Emerging life sciences series: Q&A with the Editor

Tell us about your earlier research experiences. What drew you to the intersection of cancer and neuroscience research? After my first year of clinical residency in otolaryngology, I joined the lab of Dr. Ziv Gil. His lab was studying pancreatic cancer, one of the deadliest cancers. Interestingly, the lab was focused on the intersection between immune cells, nerves, and cancer cells. Pancreatic cancer, like other exocrine gland tumors (for example, prostate and salivary gland tumors), is highly innervated and has a unique feature: the ability to invade and disseminate along nerves. This feature, called perineural invasion, is an ominous sign and is actually the fourth route of metastasis, along with local invasion, lymphatic spread, and hematogenous spread. In perineural invasion, tumor cells use the nerves in the vicinity of the tumor as “highways” for distant spread. In patients, perineural invasion can cause pain and paralysis. Unfortunately, these “highways” often lead to critical structures such as the spine and brain, which limits our ability as surgeons to completely remove the tumors. Can you tell us about some key scientific developments that led to your current thinking about the tumor microenvironment, immune response and health outcomes? Throughout my training and as a junior faculty member, I was always amazed by the minimal (if any) role attributed to the nervous system in cancer. As a clinician, we consider nerves mainly in the context of pain, or we think about how invading tumors or cancer treatments damage nerves. However, considering that the nervous system controls every aspect of our life, in health and disease, it was peculiar that the role of nerves in regulating cancer growth, progression, and response to therapy was neglected for many years. The article that marked the change in the field, published by Claire Magnon et al. in Science in 2013,[1] showed for the first time that there is an orchestrated interaction between the autonomous nervous system and cancer development. This article left a strong impression on my mission as a scientist and led me to think about a fundamental question: how do nerves get to the tumor microenvironment? I realized that the process may be similar to angiogenesis in that a cascade of signals coming from cancer cells and maybe other cells in the tumor microenvironment might be involved. This led me to study paracrine signaling, but this time I was looking in the opposite direction from my view as a clinician—that is, at how cancer cells and nerves interact. During my Ph.D. studies, I obtained experience in dissecting paracrine signals, including vesicle-mediated signaling, that led to our findings about the ability of cancer to “hack” the nervous system. In your view, what are the pressing and longer-term questions at the interface of cancer and neuroscience and how should they be prioritized? What do you see as the major challenges in cancer neuroscience research, and future directions to overcome barriers? The major challenge is the overcoming of disciplinary barriers to conversations and collaboration between scientists in each field. There are many technical obstacles (for instance, cancer biologists usually do not understand neuron culture, andmany neuroscientists are not familiar with cancer models), but these challenges can be easily sorted out through discussions and data sharing. I had dual training, but it is not a necessity if you have good collaborators. How is cancer neuroscience a great example of opportunities for early-stage investigators to engage in interdisciplinary research? Engaging in interdisciplinary research is the essence of advancing the field of cancer neuroscience. Getting trained in both fields and becoming an expert in both is nearly impossible. I was fortunate to have great mentors who became my collaborators after my transition to independence. My mentors have expertise in fields that would have taken me a lifetime to acquire, including Dr. Jeffrey Myers in cancer modeling and P53 biology; Dr. George Calin in RNA biology; and Dr. Patrick Dougherty in neurobiology. Each of these mentors has dedicated his life to a specific topic, and taking advantage of what each one brings to the table has made it possible for all of us to make new discoveries. As the guest editor, what are your goals for the upcoming thematic issue on neuron-tumor interactions and how will you measure success? My goals are threefold: one, to introduce the field of cancer neuroscience to the readership of Advanced Biology and to expose neuroscientists, cancer biologists, and clinicians to the field; two, to foster discussion and collaboration between the disciplines; and three, to drive policymakers and key stakeholders, such as the National Institutes of Health, to invest in cancer neuroscience research since this is an unexplored territory that holds a lot of therapeutic potential for cancer patients and their caregivers. The most important and personally exciting deliverable for me would be to see more clinical trials looking at neuromodulation as cancer therapy. I think that until the first neuromodulatory approach or therapy targeting the nervous system is Food and Drug Administration/European Medicines Agency-approved for cancer, we will not be satisfied. But we are becoming more optimistic by the day. Moran Amit, MD PhD mamit@mdanderson.org Photo Credit: Photograph courtesy of Dr. Moran Amit.