When people talk about curing cancer, an oncologist’s reaction likely is: What kind of cancer? If you answer “breast cancer,” the oncologist will likely want to know which of its many varieties do you mean?
Precision medicine — the customization of treatments targeted to specific patient populations for specific ailments — has been made possible in recent years by advances in technology and the resulting breakthroughs in understanding how a given disease may differ among patients.
Researchers now have much more detailed information about individual patients, thanks to advances in DNA analysis, enabled by technology known as next-generation sequencing. Next-generation sequencing makes it possible to identify more rapidly among all patients with a given disease smaller sub-populations that share common DNA sequences or alterations, and to determine whether these sub-populations may benefit from different treatments.
Steffan Ho, M.D., Ph.D., Vice President and Head of Translational Oncology at Pfizer, is an anatomic pathologist and cancer researcher. “In my role as a pathologist,” he says, “I would help patients with cancer by examining tumor tissue from the patient under a light microscope in order to make a specific diagnosis, which the health care team would then use to develop the patient’s treatment plan. The advances in technology that we have seen recently, including next-generation sequencing, enable us now to go beyond the light microscope to look at the molecular characteristics of the patient’s tumor. We can now identify molecular sub-types of cancer, allowing us to better match the patient to the specific treatment for them."
Historically, Ho relied on what are known as pre-clinical models to develop an understanding of a particular cancer. Increasingly, though, Ho is able to rely on real tissue samples from patients, and liquid biopsies in which a patient’s blood is analyzed for telltale DNA fragments or whole cells that are shed by a tumor into their bloodstream.
Next-generation sequencing also allows researchers to sequence samples that couldn’t before be analyzed, and to sequence not just one DNA alteration at a time, but many. Moreover, it’s becoming possible to read more DNA from more types of tissue samples, giving researchers more clues to help them try to target the right medicine to the right patient.
Sequencing of tumor DNA has also allowed researchers to identify increasingly uncommon subsets of cancers. Take, for example, a subset of patients with a given type of cancer who may benefit from a particular drug. If that subset of patients represents only 1% of all patients with that type of cancer, researchers need a way to identify those uncommon patients.
Next-generation sequencing of a patients’ tumor or blood offers just that — a clinically feasible single test researchers can use to identify those patients. Furthermore, next-generation sequencing can identify not only the 1% of patients with tumors containing a specific DNA alteration who may benefit from one treatment, but also the many other patients, each with tumors that may have other uncommon DNA alterations, who may benefit from other treatments.
But sequencing of DNA is only part of the story. “It provides a critical view of the underlying biology of cancer,” Ho says, “but there are other sources of information from a patient’s tumor that can also help us match the patient to the right medicine for that patient. We also measure the expression of RNA and proteins.” These can also help match the right medicine to the right patient.
Ho says he tells people he talks to outside of clinical research that, from the standpoint of precision medicine and the clinical trial process, the last several years have been remarkable. In previous years, promising drugs often didn’t perform as expected in clinical trials and when they did, the benefit may have been clinically marginal. “That was unsatisfying,” he says of those years. “Everyone doing this job…wants to spend our time working on the drugs that we think have the potential to make a real difference to patients.”
Researchers are also aware that these treatments can help their own loved ones and maybe even benefit the researchers themselves. “Many of us have some sort of relevant experience in our own lives,” Ho says.