New Delhi, June 24: After three years of tweaking molecules, Indian biologist Shiladitya Sengupta has engineered one of the most effective known anti-cancer drugs to eliminate its toxic effects on kidneys, promising much safer cancer therapy.
The molecular engineering feat pulled off by Sengupta at the Harvard Medical School in Boston, and his colleagues in India and the US, may allow doctors to improve treatment against cancers of the breasts, lungs and ovaries.
The India-US research team has worked on a chemotherapeutic drug called cisplatin, the first choice of treatment against a range of malignancies, including cancers of the breast, cervix, lungs and ovaries.
Cisplatin destroys tumour cells, but also kills kidney cells. Doctors treating cancer patients with cisplatin calibrate the dose — keep it as low as possible — to avoid the side-effect on kidneys.
Now, Sengupta and his colleagues have substituted two molecular structures on the cisplatin molecule with a synthetic polymer. Studies on mice with tumours show that this polymer-cisplatin compound works just as effectively as the original cisplatin on tumour cells, but does not harm the kidneys. The scientists have described their research this week in the journal Proceedings of the National Academy of Sciences.
A molecule larger than 5 nanometres (nm) — five billionths of a metre — cannot enter the kidneys. While cisplatin is less than 5nm, the cisplatin-polymer compound is much larger, 80nm to 100nm, and thus has no effect on the kidneys.
This promises to eliminate the threat of kidney damage. Doctors could increase the dose of the cisplatin-polymer compound administered to patients without increasing the risk to kidneys, Sengupta told The Telegraph.
In one set of studies in laboratory mice with tumours, the scientists observed that therapy with cisplatin caused their kidneys to shrink to half the size. But mice that were given cisplatin-polymer compound showed no change in kidney size.
The anti-tumour effect of cisplatin-polymer compound was as effective as the original cisplatin. Sengupta said the nano-sized cisplatin-polymer molecule also has a stealth property that allows it to evade the human immune system and circulate in the body until it is picked up by tumour cells. This stealth property allows the drug to selectively accumulate inside tumour cells and destroy them.
The India-US team has discussed the possibilities of pushing this research towards clinical trials with doctors at the Brigham and Womens Hospital in Boston. Were hoping clinical trials will begin in about two years from now, Sengupta said.