A collaborative breast cancer research project has received funding through the Fiscal Year 2025 Breast Cancer Research Program Breakthrough Award, administered by the Congressionally Directed Medical Research Programs (CDMRP).  

The award recognises the scientific merit, innovation, and collaborative strength of the research teams led by Dr Katerina Gurova at Roswell Park Comprehensive Cancer Center and Dr Karsten Eastman, CEO at Sethera Therapeutics. 

The project focuses on one of the most common and difficult problems in cancer biology: mutations in p53. In healthy cells, p53 helps prevent damaged cells from continuing to grow. In many cancers, including aggressive breast cancers, p53 becomes mutated and loses this protective function. These mutant forms of p53 can adopt abnormal conformations that allow cancer cells to survive, divide, and resist treatment. 

Sethera will use its polymacrocyclic peptide (pMCP) platform to discover constrained peptide molecules that bind mutant p53 and stabilise conformations associated with restored tumour-suppressive activity. Rather than simply blocking a cancer target, the goal is to identify molecules capable of modulating mutant p53 structure and function in ways that are difficult to achieve with conventional modalities. This approach could support a new therapeutic strategy for breast cancers driven by p53 mutations, including forms of the disease that currently have limited targeted treatment options. 

“This programme represents an important external validation of both our platform and our strategy of applying architecture-diverse peptides to targets that have remained beyond the practical reach of many established drug classes,” said Eastman. “Mutant p53 is an especially compelling test because its biological activity is closely linked to its three-dimensional structure. By working with Dr Gurova and the Roswell Park team, we can evaluate not only whether our molecules bind mutant p53, but whether they can produce meaningful functional rescue in disease-relevant systems.”