Scattered amongst the letters of genetic code in a tumor cell are telltale mutations and DNA alterations that spur its malignant activity. But there are billions of letters of code and each patient’s cancer is different, with its own particular genetic changes. These changes may dictate how it behaves, how aggressively the cancer progresses, and it may spell out which molecular weaknesses might be successfully attacked with treatments.
Technology like the OncoPanel platform of Dana-Farber’s Profile research program can rapidly decipher the DNA code of 400 cancer-related genes in an individual’s tumors, detecting mutations, missing or extra copies of genes, and other changes. But it’s a process that generates massive volumes of digital data – data which mean nothing until processed and analyzed. Only then, may researchers and oncologists be able to prescribe a precision treatment to target the specific mutation. This is the goal of precision cancer medicine, but it’s often a needle in a haystack search.
Dana-Farber’s Chris Sander, PhD, founded and directs the new cBio Center at DFCI, along with Ethan Cerami, PhD, who leads the Knowledge Systems Group in the Center, to help researchers mine the genomic data, using a user-friendly web-based tool they developed called cBioPortal for Cancer Genomics.
The cBio Portal software digests the data and presents it in diverse visual formats that help investigators detect patterns of abnormalities across groups of patients and cancer types.
With cBioPortal, a researcher can tap into the Profile tumor base of nearly 8,000 genomic tumor profiles and rapidly compare the mutation pattern in one patient’s tumor to those of hundreds of other patients. Some cancers with certain mutations might have an approved drug targeting those changes; finding the same mutations in other tumor types may lead to new trials of that drug. “We will be able to use cancer genomics to define groups of patients who might be eligible for new kinds of genomically informed clinical trials,” says Sander.
The cBioPortal analysis tools can also help scientists sift genomic data for clues to why a few patients in a clinical trial had dramatic responses to a drug that had little benefit for the majority of other patients. The cause of this “exceptional response” may be a previously undiscovered mutation that made the tumor vulnerable to the drug – and cBioPortal analysis of genomic profile data may help scientists discover it.
The Center’s Knowledge Systems Group has also devised a clinically oriented tool called MatchMiner. “Clinicians use it to recruit patients for clinical trials,” Cerami explains. “They look in the Profile database for patients whose tumors’ mutations match targeted drugs in available clinical trials, and they can have MatchMiner notify them when appropriate new patients are identified.”
The scientists are now working on tools to enable oncologists and patients to sit down together and use MatchMiner to search for clinical trials of drugs targeted to their cancer’s specific mutation pattern.