Those biochemically literate cancers

I love it when material from different classes comes together! This week, I did a presentation on drug resistance in my cancer genomics class looking specifically at a drug that targets a fusion protein that is a product of a chromosome translocation. Thinking back to the information storage property of DNA, one can easily see how having pieces of DNA from different chromosomes fused together combines two templates which are transcribed and translated into a single protein whose structure and hence function are different from either original protein. The protein  formed in this case was Bcr-abl an over active kinase which leads to leukemia.

Using bioinformatics, scientists have been able to come up with a structure of a drug (Gleevec) that fits into the active site of the kinase and binds it so it can no longer perform its phosphorylation function and the cancer can be slowed down. The unfortunate thing however is that the cancer cells (as if they know biochemistry) mutate residues that are important for electrostatic interactions between the drug and the kinase to uncharged ones , or replace small residues with bulky ones  creating an inability for the drug to bind and leading to drug resistance by the cancer cells.

I’m glad that concepts from different classes come together to give me a better understanding of varied concepts.