Friday, June 3, 2011

Advances in Cancer Genomics

The genetic basis behind cancer formation implies that to fully understand the disease and effectively treat it, we must first gain an extensive knowledge of the driving genetic mechanisms which bestow upon cancer its defining characteristics. Beginning with the ambitious effort put for by the Human Genome Project, gene sequencing technologies have seen enormous improvements in speed, accuracy and cost effectiveness.

This advance in our ability to unveil the inner workings of the human genome has pushed cancer research to the next level. The decreasing cost and amount of time required to sequence DNA has brought upon the birth of numerous massive DNA sequencing studies in the field of cancer biology. For instance, The Cancer Genome Atlas (TCGA) is an study begun in 2006 and funded by the NCI and NHGRI which is collecting a massive sample of complete somatic mutation spectra for 20 types of cancer. In addition, catalogs and databases such as COSMIC which collect and refine this data have contributed greatly to our increased understanding of cancer genomes. The success and implications of this flourishing field of research give hope that treatment is set to improve in the near future.

Already, sequencing projects have begun to yield promising results. A news article from the National Cancer Institute (NCI) outlines the promising findings of a whole-exome sequencing project for melanoma. According to the article, the protein coding sequences (exome) of 14 metastatic melanoma tumors were sequenced and compared to look for potential genes which were involved in the formation of melanoma tumors. The researchers identified 16 genes as driver mutations in melanoma, only one of which (BRAF) had ever been identified as contributors to melanoma formation. In this manner, extensive knowledge of the drivers behind the formation of different cancer types is being collected around the world.

This expanded knowledge could provide scientists with novel targets for chemotherapy. For instance, one of the new driver genes identified in the melanoma sequencing effort, TRRAP is an activator protein involved in the function of pathways crucial to proliferation such as P53, and MYC. Mutation of this oncogene could alter these pathways and contribute to cell proliferation and immortality. According to the article, discoveries such as the TRRAP gene represent opportunities to disrupt tumor growth.

However, the mutation only occurred in 4 percent of cases, representing limited probability for widespread application of a drug targeting this particular protein. Is it possible that although we are gathering a vast amount of information, we are missing something or looking in the wrong place? It would seem that there are an enormous number of ways to alter any given pathway. Maybe if something could be devised that effected the pathway as a whole instead of functioning on an individual protein basis, drugs could become more effective. Or instead, perhaps another facet of cancer besides its many defective signaling pathways can be targeted which is common in all cancers and not just a few cases. The lack of truly definitive commonalities does not mean that sequencing is pointless, but is a little disheartening.

Granted, it takes a long time to convert this raw information into viable treatment options, but the wealth of new data makes it all the more likely that the newest drugs will be increasingly effective. In addition, with the fast pace of advancement in sequencing techniques, the possibility of sequencing tumor genomes on a patient by patient basis is drawing closer to reality. This would allow an unprecedented level of accuracy in both diagnosis and treatment, further enhancing our ability to combat the disease.