Life Science. New approach to cancer treatment

Cancer spreads in the body due to unchecked growth of diseased cells. But did you know there are some kinds of proteins that help cells, including diseased cells, die?

These death-hastening proteins, if left alone, would rampage through the body, killing even the good cells. What prevents this is another special type of ‘membrane proteins’ called VDAC (voltage-dependent anion channels) proteins. Meant to promote cell growth in general, the VDAC proteins act as gatekeepers, binding themselves to the pro cell-death proteins and inactivating them to help the cells live longer. This property, however, interferes with cancer treatment, because we want the death-allowing proteins to let the diseased cells die, but leave alone the good cells.

R Mahalakshmi, Associate Professor at IISER, Bhopal, is researching a way around this.

VDACs are of three kinds — identified as 1, 2 and 3. All of them function as gatekeepers and ion transporters, but it is the VDAC2 that can bind with and inactivate another protein that, if left alone, can allow a cell to die. Understanding VDAC2 has kept Mahalakshmi busy for much of her 11 years in research. “If we understand the characteristics of VDAC2, we can modify its behaviour so that it lets go those proteins that are pro cell-death,” she says.

Having the diseased cells die quickly by interfering with the VDAC2 function can make a world of difference to cancer treatment.

Mahalakshmi has pinpointed some unique molecular differences between the three VDAC proteins. Now she proposes to utilise these differences to elicit VDAC-specific function, so that the cell decides whether to live or die.

She broke down each of the three VDACs into individual segments and studied each segment. She then took some of the differences back into the protein and checked if there was a switch in behaviour. And, surprisingly, some of the characteristics did change.

VDAC2 has 11 extra amino acids compared with the other two. She removed these 11 amino acids and tested the protein and it behaved like VDAC1, which does not have these 11 extra acids. “Now I will be able to target the differences to let each VDAC do the work we desire,” Mahalakshmi told Quantum .

Here’s how she proposes to achieve the end goal: When two proteins interact with each other, they need an interaction surface. Mahalakshmi aims to find a way to target the VDAC2-specific interaction surface so that it is no longer available. “Without the surface, the interaction is not possible, leaving the binding partner free to kill the cell.”

The trick, however, is to target only cancer cells and not the rest, since all have VDACs.

This is possible because cancer cells usually have biomarkers on their surface. Mahalakshmi plans to develop potent VDAC-specific peptide-based drugs.

To deliver these drugs effectively and selectively, she plans to target such biomarkers that are unique to cancer cells. The hope is that by adding redundancies and layers of protection, only cancer cells will be selectively targeted and killed.

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