Small Molecules Targeting Programmed Cell Death in Breast Cancer Cells

Int J Mol Sci. 2021 Sep 8;22(18):9722. doi: 10.3390/ijms22189722.

Abstract

Targeted chemotherapy has become the forefront for cancer treatment in recent years. The selective and specific features allow more effective treatment with reduced side effects. Most targeted therapies, which include small molecules, act on specific molecular targets that are altered in tumour cells, mainly in cancers such as breast, lung, colorectal, lymphoma and leukaemia. With the recent exponential progress in drug development, programmed cell death, which includes apoptosis and autophagy, has become a promising therapeutic target. The research in identifying effective small molecules that target compensatory mechanisms in tumour cells alleviates the emergence of drug resistance. Due to the heterogenous nature of breast cancer, various attempts were made to overcome chemoresistance. Amongst breast cancers, triple negative breast cancer (TNBC) is of particular interest due to its heterogeneous nature in response to chemotherapy. TNBC represents approximately 15% of all breast tumours, however, and still has a poor prognosis. Unlike other breast tumours, signature targets lack for TNBCs, causing high morbidity and mortality. This review highlights several small molecules with promising preclinical data that target autophagy and apoptosis to induce cell death in TNBC cells.

Keywords: apoptosis; autophagy; breast cancer; programmed cell death; small molecule.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Autophagy / drug effects
  • Autophagy / genetics
  • Biological Products / chemistry
  • Biological Products / pharmacology
  • Biomarkers, Tumor*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / etiology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Drug Discovery* / methods
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects
  • Structure-Activity Relationship
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics

Substances

  • Antineoplastic Agents
  • Biological Products
  • Biomarkers, Tumor