Anticancer Therapeutic Strategies Targeting p53 Aggregation.

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• The tumor suppressor protein p53 is frequently mutated in over 50% of human cancers.
• Mutations often lead to oncogenic gain of function (GOF), promoting p53 aggregation via phase separation and transition.
• p53 aggregation contributes to chemoresistance, complicating cancer treatment.

Purpose of the Study:

• To review novel therapeutic strategies targeting p53 aggregates in cancer.
• To classify anticancer molecules that inhibit p53 aggregation.
• To explore the role of autophagy in degrading aggregated p53.

Main Methods:

• Literature review of studies on p53 aggregation and anticancer agents.
• Classification of anti-p53 aggregation molecules into four categories.
• Discussion of autophagy as a potential therapeutic pathway.

Main Results:

• Identified four categories of molecules with anti-p53 aggregation properties: thiol alkylating agents, designed peptides, chaperone-based inhibitors, and miscellaneous compounds.
• Highlighted the potential of autophagy for degrading aggregated p53.
• Reviewed strategies to disrupt p53 aggregates for cancer regression.

Conclusions:

• Targeting p53 aggregates represents a promising strategy for cancer therapy.
• Cancer can be viewed as a protein aggregation disease, amenable to anti-aggregation treatments.
• Further research into anti-p53 aggregation molecules and autophagy is warranted.