Making Dents in Lung Cancer Discoveries

Mark M. Fuster, M.D., is a pulmonary disease specialist in San Diego and has worked in the field of lung disease for more than 15 years. What started with taking care of patients in a clinical care setting turned into a passion for research, which eventually led Dr. Fuster to receive our LUNG FORCE Lung Cancer Discovery Award. He hopes his research can lead to new strategies to cure cancer through the immune system. We sat down to talk with Dr. Fuster about his work in lung cancer research and how it could impact patients.

How did you become interested in research?

I go back to having interest in lung disease and pulmonary care. During residency, I picked pulmonary and critical care as my area of specialty; and being challenged with lung cancer patients in particular had a significant impact. I also spent some time working in New Zealand where I witnessed the heavy toll of lung cancer on patients that I treated in a respiratory hospital. After some further exposure as an early clinical fellow in training, I was driven to the clinical and research challenge and opportunity, and I began to engage in research to try to make a difference for these patients.

Why lung cancer?

I was struck clinically by the intensity of lung cancer and the high morbidity and mortality of this disease, with an overall prognosis that has remained poor for decades. How quickly this cancer spreads makes it challenging to achieve a cure, even if diagnosed relatively early. I realized that even if we eliminate all cigarette-induced lung cancer, which accounts for most of the disease burden, we're still left with a lot of lung cancer death. It is a scary diagnosis, and remains a major challenge in our society.

How did you get to where you are today?

My early research was mentored by expert biochemists studying the glycosylation, or "sugar-coating" of molecules on the surface of cancer cells, which turns out to play important roles in their ability to spread in the body. We were looking for ways to tinker with those molecules to make it harder for the tumor cells to spread, while also looking for ways to inhibit their growth. That's how I started my cancer research interests. Shortly thereafter, I became interested in the body's response to cancer, which is the focus of my current interest.

What body responses are you studying?

For several years, my lab focused on what causes blood vessels and lymphatic vessels to feed and grow a tumor. We came to understand a variety of interactions between immune cells and these vessels. Interestingly, targeting some of the sugars produced by the cells that line these vessels appears to be important in controlling the movement of immune cells. Some of those immune cells are "bad" (they tell the immune system to leave the tumor alone) while others are "good" (they instruct T cells in the body to kill the tumor). We are learning about the effects of genetically altering the sugars, which alters the speed of immune cell traffic in and around the tumor.

Further, our work has found that the immune cells themselves carry unique sugars on their surface. Changing or inhibiting some of those sugars can potentially improve how the immune system sees cancer as a pathogen or bug, so that the body's T cells can kill the tumor more aggressively and specifically.

Tell us about your current American Lung Association funded study.

My current American Lung Association funded study delves into the functions of dendritic immune cells, which present cancer antigens (or cancer-specific molecules to ideally be sensed as "foreign") to the immune system to instruct anti-cancer responses. Dendritic cells are very important in alerting your immune system to "bad" foreign material or cells (including viruses and even cancer cells) in your body. When working correctly, they tell T cells to hunt and kill the cancer cells. In lung cancer, that process is very inefficient. Molecules from cancer subdue the dendritic cell (and T cell) functions. There are some ways we think targeting sugars can restore anti-cancer functions; including roles in controlling cell movement and growth. This may assist in our ability to design new therapies to help the body recognize and fight cancer. So the heart of this grant is to begin discovering how altering these sugars might improve anti-cancer immunity to kill lung cancer cells in experimental systems.

How can your findings apply to patients?

Where these insights might overlap clinically gets interesting. There's a big immunotherapy revolution going on in lung cancer as well as a number of other cancers. It appears that some antibody therapies can "ramp-up" the general aggression of T cells. This can help in killing cancer cells, but the actions of these therapies are not very specific, and so not all cancers respond (with responses seen in less than a quarter of lung cancers that have spread). The actions of the "ramped-up" T cells can be non-specific, thus leading to auto-immune side effects that can be very serious in some patients. It is appealing to improve both the intensity and specificity of the anti-cancer actions possibly by some of the approaches mentioned above.

How did you first become involved with the American Lung Association?

There have been ongoing opportunities that kept my awareness and ties to the American Lung Association even before this grant. The Lung Association's LUNG FORCE initiative is very important. Every year, I join my local Lung Association in San Diego to do LUNG FORCE Walks for all lung diseases, and lung cancer is at the center-stage for our LUNG FORCE efforts. I enjoy participating in some of the walk events and community action and education activities. These help to rally advocacy for research, anti-tobacco efforts and lung disease awareness.

What motivates you to keep coming to LUNG FORCE Walks—every year?

I hope to grow the link between clinical and research efforts with the real people/patients that are being impacted in positive ways—the patients, their families and the community together. Everyone that's involved has passion to help. It's nice to both contribute and visualize the gains we can make with our community for both the sake of our patients as well as public health and prevention.

What are some common questions you get?

What's new in lung cancer care and what's immediately available? How close are we to new things that can make big impacts? The efforts of many before us along with current efforts by our research community may be making a dent now through new ways to augment immunity, but we have a long way to go.