Approximately 80% of ovarian cancers are classified as a high-grade serous subtype, an aggressive form that usually isn’t diagnosed until advanced stages. Because of this, long-term survival rates are usually low. However, researchers in a new study have found a new treatment approach that may offer promise for the future of this particular form of ovarian cancer. The study findings were published in Cancer Cell.
Researchers know that nearly all high-grade serous ovarian cancers express mutant versions of the p53 protein. Healthy versions of this tumor suppressor protein are critical to prevent tumor formation; when mutated, p53 can become inactivated and allow tumors to grow.
The current study’s researchers looked for a way to reactivate mutant p53’s tumor-suppressor functions. They looked specifically at cases where mutant p53 clumps together into amyloid aggregates and found that some mutated forms have sticky spots that cause them to attach to each other. They designed a peptide called ReACp53 that can enter cells and block this aggregation.
In cell-based models, ReACp53 treatment led to extensive cancer cell death in cells that expressed mutant p53. It had no effect in cancers with normal p53 or those that did not express the protein.
In animal models of high-grade serous ovarian cancer, ReACp53 treatment caused both primary and metastatic tumors to shrink as much as 90% with no evidence of side effects. In mice that received a control treatment, the tumors grew to more than twice their size.
Although the findings are impressive, the data do not rule out other factors that could be responsible, so additional studies are needed. The researchers are also investigating ReACp53’s effect on other tumor types in which p53 is frequently mutated.