A Conversation with James Patrick Solomon, M.D., Ph.D.
Jim Solomon is Assistant Director of the Clinical Genomics Laboratory and Assistant Professor of Pathology and Laboratory Medicine at Weill Cornell Medicine (WCM), and Assistant Attending Pathologist at NewYork-Presbyterian (NYP).
He grew up near Allentown, Pennsylvania and earned his undergraduate degree at Princeton University, his medical degree from the University of California at San Diego (UCSD), and his doctorate from the Scripps Research Institute.
Jim now splits his time between academic and clinical medicine. Using the next generation sequencing panels Oncomine and EXaCT-1, he provides important molecular information that helps diagnose cancer and informs treatment options for dozens of patients a week. He’s also developing new assays in the clinical genomics lab that will help characterize tumors beyond conventional DNA sequencing.
Jim and his wife lived in southern California for 12 years, before they moved back east to be closer to their families, and for Jim to participate in Surgical Pathology and Molecular Pathology Fellowships at Memorial Sloan Kettering Cancer Center. He started at WCM in July of last year.
We hope you enjoy learning about his work and current research interests.
When you were growing up did you always want to be a doctor?
I was always interested in science and the molecular basis of disease. I was really interested in chemistry in high school, and majored in chemistry in college. Then when I started looking at careers, the medical scientist training program was attractive because it was sort of a combination of medicine and science, and you could conduct research that was more relevant to patient care.
During medical school training I discovered that I loved pathology because it really appealed to my interest in the science behind the disease. I enjoyed working in the laboratory behind the scenes to objectively diagnose the disease a patient had and to provide information on how to treat them.
Why did you choose to work at WCM and NYP?
I was really attracted to the expanding molecular pathology program and how it integrated research into patient care. On a more personal level, I was looking for a place where I could play more of a leadership role in directing a molecular laboratory and play a larger role in the decision making of assay development. At other institutions I wouldn’t likely have the chance to work with the highest caliber physicians and be able to affect as large a patient population. I felt like this was the perfect spot for me.
Are you drawn more towards academic or clinical medicine?
The great thing about my job is that I can do both! On the clinical side, any assay that I’m evaluating or any patient report that I sign out directly impacts the care and the treatment decisions that an individual patient receives. That’s very rewarding. The academic aspect is rewarding in a different way, being able to work on projects that will meaningfully impact many future patients simultaneous. Also the scientific discovery is important and fun!
Tell me about the technology you use, and how you see it evolving to better advance science and improve patient outcomes?
In the clinical genomics laboratory our two main panels, or tests, are Oncomine and EXaCT-1. They are both next-generation sequencing panels. The Oncomine panel targets 140 different genes, both at the DNA and the RNA level, looking at the most clinically relevant genes—the ones that affect patient care today. That’s our real workhorse test, benefiting about 30 patients a week right now, and about 1,000 patients last year. EXaCT-1 is our whole exome sequencing test that looks at all of the genes in the genome and is a much broader comprehensive test. We have a few EXaCT-1 cases a week.
We also have several new assays that are in development and coming online in the near future. The one we’re most excited about is the TSO-500, which stands for True Sight Oncology, and it looks at 500 genes at the DNA level that are most are clinically relevant. There are some genes that are missed by Oncomine, as well as some investigational genes. In addition, it also covers about 50 genes at the RNA level to look for oncogenic fusions that could make a patient eligible for targeted therapy.
Another test that were working on is a methylation assay. DNA methylation is an epigenetic way of turning-on or turning-off genes. Different tumor types have different methylation profiles, and the methylation of certain genes can make a tumor behave differently. This technology will allow us to look at over 800,000 different methylation sites in a tumor, and it sort of provides a fingerprint for that tumor.
Even further down the road, we look at some of the exciting things that are going on in basic and translational research laboratories and we brainstorm how they can be brought into the clinical laboratory. That’s one of the most exciting aspects of my job and why I wanted to work here, to be able to guide the development of future assays in the lab. For example, the fields of proteomics, metabolomics, epigenetics, etc. are very exciting and could affect how we test tumors in the next 5-10 years.
How would you characterize the work being done here compared to other similar institutions?
That’s a good question. One thing we’re doing very well is looking further into the future than other institutions. A lot of places assess what they need to do now to stay current and provide tests that oncologists are looking for now. But I think we do a very good job of anticipating what we will need much further toward the horizon: how can we push the field of assay development, for example, to revolutionize therapy rather than just meet the current standard.
What do you wish that patients knew about clinical genomics?
Also a great question! Many patients, and sometimes clinicians too, believe that if we sequence a tumor and learn mutations are present, then there will be a targeted treatment option available. Unfortunately, in a majority of cases, there’s not too much else available other than conventional chemotherapy, and the standard of care may be the same as it was decades ago. But we are learning a lot very quickly. Immunotherapy that harnesses the body’s own natural immune system to fight off the cancer is being increasingly used, and there are tons of drugs in clinical trials for certain molecular targets.
The other thing I want people to know about clinical genomics — and this gets me on my soapbox — is about direct-to-consumer testing. Basically, there are a lot of genetic tests being marketed directly to patients. These tests are very easy to get and they claim that they will tell you everything from your ethnic background to susceptibility to colon and breast cancer. But in reality, these tests may only look at a few of the relevant genes and don’t provide the full picture. Some of their reports may suggest that the customer doesn’t have any of colon or breast cancer susceptibility genes, but these tests are not as rigorous or as complete as those we would run for a patient here in the hospital or send to a laboratory that specializes in genetic testing. And it’s very important to interpret any results in the overall clinical context with the guidance of a genetic counselor.
You recently published on NTRK Fusions, can you tell me about your interest in this field?
I’m increasingly interested in how to detect certain cancer-causing alterations that may not be discovered through routine methods. We’re finding that many tumors may have drivers that are not detected through conventional DNA sequencing. NTRK fusions are an important example of these. They were originally discovered many years ago and are very characteristic of two rare tumor types. But more recently, they were found to be prevalent at a very low frequency in basically any tumor type throughout the body. For example, they are seen in 0.3% of colon cancer and 2% of thyroid cancers. They would not be detected by traditional DNA sequencing. So we looked at a few different ways of detecting them: DNA sequencing, RNA sequencing, and immunohistochemistry, and compared benefits and drawbacks of each.
More generally, there is a lot of information that we don’t get from just looking at DNA. There’s information at the epigenetic level, the RNA level, and the protein level, that we are still learning about to understand the whole tumor phenotype. There’s a lot of exciting research occurring, but in the clinical laboratory, we need to figure out what is important to test for.
I always think about analytical sensitivity, clinical sensitivity, and clinical utility. Analytical sensitivity is whether we can detect something in the laboratory. Clinical sensitivity asks the question: If I can detect something, can I then use that information to separate patients? Can I separate patients into different categories? And is there some clinical difference in those patients, some reason, whether that is prognostic information or eligibility for treatments? And then finally clinical utility, which is hardest to prove answers the question, should we even be running this test? If we run this test on this patient, does the information that it gives me benefit that patient? For a lot of the work we do, the clinical utility has already been proven. Patient’s with lung cancer with EGFR mutations or patients with NTRK fusions get very effective targeted therapy. The tests provide actionable information. However, a lot of the testing that is currently in development may not have clinical utility right now, but we’re hopeful that it will in the future.
Where do you see yourself in 5-10 years, what would you like to accomplish professionally?
It is a very exciting time in molecular pathology and I expect a lot to happen in the next 5-10 years! One thing that I’m certain of is that we are going to see a lot higher volume in the molecular laboratory, and I think we are well-positioned to handle it. In addition, I expect our test menu will expand a lot. Some of the assays I’ve touched on, but I’m sure 5 years from now, there will be tests that are standard of care that are not currently on our radar.
In addition, more broadly, new data suggest that a lot of patients actually have germline genetic variants that may affect their cancer susceptibility. We are learning a lot about this now that underlying genetic variance increases chance of cancer in the future. Right now, widespread screening is not standard of care, but I think that is something that will develop, and we should participate. That’s one of our longer-term goals.
In addition, as I mentioned, I’m very interested in developing assays that look at more than DNA point mutations. I think there’s a lot going on in cancer that we’re not currently routinely testing for, and such findings could have clinical utility.
What do you love about your job?
The most rewarding part is signing-out the clinical reports! We do the best we can to get high-quality reports to the patients and their clinicians as fast as possible, so that they can start appropriate therapy. That is the most rewarding aspect of the job, knowing that the tests that we are running are helping individual patients. We get some 30 cases a week, and each is always different and
exciting, and doing a great job for our patients is very rewarding. That said, the clinical assay development and research projects that I’m currently working on are very rewarding as well because they have the potential to benefit patients in the future.
What do you like to do when you’re not working?
We have a new baby, five-month old James, and for now that pretty much takes most of my time when I’m not working. Before the baby arrived, my wife and I liked to explore the city and great food that New York has to offer. But now we have some other priorities and we are enjoying our family life together.
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