Targeting p53 activation: Recent therapeutic advances in cancer and diabetic macular edema
Zhiyi Wang1, Shijie Zhang2, Loïca Mélita Irakoze2
1School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Rd., Shanghai, 201203, China.
Abstract:
p53, encoded by the TP53 gene, is a critical tumor suppressor, and its pharmacological activation has been clinically validated as an effective strategy for the treatment of human malignancies. In recent years, numerous novel approaches have emerged to activate both wild-type and mutant p53, including MDM2 degraders, p53 stabilizers, gene therapies targeting TP53, and inhibitors of the MDM2-p53 protein-protein interaction. Since 2020, drug discovery efforts in these areas have advanced rapidly, leading to several notable breakthroughs. This review provides a comprehensive overview of recently reported agents that enhance p53 function, with particular emphasis on those that have progressed to clinical trials or are capable of restoring p53 activity in cancers harboring TP53 mutations. We aim to offer an up-to-date snapshot of the evolving landscape of p53-targeted therapies and to serve as a reference for future drug discovery endeavors in this important field.
Insights
Activating p53, a key tumor suppressor, shows promise for cancer treatment. Recent drug discovery efforts focus on novel therapies targeting both wild-type and mutant p53 for enhanced cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- p53 is a crucial tumor suppressor protein encoded by the TP53 gene.
- Pharmacological activation of p53 is a validated strategy for treating human cancers.
- Dysregulation of p53 is common in many malignancies, driving tumor development.
Purpose of the Study:
- To provide a comprehensive review of recent agents designed to enhance p53 function.
- To highlight therapies targeting both wild-type and mutant p53.
- To focus on agents that have advanced to clinical trials or restore p53 activity in TP53-mutated cancers.
Main Methods:
- Literature review of recent scientific publications and clinical trial data.
- Focus on novel therapeutic strategies including MDM2 degraders, p53 stabilizers, gene therapies, and MDM2-p53 interaction inhibitors.
- Analysis of agents capable of restoring p53 activity in specific cancer contexts.
Main Results:
- Significant advancements in drug discovery for p53-targeted therapies since 2020.
- Identification of several novel agents progressing towards or currently in clinical trials.
- Emergence of strategies effective against both wild-type and mutant p53, including in TP53-mutated cancers.
Conclusions:
- The field of p53-targeted cancer therapy is rapidly evolving with promising new agents.
- Recent breakthroughs offer new hope for treating cancers with TP53 mutations.
- This review serves as a valuable reference for ongoing and future drug discovery in p53-based cancer therapeutics.
More Related Videos
06:48Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium
Published on: August 7, 2015
11:13Adenoviral Gene Therapy for Diabetic Keratopathy: Effects on Wound Healing and Stem Cell Marker Expression in Human Organ-cultured Corneas and Limbal Epithelial Cells
Published on: April 7, 2016
Related Concept Videos
01:22iPS Cell Differentiation
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...