TY - JOUR
T1 - Small molecules targeting mutant p53
T2 - A promising approach for cancer treatment
AU - Lopes, Elizabeth A.
AU - Gomes, Sara
AU - Saraiva, Lucília
AU - Santos, Maria M.M.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Cancer
KW - Chemotherapy
KW - Mutant p53
KW - P53 tumor suppressor
KW - Reactivators
KW - Small molecules
UR - http://www.scopus.com/inward/record.url?scp=85077765807&partnerID=8YFLogxK
U2 - 10.2174/0929867325666181116124308
DO - 10.2174/0929867325666181116124308
M3 - Review article
C2 - 30444195
AN - SCOPUS:85077765807
VL - 26
SP - 7323
EP - 7336
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
SN - 0929-8673
IS - 41
ER -