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Neo-RAS Wild Type or RAS Conversion in Metastatic Colorectal Cancer: A Comprehensive Narrative Review
by
, , , and
Guido Pesola
1,†,
Samantha Epistolio
2,†,
Marco Cefalì
1,
Elena Trevisi
1,
Sara De Dosso
1,3,‡ and
Milo Frattini
2,*,‡
1
Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland
2
Laboratory of Genetics and Molecular Pathology, Istituto Cantonale di Patologia EOC, 6600 Locarno, Switzerland
3
Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work and share co-first authorship.
‡
These authors contributed equally to this work and share co-last authorship.
Cancers 2024, 16(23), 3923; https://doi.org/10.3390/cancers16233923
Submission received: 6 September 2024
/
Revised: 20 November 2024
/
Accepted: 20 November 2024
/
Published: 22 November 2024
(This article belongs to the Special Issue RAS Signaling Pathway in Cancer Therapy)
Simple Summary
Patients with RAS-mutant metastatic colorectal cancer are typically treated with chemotherapy, with or without bevacizumab, as the first-line therapy. Over time, tumors in some patients may undergo plasma clearance of RAS, transitioning from being RAS-mutant to RAS-wild type, a phenomenon known as “RAS conversion” or “neo-RAS wild type”. The current review focuses on this phenomenon’s incidence, evaluation methodologies, and therapeutic implications, with a focus on the role that bevacizumab plays in it and its prospects.
Abstract
The management of metastatic colorectal cancer in patients harboring RAS mutations primarily involves chemotherapy, often combined with bevacizumab, as a standard first-line treatment. However, emerging evidence suggests that tumors in a subset of these patients may experience a conversion from RAS-mutant status to RAS wild type (wt) during or after chemotherapy, a process referred to as “RAS conversion” or “neo-RAS wt”. Understanding the mechanisms driving the neo-RAS wt phenomenon is crucial for its application in personalized medicine. Hypotheses suggest that selective pressure from chemotherapy may lead to a decrease in the number of mutant RAS clones or an outgrowth of pre-existing RAS wt clones. Further research is needed to validate these mechanisms and understand the impact of the neo-RAS wt phenomenon on long-term outcomes, such as overall survival and progression-free survival. This review provides a comprehensive overview of the current understanding of the neo-RAS wt phenomenon, including its incidence, potential mechanisms, and clinical implications.
Keywords:
RAS conversion; neo-RAS wild type; liquid biopsy; colorectal cancer; bevacizumab
