Finding the sweet spot: Targeting RAS in tumors while sparing normal tissue

Naiara Perurena; Karen Cichowski

doi:10.1016/j.ccell.2024.05.020

Finding the sweet spot: Targeting RAS in tumors while sparing normal tissue

Cancer Cell. 2024 Jun 10;42(6):943-945. doi: 10.1016/j.ccell.2024.05.020.

Authors

Naiara Perurena¹, Karen Cichowski²

Affiliations

¹ Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
² Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kcichowski@bwh.harvard.edu.

PMID: 38861932
DOI: 10.1016/j.ccell.2024.05.020

Abstract

The development of mutant-selective KRAS inhibitors represents a major therapeutic advance; however, patients can develop resistance through feedback mechanisms and genetic alterations in the RAS pathway. Three publications in Nature and Cancer Discovery describe a promising RAS(ON) multi-selective inhibitor that simultaneously targets oncogenic RAS and multiple potential resistance mechanisms while sparing normal tissue.

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Drug Resistance, Neoplasm / genetics
Humans
Molecular Targeted Therapy / methods
Mutation
Neoplasms* / drug therapy
Neoplasms* / genetics
Neoplasms* / metabolism
Neoplasms* / pathology
Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors
Proto-Oncogene Proteins p21(ras) / genetics
Proto-Oncogene Proteins p21(ras) / metabolism
Signal Transduction / drug effects
ras Proteins / genetics
ras Proteins / metabolism

Substances

Proto-Oncogene Proteins p21(ras)
ras Proteins
Antineoplastic Agents
KRAS protein, human