How to manage KRAS G12C-mutated advanced non-small-cell lung cancer

Biagio Ricciuti; Alessia Mira; Elisa Andrini; Pietro Scaparone; Sandra Vietti Michelina; Federica Pecci; Luca Cantini; Andrea De Giglio; Giuseppe Lamberti; Chiara Ambrogio; Giulio Metro

doi:10.7573/dic.2022-7-4

How to manage KRAS G12C-mutated advanced non-small-cell lung cancer

Biagio Ricciuti^*
, Alessia Mira
, Elisa Andrini
, Pietro Scaparone
, Sandra Vietti Michelina
, Federica Pecci
, Luca Cantini
, Andrea De Giglio
, Giuseppe Lamberti
, Chiara Ambrogio
, Giulio Metro

^*Corresponding author for this work

Pulmonary Medicine

Hebrew SeniorLife
University of Turin
S. Orsola-Malpighi Hospital
University Hospital of Perugia

Research output: Contribution to journal › Review article › Academic › peer-review

11 Citations (Scopus)

57 Downloads (Pure)

Abstract

Constitutive KRAS signalling drives tumorigenesis across several cancer types. In non-small-cell lung cancer (NSCLC) activating KRAS mutations occur in ~30% of cases, and the glycine to cysteine substitution at codon 12 (G12C) is the most common KRAS alteration. Although KRAS mutations have been considered undruggable for over 40 years, the recent discovery of allelic-specific KRAS inhibitors has paved the way to personalized cancer medicine for patients with tumours harbouring these mutations. Here, we review the current treatment landscape for patients with advanced NSCLCs harbouring a KRAS G12C mutation, including PD-(L) 1-based therapies and direct KRAS inhibitors as well as sequential treatment options. We also explore the possible mechanisms of resistance to KRAS inhibition and strategies to overcome resistance in patients with KRAS G12C-mutant NSCLC.

Original language	English
Journal	Drugs in Context
Volume	11
DOIs	https://doi.org/10.7573/dic.2022-7-4
Publication status	Published - 16 Nov 2022

Bibliographical note

Acknowledgements: Molecular graphics and analyses performed with UCSF Chimera, developed by the Resource for Biocomputing,
Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311).

Publisher Copyright:
Copyright © 2022 Ricciuti B, Mira A, Andrini E, Scaparone P, Vietti Michelina S, Pecci F, Cantini L, De Giglio A, Lamberti G, Ambrogio C, Metro G.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.7573/dic.2022-7-4Licence: CC BY-NC-ND

dic.2022-7-4Final published version, 979 KBLicence: CC BY-NC-ND

Cite this

@article{fd4f457419d14735aa0f1f7fd7599848,

title = "How to manage KRAS G12C-mutated advanced non-small-cell lung cancer",

abstract = "Constitutive KRAS signalling drives tumorigenesis across several cancer types. In non-small-cell lung cancer (NSCLC) activating KRAS mutations occur in \textasciitilde{}30\% of cases, and the glycine to cysteine substitution at codon 12 (G12C) is the most common KRAS alteration. Although KRAS mutations have been considered undruggable for over 40 years, the recent discovery of allelic-specific KRAS inhibitors has paved the way to personalized cancer medicine for patients with tumours harbouring these mutations. Here, we review the current treatment landscape for patients with advanced NSCLCs harbouring a KRAS G12C mutation, including PD-(L) 1-based therapies and direct KRAS inhibitors as well as sequential treatment options. We also explore the possible mechanisms of resistance to KRAS inhibition and strategies to overcome resistance in patients with KRAS G12C-mutant NSCLC.",

author = "Biagio Ricciuti and Alessia Mira and Elisa Andrini and Pietro Scaparone and Michelina, \{Sandra Vietti\} and Federica Pecci and Luca Cantini and \{De Giglio\}, Andrea and Giuseppe Lamberti and Chiara Ambrogio and Giulio Metro",

note = "Acknowledgements: Molecular graphics and analyses performed with UCSF Chimera, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311). Publisher Copyright: Copyright {\textcopyright} 2022 Ricciuti B, Mira A, Andrini E, Scaparone P, Vietti Michelina S, Pecci F, Cantini L, De Giglio A, Lamberti G, Ambrogio C, Metro G.",

year = "2022",

month = nov,

day = "16",

doi = "10.7573/dic.2022-7-4",

language = "English",

volume = "11",

journal = "Drugs in Context",

issn = "1745-1981",

publisher = "Bioexcel Publishing LTD",

}

TY - JOUR

T1 - How to manage KRAS G12C-mutated advanced non-small-cell lung cancer

AU - Ricciuti, Biagio

AU - Mira, Alessia

AU - Andrini, Elisa

AU - Scaparone, Pietro

AU - Michelina, Sandra Vietti

AU - Pecci, Federica

AU - Cantini, Luca

AU - De Giglio, Andrea

AU - Lamberti, Giuseppe

AU - Ambrogio, Chiara

AU - Metro, Giulio

N1 - Acknowledgements: Molecular graphics and analyses performed with UCSF Chimera, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311). Publisher Copyright: Copyright © 2022 Ricciuti B, Mira A, Andrini E, Scaparone P, Vietti Michelina S, Pecci F, Cantini L, De Giglio A, Lamberti G, Ambrogio C, Metro G.

PY - 2022/11/16

Y1 - 2022/11/16

N2 - Constitutive KRAS signalling drives tumorigenesis across several cancer types. In non-small-cell lung cancer (NSCLC) activating KRAS mutations occur in ~30% of cases, and the glycine to cysteine substitution at codon 12 (G12C) is the most common KRAS alteration. Although KRAS mutations have been considered undruggable for over 40 years, the recent discovery of allelic-specific KRAS inhibitors has paved the way to personalized cancer medicine for patients with tumours harbouring these mutations. Here, we review the current treatment landscape for patients with advanced NSCLCs harbouring a KRAS G12C mutation, including PD-(L) 1-based therapies and direct KRAS inhibitors as well as sequential treatment options. We also explore the possible mechanisms of resistance to KRAS inhibition and strategies to overcome resistance in patients with KRAS G12C-mutant NSCLC.

AB - Constitutive KRAS signalling drives tumorigenesis across several cancer types. In non-small-cell lung cancer (NSCLC) activating KRAS mutations occur in ~30% of cases, and the glycine to cysteine substitution at codon 12 (G12C) is the most common KRAS alteration. Although KRAS mutations have been considered undruggable for over 40 years, the recent discovery of allelic-specific KRAS inhibitors has paved the way to personalized cancer medicine for patients with tumours harbouring these mutations. Here, we review the current treatment landscape for patients with advanced NSCLCs harbouring a KRAS G12C mutation, including PD-(L) 1-based therapies and direct KRAS inhibitors as well as sequential treatment options. We also explore the possible mechanisms of resistance to KRAS inhibition and strategies to overcome resistance in patients with KRAS G12C-mutant NSCLC.

UR - https://www.scopus.com/pages/publications/85148077308

U2 - 10.7573/dic.2022-7-4

DO - 10.7573/dic.2022-7-4

M3 - Review article

C2 - 36452878

AN - SCOPUS:85148077308

SN - 1745-1981

VL - 11

JO - Drugs in Context

JF - Drugs in Context

ER -

How to manage KRAS G12C-mutated advanced non-small-cell lung cancer

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this