There’s more evidence that experimental mesothelioma drugs that inhibit focal adhesion kinase (FAK) may have the ability to dramatically improve the effectiveness of chemotherapy for thousands of mesothelioma patients.
Verastem, Inc., the developer of the FAK inhibitors VS-6063 and VS-4718, has just published a new paper on the mechanism by which these drugs work in the medical journal Science Translational Medicine. The research describes how FAK inhibitors make certain mesothelioma cells more susceptible to common chemotherapy drugs like Alimta (pemetrexed) and cisplatin.
About half of mesothelioma patients are missing a tumor suppressor called merlin, which can be both good and bad news. Unfortunately, cancers that demonstrate merlin loss tend to be particularly aggressive and mesothelioma is known for its aggressiveness. But Verastem’s research suggests that these cancers are also particularly sensitive to drugs like VS-6063 that are designed to inhibit FAK.
“These preclinical results provide the rationale for a clinical trial in malignant pleural mesothelioma patients using an FAK inhibitor as a single agent after first-line chemotherapy,” writes Verastem researcher Irina Shapiro, the paper’s lead author. FAK inhibitors may be a helpful addition to chemotherapy because they not only attack the tumor cells, but they also target merlin-negative cancer stem cells (CSCs) – the cells responsible for mesothelioma relapse after chemotherapy.
“With this design, the FAK inhibitor could potentially induce a more durable clinical response through reduction of CSCs along with a strong antitumor effect,” adds Dr. Shapiro. Verastem found that its FAK inhibitors worked to destroy merlin-negative mesothelioma cells in the lab and in live mice infected with human mesothelioma.
Unlike FAK-inhibitors which target cancer stem cells, standard chemotherapy drugs like Alimta and cisplatin actually end up creating more stem cells, even while they are shrinking mesothelioma tumors. Verastem’s head of research, Dr. Jonathan Pachter, said in the statement that treating merlin-negative mesothelioma patients with a stem cell-targeting FAK inhibitor like VS-6063 after chemotherapy might help the cancer-fighting effects last longer.
Sources: Shapiro, IM et al, “Merlin Deficiency Predicts FAK Inhibitor Sensitivity: A Synthetic Lethal Relationship”, May 21, 2014, Science Translational Medicine, Vol. 6, Issue 237
“Verastem Published Scientific Data on Targeting Mesothelioma Cancer Stem Cells in Science Translational Medicine”, May 27, 2014, Verastem news release