PURPOSE: To review mechanisms underlying mutant p53 (mutp53) gain of function (GOF) and mutp53-induced chemoresistance, and to investigate the role of mutp53 in response to clinical chemotherapy. METHODS: We searched the PubMed database for clinical studies from the past decade, including data evaluating the impact of mutp53 in clinical chemotherapy response. RESULTS: Interactions between mutp53 and transcriptional factors, proteins or DNA structures, as well as epigenetic regulation, contribute to mutp53 GOF. Major mechanisms of mutp53-induced chemoresistance include enhanced drug efflux and metabolism, promoting survival, inhibiting apoptosis, upregulating DNA repair, suppressing autophagy, elevating microenvironmental resistance and inducing a stem-like phenotype. Clinically, mutp53 predicted resistance to chemotherapy in diffuse large B-cell lymphoma, and esophageal and oropharyngeal cancers, but its impact on chronic lymphocytic leukemia was unclear. In bladder cancer, mutp53 did not predict resistance, whereas in some breast and ovarian cancers, it was associated with sensitivity to certain chemotherapeutic agents. CONCLUSION: mutp53 has an intricate role in the response to clinical chemotherapy and should not be interpreted in isolation. Furthermore, when predicting tumor response to chemotherapy based on the p53 status, the drugs used should also be taken into consideration. These concepts require further investigation.
PURPOSE: To review mechanisms underlying mutant p53 (mutp53) gain of function (GOF) and mutp53-induced chemoresistance, and to investigate the role of mutp53 in response to clinical chemotherapy. METHODS: We searched the PubMed database for clinical studies from the past decade, including data evaluating the impact of mutp53 in clinical chemotherapy response. RESULTS: Interactions between mutp53 and transcriptional factors, proteins or DNA structures, as well as epigenetic regulation, contribute to mutp53 GOF. Major mechanisms of mutp53-induced chemoresistance include enhanced drug efflux and metabolism, promoting survival, inhibiting apoptosis, upregulating DNA repair, suppressing autophagy, elevating microenvironmental resistance and inducing a stem-like phenotype. Clinically, mutp53 predicted resistance to chemotherapy in diffuse large B-cell lymphoma, and esophageal and oropharyngeal cancers, but its impact on chronic lymphocytic leukemia was unclear. In bladder cancer, mutp53 did not predict resistance, whereas in some breast and ovarian cancers, it was associated with sensitivity to certain chemotherapeutic agents. CONCLUSION: mutp53 has an intricate role in the response to clinical chemotherapy and should not be interpreted in isolation. Furthermore, when predicting tumor response to chemotherapy based on the p53 status, the drugs used should also be taken into consideration. These concepts require further investigation.
Authors: George Iancu; Dragos Serban; Cristinel Dumitru Badiu; Ciprian Tanasescu; Mihai Silviu Tudosie; Corneliu Tudor; Daniel Ovidiu Costea; Anca Zgura; Raluca Iancu; Danut Vasile Journal: Exp Ther Med Date: 2021-12-03 Impact factor: 2.447
Authors: Fiebo J C Ten Kate; Lucia Suzuki; Lambert C J Dorssers; Winand N M Dinjens; David T W Jones; Daan Nieboer; Michael Doukas; J Jan B Van Lanschot; Bas P L Wijnhoven; Leendert H J Looijenga; Katharina Biermann Journal: Oncotarget Date: 2017-10-24
Authors: Stephanie Antoun; David Atallah; Roula Tahtouh; Nada Alaaeddine; Malak Moubarak; Abir Khaddage; Eliane Nasr Ayoub; George Chahine; George Hilal Journal: Cancer Cell Int Date: 2018-01-30 Impact factor: 5.722