Small molecules targeting mutant p53: A promising approach for cancer treatment

Elizabeth A. Lopes, Sara Gomes, Lucília Saraiva, Maria M.M. Santos (Lead / Corresponding author)

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

More than half of all human tumors express mutant forms of p53, with the ovary, lung, pancreas, and colorectal cancers among the tumor types that display the highest prevalence of p53 mutations. In addition, the expression of mutant forms of p53 in tumors is associated with poor prognosis due to increased chemoresistance and invasiveness. Therefore, the pharmacological restoration of wild-type-like activity to mutant p53 arises as a promising therapeutic strategy against cancer. This review is focused on the most relevant mutant p53 small molecule reactivators described to date. Despite some of them have entered into clinical trials, none has reached the clinic, which emphasizes that new pharmacological alternatives, particularly with higher selectivity and lower adverse toxic side effects, are still required.

Original languageEnglish
Pages (from-to)7323-7336
Number of pages14
JournalCurrent Medicinal Chemistry
Volume26
Issue number41
DOIs
Publication statusPublished - 2019

Keywords

  • Cancer
  • Chemotherapy
  • Mutant p53
  • P53 tumor suppressor
  • Reactivators
  • Small molecules

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