Journal
CANCER DISCOVERY
Volume 11, Issue 7, Pages 1644-1660Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-20-1531
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Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) Investigator Grant [22802]
- AIRC 5 x 1000 grant [21091]
- AIRC/Cancer Research UK/FC AECC Accelerator Award [22795]
- H2020 grant [754923 COLOSSUS]
- Fondazione Piemontese per la Ricerca sul Cancro-ONLUS 5 x 1000 Ministero della Salute 2014
- Fondazione Piemontese per la Ricerca sul Cancro-ONLUS 5 x 1000 Ministero della Salute 2015
- Fondazione Piemontese per la Ricerca sul Cancro-ONLUS 5 x 1000 Ministero della Salute 2016
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Patient-derived models have played a crucial role in advancing the understanding of colorectal cancer biology, leading to the discovery of new therapeutic targets and mechanisms of drug resistance. These models have also influenced clinical decision-making by providing valuable insights into disease mechanisms and treatment responses.
Stratification of colorectal cancer into subgroups with different response to therapy was initially guided by descriptive associations between specific biomarkers and treatment outcome. Recently, preclinical models based on propagatable patient-derived tumor samples have yielded an improved understanding of disease biology, which has facilitated the functional validation of correlative information and the discovery of novel response determinants, therapeutic targets, and mechanisms of tumor adaptation and drug resistance. We review the contribution of patient-derived models to advancing colorectal cancer characterization, discuss their influence on clinical decision-making, and highlight emerging challenges in the interpretation and clinical transferability of results obtainable with such approaches. Significance: Association studies in patients with colorectal cancer have led to the identification of response biomarkers, some of which have been implemented as companion diagnostics for therapeutic decisions. By enabling biological investigation in a clinically relevant experimental context, patient-derived colorectal cancer models have proved useful to examine the causal role of such biomarkers in dictating drug sensitivity and are providing fresh knowledge on new actionable targets, dynamics of tumor evolution and adaptation, and mechanisms of drug resistance.
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