Although some patients can be treated with surgery and chemotherapy, eventually most metastatic ovarian cancers become resistant to treatment. New options are needed for patients with advanced ovarian cancer.
Researchers are studying a protein fragment, or peptide, that has the potential to stimulate healthy cells in the tumor microenvironment surrounding cancer cells to block the cancer’s growth. So far, the treatment has been successful in causing tumor regression in animal models, according to the study results published in Science Translational Medicine.
The researchers used a protein called prosaposin to stimulate monocytes, which are immune cells that the bone marrow sends to metastatic sites, which in turn produce a protein called thrombospondin-1. In animal models, thrombospondin-1 inhibits the formation of new blood vessels to feed tumor cells and stimulates immune cells to kill cancer cells.
For the current study, the researchers created a cyclic version of prosaposin that can be used as a drug to trigger thrombospondin-1. They tested it in mice that had tumors formed by transplanted human ovarian cancer cells that expressed a receptor protein called CD36, which interacts with thrombospondin-1. The drug stopped the tumors’ progression and also shrunk the tumors so much that they were undetectable.
To determine how broadly this could affect treatment of metastatic ovarian cancer, the researches analyzed samples from 134 patients with the disease to look for CD36. Not only did 97% of the tumors express CD36, but the levels were higher in metastatic tumors than primary tumors.
In addition, the researchers identified another receptor called CD47 that triggers tumor-initiating cells to mature and complete cancer cell death. Thrombospondin-1 also mediates this process.
The study gives hope to practitioners looking for ways to prevent drug resistance, because the researchers noted that tumors may be less likely to develop resistance to drugs that target their microenvironments instead of the tumors themselves. However, they cautioned that additional studies are needed to develop a therapeutic agent for use in humans.