p73: From the p53 shadow to a major pharmacological target in anticancer therapy

Area of Science:

• Molecular Biology
• Genetics
• Cancer Research

Background:

• p73 is a transcription factor belonging to the p53 family, with roles in neuronal development and tumor suppression.
• Unlike p53, the TP73 gene is rarely mutated in tumors, making p73 an attractive therapeutic target.
• TP73 generates distinct isoforms, TAp73 (with transactivation domain) and ΔNp73 (without), which have opposing functions in cancer.

Purpose of the Study:

• To provide an updated overview of p73 structure, biological functions, and pharmacological regulation.
• To highlight the relevance of p73 isoforms in carcinogenesis and their potential as anticancer drug targets.
• To critically discuss pharmacological approaches for enhancing p73 tumor suppressive activities and improving patient survival.

Main Methods:

• Literature review of p73 structure, function, and isoforms.
• Analysis of p73's role in various cancers and its therapeutic potential.
• Discussion of pharmacological strategies targeting p73.

Main Results:

• p73 exhibits unique functions beyond p53-like tumor suppression, including in neuronal development.
• ΔNp73 isoforms possess oncogenic properties by inhibiting p53 and TAp73 functions.
• Pharmacological modulation of p73 isoforms shows potential for cancer therapy.

Conclusions:

• p73 isoforms present a complex regulatory network with significant implications in cancer.
• Targeting p73, particularly in cancers with defective p53, represents a promising therapeutic avenue.
• Further research into pharmacological approaches is warranted to leverage p73's tumor-suppressive potential for improved cancer patient outcomes.