Genetic Mapping of Cancer Proves to be an Extremely Complex Process

Scientists have spent years working to improve the treatment of cancer and are now working with genetic mapping in hopes of a breakthrough in fighting the disease. Experts have now thoroughly examined every gene in tumors from two of the most difficult-to-treat cancers, glioblastoma, which is the most aggressive type of brain tumor and pancreatic cancer. These fatal cancers claim the lives of victims within only months of diagnosis.

Genes going awry and mutating in many different ways, which are not normal to the body's form and function, cause cancer. Mapping the genetic mutations linked to cancer could lead to more closely matching appropriate treatments to individual patients, pave the way for the creation of new diagnostic tests, and maybe even guide the development of new drugs for treatment.

Two groups of researchers analyzed massive quantities of genetic information from tumor samples in an effort to record the many different variations of cancer. However, during the analysis, the researchers found that cancer is much more complicated than anyone could have possibly guessed. While the group had expected to identify certain key genes that were frequently mutated, they found not only a much larger number of mutated genes, but also found that each gene mutated in a smaller fraction of the tumors, giving an answer as to why a cure is unlikely after a tumor has spread.

Two separate papers were published in the journal Science on pancreatic and brain cancer that resulted from the private cancer-genome project led by researchers at Johns Hopkins. Victor Velculescu of Johns Hopkins Kimmel Cancer Center and a co-author of two papers said, "We used to think there was one enemy that was well-defined, but now we know there are lots of little enemies." A much larger third study is published in the journal Nature, also involving glioblastoma, and has been funded by the U.S. National Institutes of Health.

Researchers usually begin with a general idea about which drugs may destroy tumors and then test them in labs and then move forward to animal testing before finally conducting trials with human subjects. Drug companies have introduced targeted anticancer drugs that attack specific targets of a tumor's cellular machinery such as Herceptin, for breast cancer, and Gleevec, for a type of leukemia, which have generated a keen interest in the industry.

The new research indicates, however, that most brain and solid tumors are very different. According to Bert Vogelstein, cancer researcher at Johns Hopkins, and co-author of the Science papers, "It is extremely unlikely that drugs which target a single gene like Gleevec will be active against a major fraction of solid tumors. Instead of screening for drugs against single proteins, our work suggests that it may be more productive to screen for drugs that act against core pathways."

Building a library of mutations for different tumors could be a potential new way to treat cancer and could also allow doctors to quickly diagnose a tumor before it grows too large to be surgically removed. Since DNA and cells are frequently dislodged from early-stage tumors and move into the bloodstream and body fluids, tests based on mutations could detect the presence of a tumor before a patient even shows symptoms.

The team sequenced over 20,000 genes in cells from 24 patients with advanced pancreatic cancer and 22 patients with glioblastoma. They found the typical pancreatic tumor had 63 genetic mutations, while the average brain tumor had 60. However, they found only 12 pathways that were abnormal in most of the tumors. One downside of this is that the pathways are also responsible for key biological functions and disrupting them could trigger severe side effects.

The Science study on glioblastoma, which is the type of cancer Senator Edward Kennedy was diagnosed in May, yielded the discovery of a new gene, IDH1, never before linked to cancer. Patients with IDH1 mutations had a longer survival time than the typical brain tumor patient, suggesting a new treatment strategy. According to Dr. Victor Velculescu, also of Hopkins, "Glioblastoma multiformes used to be thought of as one disease. It is now clear they are two."

The Nature study was conducted on over 200 samples of glioblastoma the Cancer Genome Atlas Research Network. The study was launched in 2006 and is a three-year pilot program centering on ovarian, lung and brain cancer. The plan is to expand the analysis to include mutations found in the 50 major types of cancer.