A new way to analyze the genomic data of tumors may allow clinicians in the future to treat each individual’s case as an individual disease.
Cancer is one among the most deadly diseases. Many cases of cancer are subtle and may go untreated for long periods of years. Recent clinical research can certainly claim some noteworthy victories. Regular monitoring, either by radiography, or via lab tests for specific biomarkers, has brought many breast and prostate cases within the limits of treatment. A vaccine, which is now available from family doctors, has great potential to reduce rates of human-papillomavirus. Some strains have been linked to cervical cancer. According to the American Cancer Society there are more than 14 million cancer survivors in the United States, and that number will increase over the next decade.
However, for many, the prospect of ever being diagnosed with cancer is still frightening. Perhaps it’s time to think about a new approach. Instead, trying to face the invader with chemotherapy, radiation, surgery or other medical weapons, on every battlefront, medical researchers could launch sneak attacks from a different viewpoint–that being, the perspective of gene mutations that actually drive tumor growth. The Broad Institute, which is a collaboration between Harvard University University and Massachusetts Institute of Technology, and the Dana-Farber Cancer Institute at Harvard Medical School are doing just that.
The pressed fraction of the gene includes the 1 to 2 % of DNA that encodes the specific instructions for creating proteins. In a May paper published online by Nature Medicine, a team headed Levi Garraway (and Gad Getz) announced that they had developed a method to sequence all 16 exomes of patients with tumors.
Although it is not unusual to study genetic mutations that can lead to cancer, these studies have been limited in scope. They have focused on only a handful of hotspots (that is, areas of the DNA sequence which have shown evidence of being clinically relevant for the type of disease under investigation).
However, fresh-freezing the panels is still the best method of preserving them. This technique has also limited the availability of samples in places that could keep them in optimal conditions. The Nature Medicinepaper, which is innovative in both the way it sequences the entire exome and does not select hotspots, as well as technologically. “This paper is intended for proof of concept in start-to-finish soup-to-nuts, whole-exome ordering,” says Nikhil Wagle a medical oncologist at Dana-Farber who is also an associate member with the Broad Institute.
The authors created an algorithm that would help them sort through all the data from their full on sequencing approach. Eliezer VAN ALL, also at Harvard Medical School/Dana-Farber, is the paper’s initial author. Although whole-exome sequence was appealing, it has never been validated.
It was revealed that the algorithm only identified a very small number of genetic alterations related to various types cancers. These alterations (point mutants, small additions/deletions, or changes of the number or gene copies) appeared repeatedly regardless of whether samples were from lung or gastric cancer. These were designated driver genomes by researchers.
Wagle says, “In every form of cancer, there are some drivers genes and many passengers genes that go along for a ride but might not instigate anything themselves.” With precision medicine, clinicians will focus their treatment on the target genes of a patient with cancer and not necessarily the parts of their body showing clinical signs. The key to choosing the correct treatment is the anatomic classification. Melanoma for example cannot be treated with techniques appropriate for ovarian. Wagle says that the genomic data will be “layered over top” of this information. The more information you have, the better. The future will see treatments that are more customized and refined based on individual patients’ genomic data. Van Allen explains that there is now evidence of genomic diversity among patients with the same anatomical type of cancer. However, this can also be seen within a single patient.
Wagle says precision medicine, the process of finding out which genes are responsible for a cancer’s aggressive treatment, is “in theory” possible. He and his collaborators are so eager add to their data, that they have started crowd-sourcing the collection. Researchers from all parts of the globe are invited to send their nominations. Wagle continues, “Officially, we require certain levels of evidence. And, we spell that out on our site.”
Dana-Farber’s Broad Institute is not the only one who wants to look beyond the traditional broad-brush approach. This was a method that gave few other options for treatment when a patient didn’t respond to the usual, reliable but generic therapies. Many cancer centers throughout the country are using molecular information to optimize treatments for patients based on their genomic profile. These are just some of the major research institutions that have taken on these types of initiatives. Craig Thompson, president Memorial Sloan Kettering Cancer Center, expressed the hope of many of his coworkers when he said, “We are moving away from the notion of treating cancers as different types and towards treating each patient’s cancer as an individual disease.” . . . “heralding in what will truly become a new generation of precision medicine.” Sandra J. Ackerman
