Gina Mantia-Smaldone, MD, pursues her oncologic goals with a persistence that speaks volumes about the imperative value of her work. The Assistant Professor at Fox Chase Cancer Center, Philadelphia, conducts translational and clinical research in hopes of discovering targeted therapeutics for gynecologic malignancies, specifically ovarian and endometrial cancers. She hopes eventually to be able to "get patients into remission for longer periods of time, improve their quality of life, and even try to find a cure."
A native of Long Island, N.Y., Mantia-Smaldone has followed in the footsteps of her father, a medical internist in whose office she worked as a teenager. "I would tag along when he did rounds and watch how he was with his patients-so caring and giving. It made me want to go into medicine."
She graduated from SUNY Stony Brook School of Medicine, where she met her husband who is a urologic oncologist at Fox Chase. She then completed an OB/GYN residency at Magee-Womens Hospital of the University of Pittsburgh Medical Center. She subsequently completed a postdoctoral fellowship in ovarian cancer immunology at Magee, plus an additional 2 years doing basic science and ovarian cancer research, before completing a gynecologic oncology fellowship at the Hospital of the University of Pennsylvania.
"It was an important time for me," recalled Mantia-Smaldone. "At Magee, I had the opportunity to work in a lab that was focused on immunology and learn a lot about endometrial and ovarian cancers, all triggering a translational component to my future career. When I got to the University of Pennsylvania for a fellowship, I focused on BRCA1-related ovarian cancers and immunology, which would become a common theme in my subsequent work."
Asked why she has stayed on an ovarian cancer track, Mantia-Smaldone said that, while strides have been made in cancer in general and dents have been made in ovarian cancer, in particular, "... there is still so much that we don't know. We can sometimes get cancer patients into remission, but there are still so many patients in whom it will still recur despite our best efforts. We need to look more at the underlying biology of cancer and see if there is a way that we can outsmart cancer. That is where my research is now concentrated."
Exploring Tissue Specimens
While clinically treating patients both surgically and with chemotherapies, Mantia-Smaldone also finds tremendous satisfaction in the lab. "My clinical research leads to the development of clinical trials in ovarian and endometrial cancers. I also do translational research using available tumor specimens to correlate clinical outcomes with biologic markers."
Mantia-Smaldone works both with industrial partners and fellow researchers at Fox Chase to evaluate specimens from ovarian cancer or endometrial cancer patients, and to find potentially new therapy targets.
"I use the Fox Chase biosample repository for my work," she explained. "Patients who come to Fox Chase for surgical procedures donate their tissue and blood samples for research purposes. Those specimens are de-identified, however, specific clinical information-like type of cancer, stage at presentation, treatments received after surgery, how long the patient lived until cancer came back or how long they survived-is retained. The specimens are saved for future research."
Mantia-Smaldone and colleagues look at the tumor gene mutations and protein expression via various techniques, including immunohistochemistry, flow cytometry, PCR analysis, etc.
"Some is done here, while some specimens are sent to companies running these tests routinely to identify up to 1,500 different mutations in the specimens," she detailed. "We then try to correlate the biologic results with the patient's clinical outcomes. Hopefully, that information will translate to a clinical trial during which we can look at new agents that target those tumor mutations."
Mantia-Smaldone has collaborated with James Duncan, PhD, one of the kinome investigators at Fox Chase. "We have one target that looks very promising in ovarian cancer," she told Oncology Times. "We also have a second project under way in which we have a promising target for endometrial cancer. So the next step, after looking at these patient samples, is to evaluate the mutations in a mouse model where we hope to see a response to justify a phase I clinical trial."
Asked if there is a specific expectation for that response, Mantia-Smaldone said hopes and expectations develop organically from observations.
"We evaluate a mouse model to see exactly how a drug would act against the cancer. Once we get promising results in a mouse, we can use that information to develop a phase I clinical trial where we study safety and some efficacy data of the drug in human patients with cancer. Often they are patients with recurrent cancer who may not have any other treatment options. Information from these early clinical trials allows us to expand and study an even larger group of patients. Hopes and expectations for a drug become more fully realized as research continues."
Mantia-Smaldone is also leading a phase I study at Fox Chase in hopes of perfecting a new surgical technique for ovarian cancer.
"The technique involves using laparoscopy and a molecule G that is infused intravenously into the patient," she detailed. "Essentially, it helps to highlight hidden lesions at the time of laparoscopy. It employs a molecule that gets broken down by the tumor cells so that, in a near infrared light at the time of surgery, surgeons can identify lesions better than just by looking at the tumor under normal white light. The hope is that we can help to highlight areas where we may not have seen disease, thereby improving on surgical technique and patient outcomes."
Strength Through Support
The clinician/researcher said she feels very fortunate as she continues along her expanding career path, and credits wonderful mentors as well as tremendous institutional support at Fox Chase for her projects. She also finds continuing support in the face of one Fox Chase colleague in particular, her husband Marc, as well as their young daughter and son.
"Because Marc and I are both involved in medicine, our dinner conversations are very odd at times," she said with a chuckle. "Our common interest in oncology helps us to understand each other's career pressures. There are challenges that we both go through with our patients, especially when they have recurrent disease and don't do well. It's nice to have someone close to you who understands. Really understands. Because we work at the same institution, we see more of each other here in the hospital than we do at home. And to see your significant other in action... that's really kind of great."
Asked what the medical future holds for ovarian cancer, Mantia-Smaldone reflected on "the gynecologic cancer that is generally presented at more advanced stages and inflicts higher rates of recurrence, and unfortunately poorer survival rates, than other cancers. Immunology is a newer player in ovarian cancer," she noted. "We still don't know who are the appropriate candidates for the therapy, or when best to initiate treatment-whether in the initial or refractory treatment. There are some ongoing clinical trials trying to answer those questions right now. Additionally, we have new therapies that recently have been FDA-approved, including PARP inhibitors. I suspect we will need to combine therapies to be able to achieve better clinical outcomes."
While underscoring the probable need to combine therapies, Mantia-Smaldone also stressed the need to combine intellectual capital between various institutions and research efforts.
"Ovarian cancer will not be tamed by just one individual; it's going to require groups of individuals collaborating to push the needle forward. And, ultimately, it will be the patients who help us to learn more about the disease. As more patients participate in clinical research trials, we will gain vital information about how to best treat cancer. In return, patients potentially may gain access to newer drugs that are not yet approved. From a provider perspective, it is our responsibility to make patients aware that there are options besides standard of care that may improve their outcomes. They need to be educated to the fact that when they participate in a study they may receive treatment that improves upon that standard of care."
Looking to the future, Mantia-Smaldone said she hopes to develop her own research interests "on a national level and be more involved in collaborative, multi-institutional group trials geared to improving upon the standard of care." And her reasoning is both simple and sound: "There is a lot of work that I can do in this field to help patients."
Valerie Neff Newitt is a contributing writer.
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