As the rocketing development of sequencing techniques, oncogene discovery enters an era of exponential growth, which supports many therapeutic targets for certain types of cancer. The statistical data reported is that 78% of cancer patients have one or more “culprit” mutations. Thus, establishing The pathogentic relevance of individual mutations is a major challenge to be solved.
Scientists can figure out the genetic rules of cancer in the support of diagnosis, risk stratification and individualized treatment, after large-scale cancer genomes have been sequenced. “We’re finding clinically relevant information in the tumor samples we’re sequencing for discovery-oriented research,” says Elaine Mardis, PhD, co-director of the Genome Institute at the School of Medicine. “Genome analysis can play a role at multiple time points during a patient’s treatment, to identify culprit mutations in the tumor genome and to determine whether cells carrying those mutations have been eliminated by treatment.”
Identify “Culprit” Genes for Cancer Treatment
Information of cancer genomes has been screened to identify specific culprit genes, which determine patients’ response to drug. In patients with advanced lung cancer, TORCH (Tarceva or Chemotherapy) investigators have found culprit mutations in EGFR that can be targeted by Erlotinib.
Additionally, Mardis has also found numerous culprit mutations in genes that have not previously been associated with breast tumors. A number of these genes have been identified in prostate, colorectal, lung or skin cancer, and leukemia. Drugs that target mutations in these genes, including imatinib, ruxolitinib and sunitinib, are already on the market.
Optimize Treatment
A series of mutations in the breast tumors, screened by GWAS strategies, have small-molecule inhibitor drugs that target defective proteins. For patients who are not responding to aromatase inhibitors, treatment options may encompass adding the indicated small-molecule inhibitor into conventional chemotherapy.
“We felt it was important to show that there could be therapeutic options available to patients who are resistant to aromatase inhibitors,” says PhD Mardis,. “As we move forward, we think sequencing will contribute crucial information to determining the best treatment options for patients.”
Reference:
The Next-Generation Sequencing Revolution and Its Impact on Genomics. Cell 2013;
155(1): 27–38