Targeting the Oncogenic p53 Mutants in Colorectal Cancer and Other Solid Tumors
Hui Li1,2,3, Jinglin Zhang1,2,3, Joanna Hung Man Tong1,3
1Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
International Journal of Molecular Sciences
|December 5, 2019
Summary
TP53 mutations are key in colorectal cancer (CRC) progression, promoting tumor growth and chemoresistance. Targeting these mutated p53 proteins offers promising therapeutic strategies for various solid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Colorectal cancer (CRC) is a prevalent solid tumor globally, marked by genetic heterogeneity.
- TP53 mutations are critical drivers in CRC, facilitating the adenoma-to-adenocarcinoma transition.
- TP53 mutations are linked to poorer prognosis and chemoresistance in CRC patients.
Purpose of the Study:
- To review the gain-of-function (GOF) roles of p53 mutants in CRC and other solid tumors.
- To discuss current therapeutic strategies targeting p53 mutants in malignancies.
Main Methods:
- Comprehensive literature review of studies on TP53 mutations in cancer.
- Analysis of functional roles and therapeutic interventions related to p53 mutants.
Main Results:
- TP53 mutations confer a gain of function (GOF) to p53 mutants.
- GOF of p53 mutants enhances cell proliferation, migration, and invasion via multiple mechanisms.
- TP53 mutations are associated with poor prognosis and chemoresistance in colorectal cancer.
Conclusions:
- Targeting oncogenic p53 mutants, restoring wild-type p53, or depleting mutants are potential therapeutic avenues.
- Understanding p53 mutant GOF is crucial for developing effective cancer therapies.
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