Could this made in India 'smart' cancer drug make chemotherapy safer?
Indian scientists have developed RK-251, a prodrug designed to activate inside cancer cells. Experts say the early findings are promising, but human trials must establish safety and effectiveness.
Cancer treatment has made major advances, but chemotherapy remains an important part of treatment for many cancers – a disease growing fast worldwide as well as in India. And the basic strength of the therapy is also one of its biggest limitations: many chemotherapy drugs attack rapidly dividing cells, but they cannot always distinguish cancer cells from healthy cells that also divide quickly.
This can lead to side effects such as nausea, fatigue, hair loss, mouth sores, low blood counts and increased risk of infections.
Now, Indian scientists have developed a potential new approach that aims to make cancer treatment more selective. The drug candidate, called RK-251, has been designed to remain largely inactive in normal cells but switch on inside cancer cells.
The research was led by scientists from the Institute of Advanced Study in Science and Technology (IASST), under the Centre’s Department of Science and Technology, and the Indian Institute of Technology (IIT), Guwahati.
The work is significant because it attempts to tackle two long-standing problems in cancer treatment at the same time: damage to healthy cells and resistance to treatment.
As per the World Health Organisation – International Agency for Research in Cancer (WHO-IARC)’s report for 2024, released last month, India had registered 15.6 lakh new cancers in India that year while 33 lakh people diagnosed over the previous five years were living in the country in 2024.
WHY CHEMOTHERAPY CAN BE DIFFICULT
Chemotherapy remains useful because it can kill cancer cells, slow their growth, reduce the risk of recurrence and, in some cases, help cure cancer. But because many chemotherapy drugs also affect healthy, fast-growing cells, patients can experience a range of adverse effects. The severity varies depending on the drug, dose, cancer and individual patient.
This is why researchers have increasingly focused on treatments that can distinguish tumour cells from healthy tissue. Targeted therapies, immunotherapies and other precision approaches are designed to exploit biological differences between cancer and normal cells.
But even targeted treatments can have side effects and cancer cells can develop resistance to them.
Treatment resistance is particularly challenging. A tumour is not made up of identical cells. Some cancer cells may naturally be less sensitive to a drug, while others can acquire changes that allow them to survive treatment.
The surviving cells can then multiply, allowing the tumour to return or continue growing.
This is where RK-251's proposed mechanism becomes particularly interesting.
Dr Mandeep Singh Malhotra, senior oncologist with Art of Healing Cancer and CK Birla Hospital, said, “This drug primarily is a prodrug which gets activated in cancer cells whereas in normal cells it does not.”
In simple terms, a prodrug is a compound that is administered in a relatively inactive form and is converted into an active drug under particular conditions inside the body.
RK-251 has been designed to take advantage of a feature that is more prominent in many cancer cells – elevated levels of reactive oxygen species (ROS).
HOW THE SMART DRUG WORKS
According to the study on the drug published , when RK-251 enters a cancer cell, high levels of ROS trigger its activation. The process releases an anticancer compound called NBDHEX, which then acts on proteins that cancer cells use to survive and resist treatment.
The idea is therefore different from conventional chemotherapy: rather than delivering an active cytotoxic compound indiscriminately and relying on differences in sensitivity between cancer and healthy cells, RK-251 is designed to become active primarily where the biochemical environment is favourable – inside cancer cells.
Dr Malhotra said the approach could potentially help overcome chemotherapy resistance because the activated drug acts on “the proteins and the pathways which will cause chemoresistance.”
He added that because the drug is not expected to be activated to the same extent in normal cells, “adverse effects would be limited.”
Preclinical experiments found that RK-251 showed strong anticancer activity against MDA-MB-231 triple-negative breast cancer cells, while having much less effect on non-cancerous cells.
Researchers also tested the compound in zebrafish embryos, where they found no obvious signs of toxicity and observed the expected fluorescence in the presence of ROS.
Dr Ankit Jain, medical oncologist at Indraprastha Apollo Hospital in Delhi, described the findings as promising but stressed the current stage of development. “RK-251 is at the preclinical stage currently which hasn’t been tested in humans,” he said.
He noted that the preliminary studies suggest “selectively lesser effects on non-cancerous cells”, potentially offering more selective action than conventional chemotherapy.
The distinction is crucial.
The drug has shown promise in laboratory and animal-related preclinical work, but that does not establish that it is safe or effective in people. Human clinical trials will have to determine the appropriate dose, safety profile, effectiveness and whether the drug can actually reduce the toxicities associated with chemotherapy.
WHY IT MATTERS FOR THE COUNTRY
The potential significance of such research comes against a growing cancer burden in India.
Tobacco-related cancers accounted for the largest broad category, while gastrointestinal cancers and breast cancer also represented substantial shares of the projected burden.
With more people requiring cancer treatment, improving not just survival but also the experience and tolerability of treatment is increasingly important. A therapy that can selectively attack tumour cells while sparing healthy tissue could potentially reduce treatment-related toxicity and make prolonged cancer treatment easier for patients.
It could also have implications for cancers that become resistant to standard therapies. Cancer resistance is already a major challenge, with resistant cells able to survive treatment and drive relapse or progression.
But experts caution against calling RK-251 a replacement for chemotherapy yet.
The findings, so far, are early and comprehensive clinical trials have to be done before the drug can be considered for cancer treatment.