Thursday, February 28, 2019

How does cancer treatment based on genomic data differ from standard techniques, such as chemical therapy?

First of all, to understand the reason behind the tailored therapy against cancer, you need to understand the causes of cancer. Although it is a widespread definition that Cancer is a mass of cells with infinite growth potential, but it is the genome wherein the reasons behind this potential can be found. The current decade 2005 onwards witnessed a massive revolution as the sequencing technologies developed in almost geometric progression. Genomics came a long way from Sanger sequencing in the earlier era to the current Illumina and other next generation sequencing platforms.
The Genomics approach towards the cancer has led to the understanding of the progression of several Cancer types by studying the mutations termed as Driver and Passenger mutations in the genome. We know that there are several classes of genes that need to be mutated for cancer to progress. These are tumor-suppressors, genes that protect our cells from cancer, so they need to be inactivated by mutations, and oncogenes. These genes need to be overactivated by mutations, but again these are just mutations, just changes in DNA. Or, for example, amplifications of the same gene: it’s not mutated, but now instead of one copy of the gene you get ten copies of the gene. And that’s enough to make the cancer cell. So the mutations may not really be the changes in DNA sequence, there can be certain aberrations in the intricate regulation machinery of these genes causing an inactivation of the tumor-suppressors or causing ectopic expression of the oncogenes.
But mutations cannot really hit at specific positions. That’s the essence of Darwinian theory of evolution that mutations happen at random. So that means that cells are sitting and waiting for the next mutation, and now we’re talking about cancer, so cancer cells are sitting waiting for the next mutation to happen. When this mutation happens in one of the cells, the cell will take over the population and will form sort of a new layer of cancer, if you wish. In biology we call this clonal selection,i.e. a particular population of cells becomes dominant.
However, the cells are sitting and waiting for the right mutation, so they are getting random mutations. And they are generally getting a little bit sick of this random mutations. These mutations are collectively called ‘passengers’. So those mutations that drive cancer progression are called ‘drivers’ and others are called ‘passengers’. It’s is generally "believed" that passengers are neutral, they play no role in cancer. Because drivers are usually the same in different patients, but passengers are all different.
So one of the major center of focus of current cancer genomics is to profile the cancer genome from several patients and based on the specific passenger and driver mutation, tailor a patient specific therapy. Moreover, this was needed given the highly heterogenous nature of the cancer. By far several disorders in medical history could be diagnosed and treated by particular fixed symptoms and targets, but in cancer that is not the case. Moreover it is now also observed that the differential response and reversion ability of cancer patients to the radiotherapy and chemotherapy is because certain patients are genetically predisposed to do so.
By far the 1000 genome project has given us only the exome sequence data, so this just gives us information about the driver and passenger mutations from the coding regions of the cancer genome which is far from less compared to the complete genome. Albeit, this data too has led to beliefs that genomics has lot of potential to determine the cancer therapy for every patient based on his genetic predisposition. Hence given the level of complexity Cancer possesses, Genomics by far gives the best possible approach to design very reliable therapies.

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