Precision oncology in metastatic colorectal cancer - from biology to medicine.

Animals Colorectal Neoplasms / pathology Evidence-Based Medicine / methods Humans Neoplasm Metastasis Precision Medicine / methods Translational Research, Biomedical / methods

Journal

Nature reviews. Clinical oncology
ISSN: 1759-4782
Titre abrégé: Nat Rev Clin Oncol
Pays: England
ID NLM: 101500077

Informations de publication

Date de publication:
08 2021
Historique:
accepted: 01 03 2021
pubmed: 18 4 2021
medline: 18 9 2021
entrez: 17 4 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41571-021-00495-z PMID: 33864051
pubmed: 33864051
doi: 10.1038/s41571-021-00495-z
pii: 10.1038/s41571-021-00495-z
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

506-525

Informations de copyright

© 2021. Springer Nature Limited.

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Auteurs

Federica Di Nicolantonio (F)

Department of Oncology, University of Torino, Candiolo, Italy. federica.dinicolantonio@unito.it.
Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy. federica.dinicolantonio@unito.it.
ORCID: 0000-0001-9618-2010

Pietro Paolo Vitiello (PP)

Department of Oncology, University of Torino, Candiolo, Italy.
Department of Precision Medicine, Medical Oncology Unit, University of Campania Luigi Vanvitelli, Naples, Italy.

Silvia Marsoni (S)

Istituto FIRC di Oncologia Molecolare, Milan, Italy.
Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
ORCID: 0000-0002-5361-7122

Salvatore Siena (S)

Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
ORCID: 0000-0002-2681-2846

Josep Tabernero (J)

Vall d'Hebron University Hospital and Institute of Oncology, IOB-Quiron, UVic-UCC, Barcelona, Spain.
ORCID: 0000-0002-2495-8139

Livio Trusolino (L)

Department of Oncology, University of Torino, Candiolo, Italy.
Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy.

Rene Bernards (R)

Division of Molecular Carcinogenesis, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands.
ORCID: 0000-0001-8677-3423

Alberto Bardelli (A)

Department of Oncology, University of Torino, Candiolo, Italy. alberto.bardelli@unito.it.
Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy. alberto.bardelli@unito.it.
ORCID: 0000-0003-1647-5070

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