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Review
. 2021 Mar:146:74-83.
doi: 10.1016/j.ejca.2021.01.015. Epub 2021 Feb 12.

RAS as a positive predictive biomarker: focus on lung and colorectal cancer patients

Umberto Malapelle  1 , Francesco Passiglia  2 , Chiara Cremolini  3 , Maria Lucia Reale  2 , Francesco Pepe  1 , Pasquale Pisapia  1 , Antonio Avallone  4 , Diego Cortinovis  5 , Alfonso De Stefano  4 , Matteo Fassan  6 , Gabriella Fontanini  7 , Domenico Galetta  8 , Calogero Lauricella  9 , Angela Listì  2 , Fotios Loupakis  10 , Fabio Pagni  11 , Filippo Pietrantonio  12 , Sara Pilotto  13 , Luisella Righi  2 , Andrea Sartore Bianchi  14 , Hector Soto Parra  15 , Marcello Tiseo  16 , Michela Verzè  16 , Giancarlo Troncone  17 , Silvia Novello  2
Affiliations
Review

RAS as a positive predictive biomarker: focus on lung and colorectal cancer patients

Umberto Malapelle et al. Eur J Cancer. 2021 Mar.

Abstract

Rat sarcoma (RAS) oncogenes have intensively been investigated during the last decades. Taking into account all human tumours, Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene is the most frequently mutated (about 22%) among the three isoforms, followed by Neuroblastoma RAS Viral Oncogene Homolog (NRAS) (8%) and Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS) (3%). In the last years, careful attention has been paid on KRAS and NRAS gene mutations in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) patients because of their prognostic and predictive roles. In particular, a large body of literature data has been generated investigating clinical outcomes of targeted treatments in NSCLC and CRC KRAS- and NRAS-mutated patients. The latest evidences are here reviewed, providing also an overview of the real-world RAS mutation testing practice across different Italian laboratories. On this basis, we propose a knowledge-based system, www.rasatlas.com, to support the healthcare personnel in the management of patients featuring RAS gene mutations in the landscape of precision oncology.

Keywords: CRC; KRAS; NGS; NRAS; NSCLC.

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Conflict of interest statement

Conflict of interest statement Umberto Malapelle has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, ThermoFisher Scientifics, Diaceutics, GSK, Merck and AstraZeneca, unrelated to the current work. Francesco Passiglia has received personal fees (as consultant and/or speaker bureau) from MSD, AstraZeneca, Boehringer Ingelheim, BMS and Pfizer, unrelated to the current work. Alfonso De Stefano received personal fees (as consultant and/or speaker) from Amgen, Merck and Italfarmaco, unrelated to the current work. Fabio Pagni has received personal fees (as consultant and/or speaker bureau) from, MSD, GSK, Merck and AstraZeneca, unrelated to the current work. Filippo Pietrantionio has received honoraria from Amgen, Roche, Merck-Serono, Bayer, Servier, Lilly and Sanofi, and research grants from BMS, unrelated to the current work. Sara Pilotto has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, BMS, Roche, MSD and AstraZeneca, unrelated to the current work. Luisella Righi has received personal fees (as consultant and/or speaker bureau) from Astra Zeneca, Novartis, Amgen and Boehringer Ingelheim, unrelated to the current work. Marcello Tiseo received speakers' and consultants’ fee from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda and Pierre Fabre, and institutional research grants from Astra-Zeneca, Boehringer Ingelheim, unrelated to the current work. Giancarlo Troncone reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer and Bayer, unrelated to the current work. Silvia Novello reports personal fees (as speaker bureau or advisor) from Eli Lilly, MSD, Roche, BMS, Takeda, Pfizer, Astra Zeneca and Boehringer Ingelheim, unrelated to the current work. The other authors declare no potential conflicts of interest.