The first patient in a new Phase I clinical trial for mesothelioma has recently begun treatment. The trial is evaluating a combination of two novel drugs designed to attack mesothelioma stem cells, VS-6063 and VS-5584. Both drugs were developed by Verastem, Inc., a pharmaceutical company that has invested a lot of effort in treating mesothelioma.
VS-6063, also known as defactinib, and has already been the center of two mesothelioma clinical trials since 2013. One of these clinical trials is already in Phase II, meaning defactinib has shown little side effects and potential to effectively treat mesothelioma.
The new trial is the first time VS-5584 has been used to treat mesothelioma.
“We have dosed the first patient in our first-in-human combination study of VS-5584 and VS-6063 in mesothelioma and we look forward to providing updates as the trial progresses,” said President and Chief Executive Officer of Verastem, Inc. Robert Forrester in a recent press release.
Why Stem Cells?
Broad treatments for mesothelioma, such as chemotherapy, can kill the majority of mesothelioma cells and reduce the size of tumors. However, these treatments often leave traces of the cancer behind in which mesothelioma stem cells are prevalent.
Mesothelioma stem cells make up the minority of cells in a tumor. However, after a patient has been treated with standard chemotherapy, the remaining cancer stem cells are believed to build up a resistance to the chemotherapy drugs. This is why using the same chemotherapy drug for a relapsed patient who has already received the drug previously isn’t as effective the second time around.
Doctors have tried to overcome this obstacle by prescribing different chemotherapy drugs in relapsed patients, but only to minimal success.
Lingering mesothelioma stem cells are also the reason the cancer can grow back even after a patient shows no signs of mesothelioma.
Targeting the mesothelioma stem cells may be a way to reduce chemotherapy resistance in patients whose cancer has come back. However, targeting the mesothelioma stem cells could also prevent patients from relapsing at all or at least for a much longer time.
How Do These Drugs Work?
Defactinib and VS-5584 both use the same premise to fight mesothelioma, blocking signaling pathways that cancer stem cells use to spread and form new tumors.
Defactinib is a focal adhesion kinase (FAK) signaling pathway inhibitor. FAK is the protein that signals mesothelioma stem cells to reproduce new mesothelioma cells. The protein also helps cancer cells metastasize throughout the body. VS-5584 works in the same way, but it inhibits a different pathway, the PI3K signaling pathway.
Two Drugs Are Better Than One
Treatment for mesothelioma has been historically more successful when patients are given more than one drug. The most famous example of this is the combination of chemotherapy drugs Alimta and cisplatin.
Most patients are given Alimta and cisplatin during their first rounds of treatment. Both drugs have separately proven to have an effect on destroying mesothelioma cells and extending survival times. But combining the drugs is even more effective.
Following this example, treating patients with defactinib and VS-5584 could potentially be more effective than using only defactinib. Each drug inhibits a separate signaling pathway, each of which have been shown to support the proliferation of mesothelioma stem cells and the growth of new tumors. By setting up roadblocks at each pathway, doctors hope it will be even harder for tumors to grow back.
Sources & Author