Drug-Resistant Cancer Destroyed by New Molecule

Researchers at the Harvard University Medical School (HMS) and the Dana–Farber Cancer Institute (DFCI) announce the discovery of a molecule that is capable of inducing programmed cell death (apoptosis) in drug-resistant cancer cells.

The compound is called P5091, and it has proven to be very effective against drug-resistant myeloma cells growing in the laboratory. What remains to be proven beyond a doubt is whether or not it can do the same inside living tissue as well.

According to the group, the tumor cells they used for these experiments were resistant to Velcade, a drug commonly used to address cancer in numerous patients. P5091 appeared not to take notice of the cancerous cells' resistance to other therapeutic agents.

Details of exactly how the small molecule produces such a big effect appear in a paper published in the latest online issue of the esteemed peer-reviewed journal Cancer Cell, which is edited by Cell Press.

During the experiments, the team also noticed that the effectiveness of P5091 could be further increased by combining it with other drugs that are common choices for oncologists in treating cancer.

The molecule acts on a mechanism present in all cells, which is responsible for breaking down excess proteins inside the cell that are no longer needed. This process plays an important role in apoptosis, which occurs when the cell reaches the end of its natural life span.

When cancer affects cells, it shuts down the processes leading to apoptosis, which means that the infected cells can grow, multiply and mutate indefinitely. P5091 acts by restoring apoptosis, a process that destroys the cell from within.

“Velcade was one of the first in a class of drugs known as proteasome inhibitors to be approved by the U.S. Food and Drug Administration for multiple myeloma treatment,” Dharminder Chauhan explains.

The expert holds an appointment as the principal associate in medicine at HMS, and is also based at the DFCI. He was the lead author of the new Cancer Cell research paper. DFCI colleague and instructor in medicine, Ze Tian, was also part of the team.

“While Velcade is successful in many patients with multiple myeloma, it often loses its effectiveness over time, which prompted us to seek other drug targets,” Chauhan concludes.