Establishment of patient-derived tumor organoids to functionally inform treatment decisions in metastatic colorectal cancer

• DOI: 10.1016/j.esmoop.2023.101198
• Publication Date: 2023-04-27T05:06:53Z
• Authors: G. Martini; V. Belli; S. Napolitano; V. Ciaramella; D. Ciardiello; A. Belli; F. Izzo; A. Avallone; F. Selvaggi; F. Menegon Tasselli; W. Santaniello; R. Franco; I. Puig; L. Ramirez; I. Chicote; F. Mancuso; G. Caratu; X. Serres; R. Fasani; J. Jimenez; J. Ros; I. Baraibar; N. Mulet; C.M. Della Corte; T. Troiani; A. Vivancos; R. Dienstmann; E. Elez; H.G. Palmer; J. Tabernero; E. Martinelli; F. Ciardiello; G. Argilés
• Keywords: FOLFOX

Metastatic colorectal cancer (mCRC) patients tend to have modest benefits from molecularly driven therapeutics. Patient-derived tumor organoids (PDTOs) represent an unmatched model elucidate resistance therapy, due their high capacity resemble characteristics.We used viable tissue two cohorts of with mCRC, naïve or refractory treatment, respectively, for generating PDTOs. The derived models were subjected a 6-day drug screening assay (DSA) comprehensive pipeline chemotherapy and targeted drugs against almost all the actionable mCRC molecular drivers. For second cohort DSA data matched those PDTO genotyping.A total 40 PDTOs included in primary tumors metastases. first 31 treated front line. this cohort, results patient responses. Moreover, RAS/BRAF mutational status was cetuximab response. Ten out 12 (83.3%) RAS wild-type responded cetuximab, while mutant PDTOs, 8 (100%), resistant. (chemorefractory patients), we part genotyping. Four nine DSA/genotyping resulted applicable clinic. Two RAS-mutant been FOLFOX-bevacizumab mitomycin-capecitabine third line, based on results, obtaining disease control. One nivolumab-second mitochondrial-derived activator caspases mimetic (phase I trial) burden at genotyping, experiencing stable disease. In one case, presence BRCA2 mutation correlated sensitivity olaparib; however, could not receive therapy.Using CRC as model, designed validated clinically methodology potentially inform clinical decisions functional data. Undoubtedly, further larger analyses are needed improve success rates propose suitable treatment strategies patients.