In an attempt to further validate genetic mutations linked to cancer, Massachusetts General Hospital Cancer Center plans to start off genetically testing lung cancer patients, and eventually test all patients that come to the hospital with a positive biopsy or a tumor.
"Genetic fingerprinting is currently being offered to our lung cancer group," said Darrell Borger, co-director of Mass General's new Translational Research Lab where the genetic profiling will be conducted.
"Our goal is to offer tumor screening to all patients that enter the MGH Cancer Center, regardless of tumor location, in approximately one year," he told Pharmacogenomics Reporter this week.
The center — claiming to be "the first and only cancer center" to attempt to molecularly profile all cancer patients that present to the facility — issued a statement announcing that it has so far identified 110 gene mutations linked to the growth of various malignant tumors.
"This new and improved classification of cancers that we are doing is intended to give our oncologists more information about a patient's cancer, so they can treat it in a very specific way, thereby significantly increasing the odds of successful treatment," said Leif Ellisen, co-director of the translational research laboratory, in a statement.
Furthermore the gene analysis will allow doctors to prescribe "smart drugs" designed to block certain gene mutations and pathways that cause cancer tumor cell growth.
"By targeting tumor gene mutations with these smart drugs, doctors may be able to eradicate malignant cells without using traditional treatments like chemotherapy and radiation, which have significant side effects," the researchers said in a statement. "The lab's new tumor genotyping initiative should also expedite the time it takes to find the right drug for the right patient."
Borger did not specify which "smart drugs" doctors will prescribe using genotyping. However, Ellisen noted in a statement that in the case of lung cancer, since that is the first group of cancer patients to be genotyped in the lab, researchers suspect that a colon cancer drug shown to be efficacious in a particular genetic subpopulation may also be useful in lung cancer patients with the same gene mutations.
While Ellison did not name the drug, data from recent studies have shown that patients with metastatic colorectal cancer whose tumors carry the wild-type version of the KRAS gene are much more likely than patients with the mutated form of the gene to benefit from the monoclonal antibodies such as Amgen's Vectibix and ImClone's Erbitux [see PGx Reporter 06-04-2008] .
While neither drug is indicated for lung cancer, studies have show a marginal benefit in lung cancer patients when treated with Erbitux, and have not shown any benefit in lung cancer patients treated with Vectibix.
But targeting patients specifically with wild-type KRAS mutations, might experience better outcomes with these monoclonal antibodies, and this is exactly the kind of information Mass General's researchers are hoping to uncover at their new molecular pathology lab.
Mass General worked with Beckman Coulter subsidiary Agencourt to develop an automated method for extracting genetic material from diagnostic tumor samples, which will allow the lab to increase its sample processing capacity by 10-fold. The lab will use a multiplexed single-base extension method, which was developed to identify single nucleotide polymorphisms, to interrogate a number of somatic cancer gene mutations at once.
"We now have the capacity to process 100 diagnostic tumor samples per day," Borger said. "Additional robotics are currently being adapted by our laboratory to provide a similar increase in capacity at the level of our genotyping assays."
At the laboratory, it is expected that samples will be able to turnaround test results within two to three weeks. This is the turnaround time that is necessary, "in order for genotyping information to be useful to our clinicians in guiding initial therapeutic decisions with their cancer patients," Borger said.
Borger could not provide an estimate of how much it will cost to genotype all cancer patients at its laboratory, saying "the cost of the tumor screening is still being finalized." He added that the cost will be comparable to other routine clinical diagnostic tests.
Clinical diagnostic tests for cancer are not cheap, usually carrying a price tag of several thousands of dollars. It is unclear if health insurers in the state will cover the cost of testing. Mass General officials have made public comments suggesting that the hospital may absorb part of the cost and ask patients to foot the rest of the bill.
Despite the high cost and uncertain reimbursement environment, Borger focused on the long-term health benefits and cost savings genetic testing promises. "The potential for identifying the most effective treatment strategies from those that have little chance of success is expected to provide large cost benefits," he said.
While Mass General may be the first hospital to take on the challenge of genotyping all cancer patients, other cancer centers have similar projects on a smaller scale.
According to reports, Dana-Farber Cancer Institute genetically screens patients with certain melanomas to gauge whether they will be responsive to certain drugs. Memorial Sloan-Kettering Cancer Center is also said to be launching a program to genetically screen lung cancer patients in the coming weeks.