatin/carboplatin-based regimen in 1/4th of prostate cancer patients...These include doxorubicin biomarker TOPO2A in 34% of cases with 10x range, gemcitabine biomarker hENT1 in 36% of cases (4x range), temozolomide biomarker MGMT (ND in 12% of cases)...Trop2 was quantitated in 93% of the cases and had wide range of 37x (437 -16267 amol/ µg). The capacity to multiplex 72 protein biomarkers from 2-3 FFPE sections yields a wealth of actionable information for clinical treatment or patient stratification in clinical trials.