The Therapeutic Potential of the Restoration of the p53 Protein Family Members in the EGFR-Mutated Lung Cancer

Int J Mol Sci. 2022 Jun 29;23(13):7213. doi: 10.3390/ijms23137213.

Abstract

Despite the recent development of precision medicine and targeted therapies, lung cancer remains the top cause of cancer-related mortality worldwide. The patients diagnosed with metastatic disease have a five-year survival rate lower than 6%. In metastatic disease, EGFR is the most common driver of mutation, with the most common co-driver hitting TP53. EGFR-positive patients are offered the frontline treatment with tyrosine kinase inhibitors, yet the development of resistance and the lack of alternative therapies make this group of patients only fit for clinical trial participation. Since mutant p53 is the most common co-driver in the metastatic setting, therapies reactivating the p53 pathway might serve as a promising alternative therapeutic approach in patients who have developed a resistance to tyrosine kinase inhibitors. This review focuses on the molecular background of EGFR-mutated lung cancer and discusses novel therapeutic options converging on the reactivation of p53 tumor suppressor pathways.

Keywords: EGFR; TKI resistance; drug repurposing; lung cancer; molecular targeted therapies; p53; p73.

Publication types

  • Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Protein Kinase Inhibitors
  • Tumor Suppressor Protein p53
  • EGFR protein, human
  • ErbB Receptors