Breakthrough in cancer therapy: targeting mutant p53 with novel inhibitors shows promise

In a groundbreaking review published in Current Molecular Pharmacology, a team led by Dr. Jhi Biau Foo from Taylor’s University unveils the pivotal role of mutant p53 (mutp53) in driving cancer progression and therapy resistance. Mutations in the TP53 gene, the most common genetic alteration in human cancers, disrupt p53’s tumor-suppressing functions, leading to uncontrolled cell growth and metastasis. "Mutant p53 not only loses its protective role but also gains oncogenic properties, making it a prime target for therapy," explained Dr. Foo.

The review highlights promising inhibitors like NSC319726, STIMA-1, and APR-246, which reactivate mutp53 by restoring its wild-type conformation or inducing apoptosis. APR-246, the most advanced candidate, has shown efficacy in Phase III trials for myelodysplastic syndrome (MDS). "APR-246’s success in clinical trials underscores its potential to transform cancer treatment," said Dr. Foo. Other compounds, such as ReACp53 and COTI-2, are also progressing, targeting mutp53 aggregation and enhancing chemotherapy sensitivity.

Despite challenges—like mutp53’s conformational diversity and drug resistance—the study emphasizes the therapeutic promise of these inhibitors. "Combining mutp53-targeting drugs with existing therapies could overcome resistance and improve outcomes," added Dr. Foo. With ongoing trials and novel compounds in development, the future of mutp53-targeted cancer therapy looks bright.