Targeting pyruvate kinase muscle isoform 2 (PKM2) in cancer: What do we know so far?

Life Sci. 2021 Sep 1:280:119694. doi: 10.1016/j.lfs.2021.119694. Epub 2021 Jun 6.

Abstract

Cancer is a leading cause of death globally. Cancer cell transformation is the result of intricate crosstalk between intracellular components and proteins. A characteristic feature of cancer cells is the ability to reprogram their metabolic pathways to ensure their infinite proliferative potential. Pyruvate kinase muscle isoform 2 (PKM2) is a glycolytic enzyme that plays crucial roles in cancer, apart from carrying out its metabolic roles. PKM2 is involved in all the major events associated with cancer growth. Modulation of PKM2 activity (dimer inhibition or tetramer activation) has been successful in controlling cancer. However, recent studies provide contrary evidences regarding the oncogenic functions of PKM2. Moreover, several studies have highlighted the cancerous roles of PKM1 isoform in certain contexts. The present review aims at providing the current updates regarding PKM2 targeting in cancer. Further, the review discusses the contradictory results that suggest that both the isoforms of PKM can lead to cancer growth. In conclusion, the review emphasizes revisiting the approaches to target cancer metabolism through PKM to find novel and effective targets for anticancer therapy.

Keywords: Cancer; Cancer metabolism; PKM1; PKM2; Pyruvate kinase.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Carcinogenesis / drug effects
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Carrier Proteins / agonists
  • Carrier Proteins / analysis
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / metabolism*
  • Drug Discovery
  • Enzyme Activation / drug effects
  • Enzyme Activators / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Membrane Proteins / agonists
  • Membrane Proteins / analysis
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / agonists
  • Thyroid Hormones / analysis
  • Thyroid Hormones / metabolism*

Substances

  • Antineoplastic Agents
  • Carrier Proteins
  • Enzyme Activators
  • Enzyme Inhibitors
  • Membrane Proteins
  • Thyroid Hormones