KRAS as potential target in colorectal cancer therapy

Shu Kee Eng, Teng Hern Tan Loh, Bey Hing Goh, Wai Leng Lee

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

6 Citations (Scopus)

Abstract

Colorectal cancer (CRC) is among the most commonly diagnosed cancers affecting both genders in the world. It is characterized by genetic instability, which drives tumor formation via the activation of oncogenes, such as KRAS and B-RAF. Approximately 40% of CRC patients harbor the mutated KRAS oncogene as the predominant form of RAS mutation which plays a key role in the early development of cancer adenoma. The constitutively mutated K-Ras protein is able to bypass signals from its upstream effector, epidermal growth factor receptor (EGFR), thus rendering the existing anti-EGFR treatments (cetuximab and panitumumab) ineffective. However, there is no direct anti-KRAS treatment showing clinical benefits despite several decades of comprehensive efforts. To date, many efforts have been done to target the aberrant KRAS signaling at different levels including (1) inhibit RAS membrane association and (2) inhibit downstream KRAS effectors. The present chapter highlights the existing approaches in the management of KRAS-driven cancers by targeting RAS, and also discusses the potential drug candidates on this horizon.

Original languageEnglish
Title of host publicationNatural Bio-active Compounds
Subtitle of host publicationVolume 1: Production and Applications
EditorsMohd Sayeed Akhtar, Mallappa Kumara Swamy, Uma Rani Sinniah
Place of PublicationSingapore
PublisherSpringer-Verlag London Ltd.
Chapter12
Pages389-424
Number of pages36
Volume1
ISBN (Electronic)9789811371547
ISBN (Print)9789811371530
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Cancer
  • EGFR effector
  • Oncogene
  • RAS biology
  • Tumor formation

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