Rerouting the drug response: overcoming metabolic adaptation in KRAS-mutant cancers

Deborah Y. Moss; Christopher McCann; Emma M. Kerr

doi:10.1126/scisignal.abj3490

Rerouting the drug response: overcoming metabolic adaptation in KRAS-mutant cancers

Deborah Y. Moss, Christopher McCann, Emma M. Kerr^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Mutations in guanosine triphosphatase KRAS are common in lung, colorectal, and pancreatic cancers. The constitutive activity of mutant KRAS and its downstream signaling pathways induces metabolic rewiring in tumor cells that can promote resistance to existing therapeutics. In this review, we discuss the metabolic pathways that are altered in response to treatment and those that can, in turn, alter treatment efficacy, as well as the role of metabolism in the tumor microenvironment (TME) in dictating the therapeutic response in KRAS-driven cancers. We highlight metabolic targets that may provide clinical opportunities to overcome therapeutic resistance and improve survival in patients with these aggressive cancers.

Original language	English
Article number	eabj3490
Journal	Science Signaling
Volume	15
Issue number	756
DOIs	https://doi.org/10.1126/scisignal.abj3490
Publication status	Published - 18 Oct 2022

Keywords

Tumor Microenvironment - genetics
Proto-Oncogene Proteins p21(ras) - genetics - metabolism
Guanosine
Mutation
Cell Line, Tumor
Pancreatic Neoplasms - drug therapy - genetics - metabolism
Humans
Signal Transduction

UN SDGs

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

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10.1126/scisignal.abj3490Licence: Unspecified

Identification of mitochondrial metabolism as a driver of chemotherapy resistance in colorectal cancer
Moss, D. (Author), Mills, I. (Supervisor), Wilson, M. (Supervisor) & Kerr, E. (Supervisor), Jul 2023
Student thesis: Doctoral Thesis › Doctor of Philosophy

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title = "Rerouting the drug response: overcoming metabolic adaptation in KRAS-mutant cancers",

abstract = "Mutations in guanosine triphosphatase KRAS are common in lung, colorectal, and pancreatic cancers. The constitutive activity of mutant KRAS and its downstream signaling pathways induces metabolic rewiring in tumor cells that can promote resistance to existing therapeutics. In this review, we discuss the metabolic pathways that are altered in response to treatment and those that can, in turn, alter treatment efficacy, as well as the role of metabolism in the tumor microenvironment (TME) in dictating the therapeutic response in KRAS-driven cancers. We highlight metabolic targets that may provide clinical opportunities to overcome therapeutic resistance and improve survival in patients with these aggressive cancers.",

keywords = "Tumor Microenvironment - genetics, Proto-Oncogene Proteins p21(ras) - genetics - metabolism, Guanosine, Mutation, Cell Line, Tumor, Pancreatic Neoplasms - drug therapy - genetics - metabolism, Humans, Signal Transduction",

author = "Moss, {Deborah Y.} and Christopher McCann and Kerr, {Emma M.}",

year = "2022",

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doi = "10.1126/scisignal.abj3490",

language = "English",

volume = "15",

journal = "Science Signaling",

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T1 - Rerouting the drug response: overcoming metabolic adaptation in KRAS-mutant cancers

AU - Moss, Deborah Y.

AU - McCann, Christopher

AU - Kerr, Emma M.

PY - 2022/10/18

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N2 - Mutations in guanosine triphosphatase KRAS are common in lung, colorectal, and pancreatic cancers. The constitutive activity of mutant KRAS and its downstream signaling pathways induces metabolic rewiring in tumor cells that can promote resistance to existing therapeutics. In this review, we discuss the metabolic pathways that are altered in response to treatment and those that can, in turn, alter treatment efficacy, as well as the role of metabolism in the tumor microenvironment (TME) in dictating the therapeutic response in KRAS-driven cancers. We highlight metabolic targets that may provide clinical opportunities to overcome therapeutic resistance and improve survival in patients with these aggressive cancers.

AB - Mutations in guanosine triphosphatase KRAS are common in lung, colorectal, and pancreatic cancers. The constitutive activity of mutant KRAS and its downstream signaling pathways induces metabolic rewiring in tumor cells that can promote resistance to existing therapeutics. In this review, we discuss the metabolic pathways that are altered in response to treatment and those that can, in turn, alter treatment efficacy, as well as the role of metabolism in the tumor microenvironment (TME) in dictating the therapeutic response in KRAS-driven cancers. We highlight metabolic targets that may provide clinical opportunities to overcome therapeutic resistance and improve survival in patients with these aggressive cancers.

KW - Tumor Microenvironment - genetics

KW - Proto-Oncogene Proteins p21(ras) - genetics - metabolism

KW - Guanosine

KW - Mutation

KW - Cell Line, Tumor

KW - Pancreatic Neoplasms - drug therapy - genetics - metabolism

KW - Humans

KW - Signal Transduction

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DO - 10.1126/scisignal.abj3490

M3 - Article

C2 - 36256706

SN - 1945-0877

VL - 15

JO - Science Signaling

JF - Science Signaling

IS - 756

M1 - eabj3490

ER -

Rerouting the drug response: overcoming metabolic adaptation in KRAS-mutant cancers

Abstract

Keywords

UN SDGs

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Student theses

Identification of mitochondrial metabolism as a driver of chemotherapy resistance in colorectal cancer

Cite this