IIT Kanpur scientists provide insights into prostate cancer

Researchers at the Indian Institute of Technology Kanpur have established that a gene associated with jaw development in embryonic stages has a key role in helping people with prostate cancer survive its severe form. Prostate cancer is the world's second most frequent cancer and fifth leading cause of cancer death among men. In India, too, the incidence of prostate cancer is increasing.

The distal-less homeobox-1 (DLX1) gene has a critical role in body patterning, particularly in the formation of the jaw, nervous system and skeleton. The protein expressed by the DLX1 gene has ostensibly no role to play once the organs are fully developed. But scientists discovered high levels of the protein in people who are suffering from advanced and spreading stages of prostate cancer. What role it plays in the progression of prostate cancer, however, is still a mystery. In the West, DLX1 protein, which is detected through a urine test, is in use as one of the biomarkers of prostate cancer.

In a paper published in Nature Communications in September, the IIT Kanpur scientists, led by Bushra Ateeq, Associate Professor of Biological Sciences and Bioengineering, however, showed that the DLX1 may have a greater role to play than that of a simple biomarker.

"Some genes are highly expressed in certain cancers but do not necessarily have a role in the cancer development. But we have found that's not the case with DLX1. Apart from being a good diagnostic marker, it could also be used as a drug target," said Ateeq, who received the Shanti Swarup Bhatnagar Prize in Biological Sciences in 2020.

For several years, Ateeq's group has been working on unravelling biomolecules associated with prostate cancer in Indian patients. "Our studies not only confirmed the presence of DLX1 in prostate tissues of cancer patients, but also showed that it plays a significant role in the progression of prostate cancer," Ateeq said.

As part of their research, the scientists probed the reason for this over-expression of DLX1 in prostate cancer patients. They found significantly higher levels of DLX1 in cancer tissues provided by their U.S. collaborators – Nallasivam Palanisamy at the Henry Ford Cancer Institute, and Colm Morrissey at the University of Washington.

"We found that 60% of the prostate cancer patients harbour high levels of DLX1 protein, which drives tumour progression and facilitates metastases to bones and other organs," said Shakti Goel, a PhD scholar in Ateeq's lab and the first author of the study.

A significant finding of the study is that DLX1 can be a drug target. There are drugs, currently in clinical trials, which target molecular pathways that lead to a higher production of DLX1 in prostate cancers. Ateeq has shown that these drugs, when administered to mice, reduce DLX1 levels and the associated capacity to form tumours. Thus, the use of such drugs can lead to a better clinical outcome for about 60% of prostate cancer patients.