Author: Kathleen Gray, PhD
This is an exciting time to be working in the field of cancer research. Throughout the last few years, amazing strides have been made toward the ultimate goal: to turn cancer into a chronic disease, that with the right treatment, doesn’t have to be a grim diagnosis. As we recognize World Cancer Day on February 4, I think that is definitely something to celebrate.
Scientists across the biopharma community are making tremendous progress in the way we diagnose and treat cancer, particularly via the incorporation of personalized or “precision” medicine. The goal of precision medicine is to individualize treatments by tailoring them to the biological characteristics of the patient and his or her disease. In my opinion, nowhere have we seen more success in these endeavors than in oncology. Patients with breast, lung and colorectal cancers, as well as melanomas and leukemias, now regularly undergo molecular testing as part of their care process – a key precision medicine diagnostic tool. This gives physicians the insight they need to select the best treatments for their patients to improve their chances of survival while reducing their exposure to adverse effects. At the heart of precision medicine is the concept of applying targeted therapies based on the results of a specific diagnostic test has been realized and put into practice with some remarkable results. A most notable example of this is crizotinib, a drug approved for treatment of advanced non-small cell lung cancer (NSCLC) testing positive for the ALK rearrangement. Not only has crizotinib has become standard of care in the US and EU for this molecular subset of NSCLC patients, it has become the poster child for precision medicine and the power of a “companion” diagnostic test- in this case, a test detecting the ALK rearrangement. The drug-diagnostic approval took only four years from the discovery of ALK rearrangements, a dramatically shortened timeline due in large part to ability to select patients likely to respond to crizotinib (ALK-positive) and spare patients that would not. This drug has opened the door for numerous other studies evaluating other genetic mutations and continues to extend lives of patients with NSCLC today. Take the 2013 phase III trial for example, that showed that crizotinib (Xalkori®) substantially extended the amount of time that trial participants lived without their disease getting worse. Crizotinib was an incredibly exciting development in the field of targeted therapies and ushered in a new era of treatment options for patients with advanced non-small cell lung cancer (NSCLC), a diagnosis previously associated with few treatment options and limited survival two years past diagnosis. Based on the results of the above study, some NSCLC patients can expect to live five-to-ten years or more upon receiving this targeted therapy.
We’ve seen numerous other advances in targeted cancer therapies that block the growth and spread of cancer by interfering with molecular targets involved in the growth of a tumor. Imatinib and nilotinib, for example, are targeted therapies that go after the BCR-ABL protein, which is critical to the growth of chronic myelogenous leukemia cells; and trastuzumab targets the cell signaling protein HER2, which is overactive in about 25 percent of breast cancers.
These breakthrough treatments have already had a game-changing impact on the oncology treatment community, and many more are currently under development.
Fighting back with immunotherapy
Though, I think, some of the most exciting results are emerging in the field of immunotherapy, where treatments are being developed to make the patient’s immune system attack cancerous cells in real time. The last several years have seen the approval of several monoclonal antibody (mAb) therapies known as “checkpoint inhibitors” – named because the proteins these antibodies target serve as negative regulators to keep the immune system in-check and avoid the ramifications of an over-active immune response. However, in the context of tumors, these proteins blunt the immune response to cancer cells as well. Checkpoint inhibitors, such as ipilimumab, pembrolizumab, and nivolumab have fundamentally changed the treatment of advanced melanoma and now advanced NSCLC as well, and most experts believe this is only the beginning of how immunotherapies will revolutionize cancer treatment. And unlike many targeted cancer drugs, checkpoint inhibitors appear to be helpful against many different types of cancer, making them especially valuable in the fight against cancer.
Another advancement in the immunotherapy space is the development of Chimeric Antigen Receptor T-Cell Therapy (CAR T), in which the patient’s immune cells are engineered to recognize and attack their tumors. In these cases, the T cells are genetically engineered to produce chimeric antigen receptors that can recognize a specific antigen on tumor cells when they are infused back into the patient. Once back in the patient’s body, the goal is for those altered T cells to multiply and kill the cancer cells that harbor the antigen on their surfaces. This research is still new, but early results have shown extraordinary results, including a 2013 study from Memorial Sloan Kettering Cancer Center and the National Cancer Institute that reported complete remission rates in 23 pediatric and 17 adult patients with relapsed/refractory acute lymphoblastic leukemia, using CAR T cells. Industry experts hope it is only a matter of time before this therapy becomes a mainstream tool for oncologists and an accessible option for all patients.
All of this research holds incredible promise, though we still face many roadblocks. Many of these treatments are designed to meet the unique needs of individual patients, which makes testing these drugs in a clinical setting, and finding “biomarkers” to inform treatment a lot more complicated. Identifying the variables that separate patient populations, then recruiting the targeted group into trials is a complicated process that adds time, cost and risk of failure to the clinical trial lifecycle. These trials face many of the same challenges rare and orphan disease researchers deal with – the patient population is so small and dispersed that it is nearly impossible to recruit enough participants to a single trial site to gather meaningful results. As we go forward with this research, we need to improve our methods for finding patients, and take advantage of the data we collect to make the most of their participation in these trials while minimizing the disruption to their lives. Innovative tools like liquid biopsies, which detect circulating tumor cells (CTCs) and cell-free DNA in blood, for example, can minimize invasive procedures to more proactively, and less painfully, monitor the patients’ resistance to a treatment before the tumor starts growing. Liquid biopsies are still new but could soon be a normal part of the clinical practice, giving physicians and patients more convenient tools to actively monitor their cancer status.
As we celebrate World Cancer Day, it is important to note that none of these innovations could have been achieved without tremendous collaboration across the oncology research field. We have seen competing companies working together and joining forces with academia and government to break down silos and invest millions of dollars in delivering these innovations. In addition, courageous and informed patients are actively involved in their own cancer treatment, engaging with their physicians and the oncology community like never before to provide the most invaluable contribution of all toward bringing life-saving therapies to others- participation in clinical trials. Together we are making tremendous strides, and together we will continue to fight this battle to improve human health and hopefully save millions of lives in the process.
Kathleen Gray, PhD is a guest blogger who previously worked with Q2 Solutions.