On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma

C.R. Lindsay; M.C. Garassino; E. Nadal; K. Öhrling; M. Scheffler; J. Mazières

doi:10.1016/j.lungcan.2021.07.005

On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma

C.R. Lindsay, M.C. Garassino, E. Nadal, K. Öhrling, M. Scheffler, J. Mazières

Division of Cancer Sciences (L5)

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

Abstract

Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer death. Approximately one-third of patients with NSCLC have a KRAS mutation. KRAS ^G12C, the most common mutation, is found in ~13% of patients. While KRAS was long considered ‘undruggable’, several novel direct KRAS ^G12C inhibitors have shown encouraging signs of efficacy in phase I/II trials and one of these (sotorasib) has recently been approved by the US Food and Drug Administration. This review examines the role of KRAS mutations in NSCLC and the challenges in targeting KRAS. Based on specific KRAS biology, it reports exciting progress, exploring the use of novel direct KRAS inhibitors as monotherapy or in combination with other targeted therapies, chemotherapy, and immunotherapy.

Original language	English
Pages (from-to)	152-165
Number of pages	14
Journal	Lung Cancer
Volume	160
Early online date	16 Jul 2021
DOIs	https://doi.org/10.1016/j.lungcan.2021.07.005
Publication status	Published - 1 Oct 2021

Keywords

G12C
Immunotherapy
Lung cancer
Oncogene
Targeted therapy

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

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

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10.1016/j.lungcan.2021.07.005

Cite this

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title = "On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma",

abstract = "Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer death. Approximately one-third of patients with NSCLC have a KRAS mutation. KRAS G12C, the most common mutation, is found in ~13% of patients. While KRAS was long considered {\textquoteleft}undruggable{\textquoteright}, several novel direct KRAS G12C inhibitors have shown encouraging signs of efficacy in phase I/II trials and one of these (sotorasib) has recently been approved by the US Food and Drug Administration. This review examines the role of KRAS mutations in NSCLC and the challenges in targeting KRAS. Based on specific KRAS biology, it reports exciting progress, exploring the use of novel direct KRAS inhibitors as monotherapy or in combination with other targeted therapies, chemotherapy, and immunotherapy. ",

keywords = "G12C, Immunotherapy, Lung cancer, Oncogene, Targeted therapy",

author = "C.R. Lindsay and M.C. Garassino and E. Nadal and K. {\"O}hrling and M. Scheffler and J. Mazi{\`e}res",

year = "2021",

month = oct,

day = "1",

doi = "10.1016/j.lungcan.2021.07.005",

language = "English",

volume = "160",

pages = "152--165",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma

AU - Lindsay, C.R.

AU - Garassino, M.C.

AU - Nadal, E.

AU - Öhrling, K.

AU - Scheffler, M.

AU - Mazières, J.

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer death. Approximately one-third of patients with NSCLC have a KRAS mutation. KRAS G12C, the most common mutation, is found in ~13% of patients. While KRAS was long considered ‘undruggable’, several novel direct KRAS G12C inhibitors have shown encouraging signs of efficacy in phase I/II trials and one of these (sotorasib) has recently been approved by the US Food and Drug Administration. This review examines the role of KRAS mutations in NSCLC and the challenges in targeting KRAS. Based on specific KRAS biology, it reports exciting progress, exploring the use of novel direct KRAS inhibitors as monotherapy or in combination with other targeted therapies, chemotherapy, and immunotherapy.

AB - Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer death. Approximately one-third of patients with NSCLC have a KRAS mutation. KRAS G12C, the most common mutation, is found in ~13% of patients. While KRAS was long considered ‘undruggable’, several novel direct KRAS G12C inhibitors have shown encouraging signs of efficacy in phase I/II trials and one of these (sotorasib) has recently been approved by the US Food and Drug Administration. This review examines the role of KRAS mutations in NSCLC and the challenges in targeting KRAS. Based on specific KRAS biology, it reports exciting progress, exploring the use of novel direct KRAS inhibitors as monotherapy or in combination with other targeted therapies, chemotherapy, and immunotherapy.

KW - G12C

KW - Immunotherapy

KW - Lung cancer

KW - Oncogene

KW - Targeted therapy

U2 - 10.1016/j.lungcan.2021.07.005

DO - 10.1016/j.lungcan.2021.07.005

M3 - Review article

SN - 0169-5002

VL - 160

SP - 152

EP - 165

JO - Lung Cancer

JF - Lung Cancer

ER -

On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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