Related Experiment Video
Updated: Feb 1, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Mutant p53 in cancer therapy-the barrier or the path
Xiang Zhou1, Qian Hao2, Hua Lu3
1Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, and Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China.
Abstract:
Since wild-type p53 is central for maintaining genomic stability and preventing oncogenesis, its coding gene TP53 is highly mutated in ~50% of human cancers, and its activity is almost abrogated in the rest of cancers. Approximately 80% of p53 mutations are single point mutations with several hotspot mutations. Besides loss of function and dominant-negative effect on the wild-type p53 activity, the hotspot p53 mutants also acquire new oncogenic functions, so-called 'gain-of-functions' (GOF). Because the GOF of mutant p53 is highly associated with late-stage malignance and drug resistance, these p53 mutants have become hot targets for developing novel cancer therapies. In this essay, we review some recent progresses in better understanding of the role of mutant p53 GOF in chemoresistance and the underlying mechanisms, and discuss the pros and cons of targeting mutant p53 for the development of anti-cancer therapies.
Insights
Mutant p53 gain-of-function (GOF) mutations drive cancer progression and drug resistance. Targeting these oncogenic p53 mutants offers promising therapeutic strategies for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The tumor suppressor gene TP53 is frequently mutated in human cancers.
- Mutations in TP53 can lead to loss of function, dominant-negative effects, and oncogenic gain-of-function (GOF) activities.
- GOF mutations in p53 are linked to advanced malignancy and therapeutic resistance.
Purpose of the Study:
- To review recent advancements in understanding the role of mutant p53 GOF in chemoresistance.
- To explore the molecular mechanisms underlying mutant p53 GOF-mediated chemoresistance.
- To discuss the potential of targeting mutant p53 GOF for novel anti-cancer therapies.
Main Methods:
- Literature review of recent research on mutant p53.
- Analysis of molecular mechanisms of p53 GOF in cancer.
- Discussion of therapeutic strategies targeting mutant p53.
Main Results:
- Mutant p53 GOF contributes significantly to chemoresistance in various cancers.
- Specific molecular pathways are implicated in mediating the GOF effects of mutant p53.
- Targeting mutant p53 presents both opportunities and challenges for cancer therapy development.
Conclusions:
- Mutant p53 GOF is a critical factor in cancer chemoresistance and progression.
- Understanding these mechanisms is key to developing effective therapies.
- Targeting mutant p53 holds promise but requires careful consideration of associated challenges.
Related Concept Videos
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:22Mean free path and Mean free time
01:21Path Between Thermodynamics States
01:10Interference: Path Lengths
Two special sources may be considered when they are in phase. This can be easily achieved by feeding the two sources from the same source. An example would be synchronizing the two speakers by feeding them with the same source, such as the sound waves produced by a tuning fork. This setup ensures that the two sources have the same frequency and are...
03:48Behavior of Gas Molecules: Molecular Diffusion, Mean Free Path, and Effusion