The Role of Cancer Genome Profiling In The Care of Stomach Cancer
For cancer patients, caregivers and providers, there is good reason for enthusiasm about the potential research into the cancer genome to help guide more effective cancer therapy. In stomach cancer, there is already a role for specific testing in the care of patients with advanced or Stage 4 disease. There are, however, a number of questions and limitations that need to be considered regarding genetic tumor profiling and how best to proceed in terms of one’s therapy.
As background, the reason we are investigating the cancer genome follows our understanding that a key cause of human cancer is the accumulation of DNA changes or mutations in cells of our bodies. These DNA mutations lead to changes in how our cells function. These particular gene mutations can aberrantly activate specific growth-promoting genes. In many settings, these hyper activated genes can be inhibited by existing or emerging drugs. It is the hope that tumor profiling may help figure out which genes are activated in each tumor, providing ideas about what may be optimal therapeutic targets. [As an aside, it is important to note that the genomic testing that is part of tumor profiling is typically NOT the kind of genetic testing that looks for gene changes that we inherit from our parents or pass onto our children. Rather, most genetic alterations in tumor profiling that guide therapy are looking for mutations that are present in the DNA of cancer cells but not in the DNA of normal cells in our bodies.]
So what can genomic profiling of tumors do? The hope is that genomic profiling of tumors will ultimately help guide cancer treatment. That said, the vast majority of the gene profiling has not yet been shown to effectively guide better therapy (in both stomach cancer and many other cancers). Simply put, if we had tests that we know could effectively guide therapy for patients, we would routinely offer those tests. For example, we have such a test in the care of stomach cancer. Patients with Stage 4 stomach cancer are tested for a gene called ERBB2 (or Her2) and if tumors are found to be ERBB2/HER2 positive, those patients are offered therapy including a specific HER2 inhibitor.
But beyond HER2 there are other gene mutations that we have found frequently in stomach tumors that provide hints as to new candidate targets for therapy. That said, for these new emerging alterations we do not yet have evidence that using specific drugs to inhibit these emerging targets will improve patient’s outcomes or survival. Since we don’t have evidence that these tests and the therapies are effective yet, this explains why these tests are not routinely offered to patients. However, we are hopeful that future research will demonstrate that using new therapies that attack specific targets that we are now finding through cancer genome profiling will help patients. For now, it is reasonable to state that (outside of HER2), the results of tumor profiling typically do not have a clear and definite implications for what steps a stomach cancer patient should take. However, these profiling data may be useful to help one decide upon which of a number of clinical trials may be most reasonable to pursue. That is, if the tumor profiling shows a particular hyper activated growth promoting gene, it is worth considering a trial of a drug that blocks this particular gene. In occasional cases, profiling may suggest that a drug that is known to work well in another type of cancer may be helpful for a specific patient with stomach cancer.
With the caveats that it is not unreasonable that genomic tumor profiling is not yet standard-of-care, there are still opportunities to pursue testing for those interested. There are several large academic medical centers that do perform such testing on many patients as part of their own research efforts. Beyond testing at these centers, there are increasing numbers of private companies that are offering tumor profiling as a service. There are a number of new companies entering into testing and it remains to be seen what the comparable quality of sequencing and data analyses are from these different companies. It is also the case that many patients’ insurance would not cover the cost of testing. Indeed, insurance companies typically will pay for established and standard therapies and tests with demonstrated efficacy but they often will not pay for research or testing that is not standard. In some cases, when genomic testing is performed as part of a research program, the costs of testing may be included as part of the research.
Given all of this complexity, it is not possible to make a simple and firm recommendation about what any patient should do. It is clearly not at all unreasonable to pursue tumor profiling even if the results will not be easy to interpret or act upon. Even though they would not guide standard therapy, profiling can help to guide decisions about specific clinical trial options. Your treatment team can help you talk about these issues. But ultimately, we and others are now pursuing research into these areas because there is not yet a right or wrong answer to this question.
By: Adam Bass, MD
Assistant Professor, Department of Medicine, Division of Cellular & Molecular Oncology
Harvard Medical School and Dana-Farber Cancer Institute
July 20, 2015