An FDA-approved drug currently used for treating multiple sclerosis has been found to be effective for pancreatic cancer. Researchers from Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, in collaboration with Regional Cancer Centre in the city and NIMHANS, Bengaluru, found that the drug was also able to increase the efficacy of gemcitabine, the current standard drug for pancreatic cancer. The results of the study have been recently published in Theranostics.
The drug used to treat multiple sclerosis was found to act through a receptor called S1PR1 that is involved in lipid signalling and which regulates numerous cellular events such as cell growth, migration and vascular integrity.
“The precise role of the receptor in pancreatic cancer is still not clear and our study has brought out its importance. We found that the [multiple] sclerosis drug can bind to the receptor and alter the key cellular events and prevent the progression of pancreatic cancer,” explains Dr. K.B. Harikumar, from the Cancer Research Program at RGCB and corresponding author of the paper. The sclerosis drug was also found to be a potent inhibitor of NF-kappaB, a transcription factor that helps in tumour progression.
The effectiveness of the multiple sclerosis drug when used together with the current pancreatic cancer drug was checked in mice models. The combination drug treatment was able to control various signalling molecules, thereby decreasing cancer cell proliferation and increasing apoptosis. It also helped produce higher levels of reactive oxygen species and inhibited the migration of the cancer cells. They also studied the genes involved in inflammation and immunity in pancreatic cancer and found that the combination drug regime activated a tumour-suppressor gene and downregulated another that is involved in drug resistance and decreased immunity.
Better clinical outcome
The team also addressed one of the major problems in pancreatic cancer known as desmoplasia, which is the presence of a rich collagen deposition around tumour. Collagen deposition leads to poor clinical outcome due to decreased delivery of the drug to tumor. “In fact, gemcitabine itself leads to desmoplasia thereby reducing its own effect. We found that the combination drug therapy reduced desmoplasia. The [multiple] sclerosis drug loosens up the tumour and aids gemcitabine to penetrate into the tumour thereby increasing the bioavailability of the cancer drug,” adds Dr. Harikumar.
The combination strategy showed no toxicity to the normal human and mouse cell lines thereby pointing towards the promising possibility of using this for the treatment of pancreatic cancer.
“Repurposing existing drugs cuts down the time taken to bring drugs to clinical testing. Moreover, using combination drugs can reduce the dosage of the drugs thus reducing side-effects,” explains Manendra Babu Lankadasari, PhD scholar at the Centre and first author of the study in an email to The Hindu.
