Boryana Eastman (beastman@ucsd.edu)
Lab PI: Steven Gonias, M.D., Ph.D.
Graduate Program:  Biomedical Sciences
Undergraduate Institution: Wellesley College
Med-into-Grad clinical training area: Oncology
Main clinical mentors:
Lyudmila Bazhenova, M.D.,  (lbazhenova@ucsd.edu)
Paul Fanta, M.D. (pfanta@ucsd.edu)
Frederick Millard, M.D.
Mark Fuster, M.D.
John Adamson, M.D.

Quote: “Med-into-Grad introduced me to the challenges of modern oncology. I learned it is not possible to save every patient and that clinicians have to set reasonable treatment goals concerning patient survival and quality of life. The hardest thing for me was that many of the patients I saw in both the in-patient and out-patient setting had limited time expectancy and many passed away during my training.  I wish that some of the research I do will help patients clinically in the future.”

Rational for Med-into-Grad training: 
Initiation and progression. uPAR is a GPI anchored protein, whose expression is prominent in many human malignancies, but it is virtually absent from most normal tissues. It has been associated with more advanced cancers and worsened prognosis. My thesis research builds upon previous work from our lab and examines the role of uPAR in cancer establishment and survival.

The nature of my research is very basic with a few mouse models. I was interested in Med-into-Grad in order to see how some of these basic research principles were applied in treating patients with the emergence of targeted therapies. I was also interested in seeing different types of cancer, since the focus of our lab is currently breast cancer, but we are looking into the role of uPAR in other types of cancer such as pancreatic.

Medical training and identification of medically-relevant research issues: 
During my training I shadowed physicians during inpatient rounds, as well as during outpatient clinics. I was given the opportunity to talk to both patients and physicians and participate in a number of case conferences focusing on different types of cancers including, but not limited to breast cancer. I learned about different clinical trials in progress as well as some of the most common side effects of cancer therapies. It was fascinating to see how some of the new targeted therapies (including a mesothelin antibody) have dramatic results in shrinking patients’ tumors without many additional side effects. My clinical training demonstrated to me once more how combining therapies and including additional specific therapies benefits patients without decreasing their quality of life. Therefore, although a therapy cannot cure all or on its own eliminate the malignancy, it is still beneficial. Another very important aspect I saw, and something I did not fully realize prior, is how important quality of life is and therapies adding as few side effects as possible will be the best ones to be developed. 
My clinical training strengthened my determination to do research and introduced me to other types of cancer. Although major strides forward have been made in the treatment of breast cancers, other malignancies are still far behind. My specific proposal focuses on investigating the role of uPAR in some of these less treatable cancers.

Potential Research collaborations:  Currently we are not pursuing a collaborative experiment, but I am looking into whether uPAR has a role in other types of cancer in addition to breast cancer, which our lab has studied extensively.  If I obtain promising in vitro data, I will not hesitate to contact my clinical mentors for guidance in translating this data into in vivo experiments. For example our lab is very interested in the role of uPAR in promoting cancer stem cell like properties in breast cancer cells and I will be interested to see if this is true in lung or pancreatic cancer too.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs: Since I saw a variety of different types of cancer I feel I got a good overview of the diagnostics and therapeutics used. The majority of cancer cases I saw were lung, gastro-intestinal, and breast cancers. Most cancers were diagnosed using imaging techniques and pathologist examined biopsies after patients presented with pain, bumps, or abnormal lab results. The biopsies were characterized using a number of cancer specific markers aiming at determining the type of cancer. For example for breast cancer – ER, PR, and HER2 status was studied and based on that different therapeutic strategies were undertaken. For cancers of unknown origin, samples were sometimes sent to outside laboratories looking at different genetic markers in order to establish the tissue of origin and undertake appropriate treatment. Additionally, patients’ cancers were studied for different genetic mutations (such as c-Kit and EGFR mutations) making them unsusceptible to certain targeting therapies. 

Treatment options were dependent on the stage and type of cancer. Most times, surgery was the first line of defense followed by chemotherapy and radiation. Doxorubicin and platinum based drugs were used widely in variety of malignancies. Sometimes, chemotherapy was used before surgery in an attempt to shrink the tumor and improve the chance of success of the surgery. In cases in which specific tumor markers were present, specific therapies were ordered such as an EGFR inhibitor (Gefitinib/Iressa ), Mesothelin antibody (MORab-009), HER2 specific antibody (Trastuzumab/Herceptin). In cases where no specific markers were present or have not yet been identified, no other therapy was prescribed.

There remain a number of major issues in both cancer diagnostics and treatment. Many cancers present with non-specific symptoms such as abdominal pain and are diagnosed when there are in more advanced stages. Once diagnosed, cancers have usually acquired various mutations and are sometimes not responsive or grow unresponsive to multiple treatments. Therefore identifying more specific markers would allow development of more therapies damaging different growth pathways at the same time and in this way killing cancer cells more effectively. This will also reduce the chances of the cancer developing resistance to the treatment. One of the major problems in developing new therapeutics is the varied nature of the cancer and identifying proteins crucial for its survival. Additionally, cancer cells use many essential growth pathways, so disrupting these could lead to undesirable side effects.

Diagnostic & Therapeutic collaborations:  Currently, I am planning on investigating the role of the receptor I study in the laboratory in different types of cancer, such as lung cancer. If I discover any role in promoting lung cancer growth and development, I will be interested in taking these studies in mouse model systems. Additionally, I will be interested in obtaining some biopsy samples and verifying whether uPAR is expressed in specific subtypes of lung cancer and whether its expression is associated with expression of known cancer markers. I am sure that the connections I have established with my clinical mentors would allow me to obtain these and I believe that they together with my thesis advisor would be valuable resources in designing these studies.

Student-specific experiences: Med-into-Grad introduced me to the challenges of modern oncology. I learned it is not possible to save every patient and that clinicians have to set reasonable treatment goals concerning patient survival and quality of life. The hardest thing for me was that many of the patients I saw in both the in-patient and outpatient setting had limited time expectancy and many passed away during my training.  I wish that some of the research I do will help patients clinically in the future.

Advice for new trainees--Autumn preparatory quarter: The class offered by UCSD in the fall quarter was useful as a general introduction to different diseases. However, what I found more useful were the morning talks I attended at the Moores Cancer Center. They focused on different aspects of hematology and oncology and current research focusing on the disease was presented in the context of a patient’s case. It was a great introduction to the clinical treatment in the winter - it helped me understand better the cases I saw and to follow the terminology the clinicians use more easily. 

Advice for new trainees—Winter clinical training quarter:  The physicians are the Moores Cancer Center were very helpful and cordial. They were accommodating and allowed me to shadow them through most of their patient visits. For the inpatient rounds, it was best to contact the Oncology fellow for scheduling and locations and be prompt and patient, since sometimes the clinical faculty run a little late after their morning clinics. For the outpatient rounds, again being prompt is helpful, you might also need to bring some reading, since a lot of documenting is done after each visit and there is some down time. For the case conferences it is best to be early, since sometimes space is an issue. In hindsight, I wish I had contacted the person in charge of coordinating clinical trials, since that would have been something interesting to learn more about.  So I would recommend investing some time and effort in this. .

Take home perspective on Med-into-Grad at UCSD:
I would highly recommend this program to other students. In addition to being a wonderful learning experience, it was also very motivating for my laboratory research. It is important to see how quickly cancer progresses and how the discoveries made in laboratories could one day be improving the quality of life of cancer patients