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Presidency couple improve anti-cancer drug

(From top) Poulomi, Sudipta and Shiladitya

New Delhi, June 26: Two young Indian scientists who were classmates at Calcutta’s Presidency College and pursued similar career tracks have tweaked an anti-cancer drug, making it more effective against tumours and less toxic to the body.

Their research, conducted at the Massachusetts Institute of Technology in the US, could lead to a superior, improved version of a common anti-cancer drug called cisplatin, which is effective against a range of tumours, but is fiercely toxic to the kidneys.

Poulomi Sengupta and Sudipta Basu and their colleagues have tethered cisplatin to a molecule of cholesterol and shown through studies on mice that the cisplatin-cholesterol hybrid doesn’t harm the kidneys and may work better against tumours than the original cisplatin. They have described their results today in the US journal Proceedings of the National Academy of Sciences.

“It’s a simple concept, but it dramatically changes the behaviour of cisplatin, a compound used in over 70 per cent of cancers,” said Shiladitya Sengupta, principal investigator at the laboratory for nanomedicine at MIT who directed the research.

The scientists used a concept called supramolecular nanochemistry in which the drug is modified to impart it a unique property to self-assemble into nanostructures of just the right size that cannot enter the kidney but are able to accumulate in large amounts inside tumours.

“The self-assembly process increases cisplatin’s size, enabling it to bypass kidneys and reach the tumours,” said Basu, who has returned to India and is now a faculty member at the Indian Institute of Science Education and Research, Pune.

Basu and Poulomi had studied chemistry honours at Presidency College, remained classmates during their master’s course in chemistry at the Indian Institute of Technology, Kanpur, before he left for a PhD in Germany and she moved to the US for another master’s. They got married in 2008, before she joined Basu at MIT in Shiladitya’s lab.

While at MIT, the couple collaborated with post-doctoral researcher Shivani Soni and demonstrated through mice models of breast and ovarian tumours that the cisplatin-cholesterol hybrid has a significantly enhanced anti-tumour efficacy.

Cisplatin is a widely used chemotherapy drug administered to patients with cancers of the oesophagus, lungs, stomach, prostate, bladder, and some lymphomas among other cancers. But its extreme toxicity on the kidneys also poses a threat to patients.

“Over the past 40 years, there have been only two more platinum-containing molecules since cisplatin that have shown good efficacy,” Shiladitya told The Telegraph. The increased anti-tumour efficacy observed with the cisplatin-cholesterol hybrid suggests that the molecular tethering trick could lead to the next generation of platinum-based drugs against cancer, he said.

The technology has been licensed to a company in India, Invictus Oncology, set up by Shiladitya and Raghunath Mashelkar, a leading chemical synthesis specialist and former director-general of the Council of Scientific and Industrial Research. Mashelkar, who is a visiting faculty at the Harvard Medical School, was involved in the synthesis strategy and is a co-author of the paper.

“It’s an enjoyable experience to work with and watch young people in a field where cutting-edge research promises to improve the quality of life of patients,” Mashelkar, who continues research at the National Chemical Laboratory, Pune, said.

Scientists expect that the cisplatin-cholesterol product could be ready for human clinical trials by 2015.