Fight against cancer

Cancer cells are just like any other cells in our bodies. But, there is a critical difference: they turn into parasites. They do not work as they should and do not perform their designated function but only feed and divide. How does one fight out-of-control cells that look just like normal cells? Unlike the fight against regular disease-causing agents like bacteria and viruses, we cannot use drugs, because cancer cells are too similar to normal, healthy cells. Drugs capable of killing cancer cells often kill a lot of normal cells in a swathe of indiscriminate toxicity.

Cancers are insidious diseases that often creep up on patients, catching them unaware. As of now, most available methods of cancer detection involve blood tests, expensive CT or MRI scans and invasive procedures such as tissue biopsies. Unfortunately, these available methods frequently fail to detect cancers in the early stages. Since early and dependable detection of unnatural tissue growths, or ‘malignancies’ is the key to successful treatment, research is currently concentrated on developing newer and better methods of early cancer detection.

Nirmalya Ghosh, of the bio-optics and nanophotonics group at IISER-Kolkata, has been working on developing a method to detect cancer in its early stages, using an unusual tool — light. Cells are very complex, and scatter light that falls on them. Nirmalya and his team have shown that developing cancer tissues scatter light differently from normal, healthy cells. What is truly exciting about their unique light-probe based method is that it is more sensitive and accurate in detecting early stages of cancer than conventional methods such as MRI scans. Nirmalya’s group are now designing a suitable fibre optic probe to develop a cancer-screening setup in hospitals and clinics. Although the focus of this group’s work has been on detecting oral and cervical cancer, there is hope that this new technology can be used to catch early signs of other developing cancer types.

New targets for an old war
In bacterial, viral or worm infections, the biological processes of the invading organisms are so different from ours, that we can confidently use antibiotic drugs to selectively kill the disease. But what do you do when the ‘enemy’ is a part of your own body that’s gone rogue?

One of the hallmarks of cancer cells is their rapid division. Most conventional treatments use this factor to target cancer — radiation therapy and cell-division inhibiting drugs. However, an aftermath of such treatments is an unintended flood of toxic side effects. As the drugs and radiation kill cancerous cells, they also decimate normal tissues such as the stomach lining and skin, which also divide rapidly to maintain their function. This is why information on the molecular biology of cancer cells and their differences from normal cells is crucial — as the differences can help create effective treatments for this group of disorders.

A recent work in Annapoorni Rangarajan’s lab at the Indian Institute of Science (IISc) has identified two new proteins that are potential targets to limit the spread of breast cancers. Cancers spread when cells that are normally confined to one area break free and spread to other organs, through a process called metastasis.

Detaching from the support structures in their ‘home’ area causes these cells to undergo a period of stress that activates an enzyme called AMP-activated protein kinase (AMPK), which in conjunction with a protein, PEA-15, enhances the survival of these cells. Inhibitors of AMPK and PEA-15 therefore have immense potential as therapeutics in treating breast cancer.

Apart from this, a collaborative effort between two labs at IISc has identified a two-drug cocktail that may be another weapon in our arsenal against breast cancers. The therapy is a combination of an antibody against the Notch protein and a small molecule inhibitor against Ras.

Improving our weapons
In another part of the IISc campus, more breakthroughs in cancer treatment are being engineered. Two different groups have designed new anti-cancer therapies: one, a drug that could stall DNA repair in cancer cells was developed in Sathees C Raghavan’s lab; the other, developed by Akhil Chakravarty’s group is a trio of compounds that could destroy cancer cells when activated by light.

In 2013, Sathees’ group discovered SCR7, the first biochemical inhibitor of DNA Ligase IV, one of the key components required for repairing DNA in cells. Inhibition of Ligase IV led to killing of cancer cells, while sparing normal cells – this was because, there was higher amounts of Ligase in cancerous cells. SCR7 was found to be effective in mice. Continued research on this drug in collaboration with Jinu George from Sacred Heart College, Kochi has created a better form of SCR7, created by encapsulating SCR7 in a polymer. Called “ESCR7”, the new molecule is five times more efficient in destroying cancer cells than its predecessor, and represents an important milestone in the contribution of Indian science to cancer therapy.

Another group headed by Akhil Chakravarty’s have designed novel compounds in a unique form of anti-cancer therapy called PDT or Photodynamic therapy. It is emerging as a much safer alternative to chemotherapy or radiation, as it allows better selectivity in targeting cancer cells. In PDT, drugs called “photosensitisers” are injected into tumours and target the cancer cells’ energy factories, the mitochondria. The compounds accumulate within mitochondria and are inactive unless exposed to light of a specific wavelength, which activates them to produce special charged molecules called reactive oxygen species. These destructive molecules eventually kill cancer cells from within. One of the compounds, dubbed FPBP, is a promising candidate for PDT as it shows a 12-fold increase in cancer cell
toxicity when exposed to light.

According to the India Cancer Research database, there are 453 registered investigators in India who currently work on oncology. It is hoped that in future, Indian research will continue to keep up and perhaps surpass its current contributions to innovative therapies against cancer.