Columbus, OH: A research effort started by two young scientists in Calcutta 25 years ago and carried forward in a US university may lead to a new and inexpensive way of dramatically improving the efficacy of cancer chemotherapy.
Sujit Basu was a fresh medical graduate and Partha Sarathi Dasgupta was pursuing a PhD at the Chittaranjan National Cancer Institute in 1986 when they found themselves riveted to a chemical called dopamine that mediates signals between brain cells.
The researchers, who continued to collaborate after Basu moved to the US, have now shown that dopamine can boost the efficacy of anti-cancer therapy by repairing defective, leaky blood vessels that surround almost all tumor cells.
“Defective blood vessels pose a big challenge to chemotherapy,” said Basu, who is now a medical oncologist at the Ohio State University, Colum-bus.
Blood vessels serve as conduits for anti-cancer drugs, but the faulty vessels that sprout around tumors lead to decreased blood flow and low oxygen levels in tumor tissues. This, Basu said, prevents anti-cancer drugs from reaching optimum levels where they are needed the most.
In their new experiments, the re-searchers have un-raveled a part of the genetic and molecular mechanisms through which dopa-mine repairs blood vessels. The results are to appear in the journal Proceedings of the National Academy of Sciences on December 6.
“Dopamine corrects the underlying architecture - the brick and mortar of blood vessels,” said Dasgupta.
“This effect leads to improved blood flow and higher oxygen concentration in tumor tissues, which are conditions in which chemotherapy drugs work better,” said Basu.
The researchers have observed that dopamine treatment can nearly double the concentration of chemotherapy drugs in human colon and prostate tumor tissues that have been experimentally transplanted into mice.
Debanjan Chakroborty and Chandrani Sarkar, two former PhD scholars at the Chitta-ranjan National Cancer Insti-tute, who are now at the Ohio State University, contributed to the design of the new experiments, performed with their colleagues Hongmei Yu, Jiang Wang and Zhongfa Liu.
Although some drugs that promise to tackle the problem of defective blood vessels via other mechanisms are either already available or under evaluation, Basu said, most of them are “very expensive.”
But dopamine, a neurotransmitter, is an inexpensive drug that has been widely used for decades in the treatment of neurological diseases such as Parkinson’s disease and other conditions, Dasgupta said.
“This concept will need to go through rigorous clinical trials, but dopamine is already widely used, so we could expect it to move into clinical trials quite fast,” said Pramod Julka, professor of clinical oncology at the All India Institute of Medical Sciences, New Delhi, who was not associated with the study.
Basu and Dasgupta believe they are lucky that their collaboration has endured for over two decades and even led to medical applications in other areas. Their initial work on dopamine has been evaluated for applications to treat endometriosis, a gynecological condition.
The two researchers bring complementary skills into their collaboration: Basu is a doctor and Dasgupta is a basic scientist. “This way, the science remains connected to applications,” Dasgupta said.
Clinical trials that add dopamine to chemotherapy, Basu said, could be just months away.
