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Targeting KRAS in pancreatic cancer: new drugs on the horizon.

ABSTRACT: Kirsten Rat Sarcoma (KRAS) is a master oncogene involved in cellular proliferation and survival and is the most commonly mutated oncogene in all cancers. Activating KRAS mutations are present in over 90% of pancreatic ductal adenocarcinoma (PDAC) cases and are implicated in tumor initiation and progression. Although KRAS is a critical oncogene, and therefore an important therapeutic target, its therapeutic inhibition has been very challenging, and only recently specific mutant KRAS inhibitors have been discovered. In this review, we discuss the activation of KRAS signaling and the role of mutant KRAS in PDAC development. KRAS has long been considered undruggable, and many drug discovery efforts which focused on indirect targeting have been unsuccessful. We discuss the various efforts for therapeutic targeting of KRAS. Further, we explore the reasons behind these obstacles, novel successful approaches to target mutant KRAS including G12C mutation as well as the mechanisms of resistance.

SUBMITTER: Bannoura SF

PROVIDER: S-EPMC8556325 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Targeting KRAS in pancreatic cancer: new drugs on the horizon.

Bannoura Sahar F SF Uddin Md Hafiz MH Nagasaka Misako M Fazili Farzeen F Al-Hallak Mohammed Najeeb MN Philip Philip A PA El-Rayes Bassel B Azmi Asfar S AS

Cancer metastasis reviews 20210909 3

Kirsten Rat Sarcoma (KRAS) is a master oncogene involved in cellular proliferation and survival and is the most commonly mutated oncogene in all cancers. Activating KRAS mutations are present in over 90% of pancreatic ductal adenocarcinoma (PDAC) cases and are implicated in tumor initiation and progression. Although KRAS is a critical oncogene, and therefore an important therapeutic target, its therapeutic inhibition has been very challenging, and only recently specific mutant KRAS inhibitors ha ...[more]

PMID: 34499267

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Dataset Information

Targeting KRAS in pancreatic cancer: new drugs on the horizon.

Publications

Targeting KRAS in pancreatic cancer: new drugs on the horizon.

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