Circulating Tumor DNA to Drive Treatment in Metastatic Colorectal Cancer.

Abstract

In the evolving molecular treatment landscape of metastatic colorectal cancer (mCRC), the identification of druggable alterations is pivotal to achieve the best therapeutic opportunity for each patient. Because the number of actionable targets is expanding, there is the need to timely detect their presence or emergence to guide the choice of different available treatment options. Liquid biopsy, through the analysis of circulating tumor DNA (ctDNA), has proven safe and effective as a complementary method to address cancer evolution while overcoming the limitations of tissue biopsy. Even though data are accumulating regarding the potential for ctDNA-guided treatments applied to targeted agents, still major gaps in knowledge exist as for their application to different areas of the continuum of care. In this review, we recapitulate how ctDNA information could be exploited to drive different targeted treatment strategies in mCRC patients, by refining molecular selection before treatment by addressing tumor heterogeneity beyond tumor tissue biopsy; longitudinally monitoring early-tumor response and resistance mechanisms to targeted agents, potentially leading to tailored, molecular-driven, therapeutic options; guiding the molecular triage towards rechallenge strategies with anti-EGFR agents, suggesting the best time for retreatment; and providing opportunities for an "enhanced rechallenge" through additional treatments or combos aimed at overcoming acquired resistance. Besides, we discuss future perspectives concerning the potential role of ctDNA to fine-tune investigational strategies such as immuno-oncology.

• Authors: Giorgio Patelli, Gianluca Mauri, Federica Tosi, Alessio Amatu, Katia Bencardino, Erica Bonazzina, Elio Gregory Pizzutilo, Federica Villa, Gabriele Calvanese, Alberto Giuseppe Agostara, Stefano Stabile, Silvia Ghezzi, Giovanni Crisafulli, Federica Di Nicolantonio, Silvia Marsoni, Alberto Bardelli, Salvatore Siena, Andrea Sartore-Bianchi
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 29 Issue 22 Pg. 4530-4539 (Nov 14 2023) ISSN: 1557-3265 [Electronic] United States
• PMID: 37436743 (Publication Type: Review, Journal Article)
• Copyright: ©2023 The Authors; Published by the American Association for Cancer Research.

Chemical References

• Circulating Tumor DNA
• Antineoplastic Agents
• Biomarkers, Tumor

Topics

• Humans
• Circulating Tumor DNA (genetics)
• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Colonic Neoplasms (drug therapy)
• Rectal Neoplasms (drug therapy)
• Antineoplastic Agents (therapeutic use)
• Biomarkers, Tumor (genetics, therapeutic use)