Precision oncology in metastatic colorectal cancer - from biology to medicine

Remarkable progress has been made in the development of biomarker-driven targeted therapies for patients with multiple cancer types, including melanoma, breast and lung tumours, although precision oncology for patients with colorectal cancer (CRC) continues to lag behind. Nonetheless, the availabili...

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Published in:Nature reviews. Clinical oncology Vol. 18; no. 8; pp. 506 - 525
Main Authors: Di Nicolantonio, Federica, Vitiello, Pietro Paolo, Marsoni, Silvia, Siena, Salvatore, Tabernero, Josep, Trusolino, Livio, Bernards, Rene, Bardelli, Alberto
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.08.2021
Subjects:
Animals
Biology
Breast cancer
Clinical trials
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - pathology
Colorectal Neoplasms - therapy
Evidence-Based Medicine - methods
Evidence-Based Medicine - trends
Humans
Lung cancer
Melanoma
Metastases
Metastasis
Neoplasm Metastasis
Oncology
Patients
Precision medicine
Precision Medicine - methods
Precision Medicine - trends
Solid tumors
Translational Research, Biomedical - methods
Translational Research, Biomedical - trends
Tumors
ISSN:1759-4774, 1759-4782, 1759-4782
Online Access:Get full text
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Summary:Remarkable progress has been made in the development of biomarker-driven targeted therapies for patients with multiple cancer types, including melanoma, breast and lung tumours, although precision oncology for patients with colorectal cancer (CRC) continues to lag behind. Nonetheless, the availability of patient-derived CRC models coupled with in vitro and in vivo pharmacological and functional analyses over the past decade has finally led to advances in the field. Gene-specific alterations are not the only determinants that can successfully direct the use of targeted therapy. Indeed, successful inhibition of BRAF or KRAS in metastatic CRCs driven by activating mutations in these genes requires combinations of drugs that inhibit the mutant protein while at the same time restraining adaptive resistance via CRC-specific EGFR-mediated feedback loops. The emerging paradigm is, therefore, that the intrinsic biology of CRC cells must be considered alongside the molecular profiles of individual tumours in order to successfully personalize treatment. In this Review, we outline how preclinical studies based on patient-derived models have informed the design of practice-changing clinical trials. The integration of these experiences into a common framework will reshape the future design of biology-informed clinical trials in this field.
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ISSN:1759-4774
1759-4782
1759-4782
DOI:10.1038/s41571-021-00495-z