Tiffany Taylor (tiffany.taylor06@gmail.com)

Graduate Program:  Biomedical Sciences
Lab PI: Frank Furnari, PhD
Undergraduate Institution: Howard University
Med-into-Grad Clinical training area: Cancer (Hematology/Oncology)
Main clinical mentor:
Santosh Kesari, MD, PhD  skesari@ucsd.edu
Stephen B. HowelI, MD  showell@ucsd.edu
Ida Wong-Sefidan, MD  icwong@ucsd.edu

Quote:   “One research question that I found to be important in the field of neuro-oncology is: What are the key secondary biomarkers associated with progression of glioblastomas? Following biopsy, tissue is often collected to perform genetic testing, revealing biomarkers that are surrogates for the nature of the patient’s disease and allow the patient to qualify for a particular clinical trial. At the time of recurrence, such genetic testing is not repeated. Consequently, second line therapies used may not be effective, simply because the nature of the disease at this stage is not entirely clear. Perhaps, an analysis for secondary biomarkers could provide invaluable information for more efficacious second line therapy options for patients with recurring brain tumors. Currently, I am surveying a ?EGFR-independent genetic signature exclusive to a certain GBM tumor population, which may also be reflected in some GBM patients. After identifying the key genetic players in this tumor population, I may be able to collaborate with Dr. Santosh Kesari’s lab to see if one or more of these genes can be added to the list of possible biomarkers to look for during genetic testing analysis.“

Rational for Med-into-Grad training:
The objective of my proposed research is to elucidate the genetic basis required for primary brain tumors, particularly glioblastomas (GBMs), to overcome therapeutic blockade of the epidermal growth factor receptor (EGFR) and the constitutively active mutant variant, delta EGFR. Specifically, I am investigating the requirement for two apoptosis-related genes: aurora kinase A and clusterin, in delta EGFR-independent tumor maintenance and resistance to EGFR tyrosine kinase inhibitors. The overall long-term goal of my research is to elucidate mechanisms of resistance that can be exploited for the development of more efficacious therapies for GBM patients.

I desired to participate in the Med-Into-Grad program to be exposed first-hand to the pressing issues in the clinical field of neuro-oncology and to gain experience in communicating what I work on with physicians, patients and their families. The clinical aspects of cancer biology had always been appealing to me; thus, I felt that the knowledge and training that I would acquire by participating in this program would be invaluable to refining my thesis project to one that could potentially make a significant translational impact in the field of neuro-oncology. Additionally, the different cancer focus areas of this program would expose me to the range of diagnostic tools and standard medical care that are available to patients afflicted with cancer, and consequently I would gain insight into the current obstacles that are encountered when attempting to treat this disease.

Medical training and identification of medically-relevant research issues: 
During the Winter Quarter of 2012, I was involved in a range of clinical activities including: Hematology-Oncology Inpatient Rounds, Hematology-Oncology Fellow’s Curriculum Lecture Series, Neuro-oncology Outpatient clinic, Medicine Grand Rounds, Lung Tumor Boards, Brain Tumor Boards, and Neuro-oncology Lecture Series. Overall, I would say that through these clinical activities I became aware of the depth of collaborative efforts that go into making crucial medical decisions for patients. I was able to observe the dialogue within the teams of doctors that was required to make the best decision for each patient. More importantly, I admired the physicians’ humility in seeking out the opinions of experts in the fields where they were lacking. Thus, aside from knowing the important research areas to tackle, I believe that the character of the physicians and the opportunity to collaborate on medical cases are invaluable to improving human health.

Nevertheless, one research area that I discovered to be important and am interested in pursuing a career in is cancer genetics. A couple of oncology cases that I was exposed to during my clinical training were linked to genetic mutations. For example, a pair of siblings possessed germline mutations in the E-cadherin gene, which predisposed them to a very aggressive form of familial gastric cancer. I was saddened by the limited treatment options available for these patients and believe that a better understanding of the nature of genetically linked cancers is greatly warranted to provide efficacious therapies and improve overall survival for these patients.

Potential Research collaborations:
Although small cell lung carcinomas are very sensitive to chemotherapy and radiation, the prognosis for this disease is still very poor. This is because a great majority of the cases relapse with Myc driven metastases. Since Myc is a transcription factor, the development of a small molecule inhibitor as a means of targeted therapy is very challenging. Thus, developing a therapy to target this population of tumor cells will be vital to the median survival of patients afflicted with this disease. Perhaps, using antisense oligonucleotides (ASO) to Myc could prove to be an effective therapy. Currently, antisense oligonucleotides against the glycoprotein clusterin are in Phase II clinical trials for the treatment of prostate cancer and non-small cell lung carcinoma. More importantly, antisense oligonucleotides to c-Myc have been investigated in the literature for the treatment of breast cancer. Personally, I do not intend to pursue this as a collaborative project, but I am sure that there are laboratories already working in this area.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:
During my clinical training, I would say that I acquired a solid understanding in both diagnostics and therapeutics used in the field of neuro-oncology. Current diagnostic tools that are used in neuro-oncology are also used in diagnosing other solid tumors. These tools include imaging (MRI, CT, PET-CT) and biopsying with an accompanying pathology report for staging. Given that I was exposed to a number of different cancer types during the inpatient rounds aspect of my clinical training, I was able to see the overlap in the diagnostic procedures. Of importance, I realized that technical specifications, such as the contrast of the MRI imaging are very important to the diagnosis. Often times, some lesions were not detected if contrast was not applied and so validation using many, different imaging machinery was usually required. In the case of GBM, radiation-induced damage or swelling could be mistaken for tumor recurrence and vice versa because of the limitations in imaging. Often times PET-CT is able to clear up this discrepancy, but if this technology is unavailable in some places, then crucial information will not be considered before a diagnosis is made. Thus, the unmet needs in some areas besides UCSD would be to have the latest technology available to make a thorough diagnosis. Patients who are allergic to iodine are unable to undergo MRI imaging with contrast; thus, there is a need for achieving better imaging for these patients at the MRI level.

In the case of therapeutics, standard care for GBM patients is gross tumor resection followed by radiation and chemotherapy. For most patients, this would entail radiation five times a week for 6 weeks in combination with temozolomide for 42 days. Other patients could receive targeted therapies in place of chemotherapy based on their genetic testing results. There are a range of ongoing and future clinical trials, which seek to use of a number of different therapies, with the most common therapies being 5-FU, Avastin, Tarceva, and Tocagen. Despite these options, the overall median survival for GBM patients unfortunately remains unchanged (12-15 months). Thus, the major problems that remain are (1) our lack of understanding the nature of this disease and (2) our lack of options to overcome tumor heterogeneity.

Diagnostic & Therapeutic collaborations:
One research question that I found to be important in the field of neuro-oncology is: What are the key secondary biomarkers associated with GBM disease progression? Following biopsy, tissue is often collected to perform genetic testing, revealing biomarkers that are surrogates for the nature of the patient’s disease and allow the patient to qualify for a particular clinical trial. At the time of recurrence, such genetic testing is not repeated. Consequently, second line therapies used may not be effective, simply because the nature of the disease at this stage is not entirely clear. Perhaps, an analysis for secondary biomarkers could provide invaluable information for more efficacious second line therapy options for patients with recurring brain tumors. Currently, I am surveying a ?EGFR-independent genetic signature exclusive to a certain GBM tumor population, which may also be reflected in some GBM patients. After identifying the key genetic players in this tumor population, I may be able to collaborate with Dr. Santosh Kesari’s lab to see if one or more of these genes can be added to the list of possible biomarkers to look for during genetic testing analysis.

Long term impact: 
As a researcher, I didn’t appreciate how much time is required to provide the best patient care possible. I had a skewed view of physicians, seeing them as these supermen and women, but now I have greater respect for the work that they do and the sacrifices that they make to improve human health. Additionally, this training has provided me with an experience to draw from when I need motivation to be diligent in my thesis work. In the past, I often lost sight of the big picture and clinical rationale for my project, but now I believe that this experience is a great stimulus to keep me focused.

Student-specific experiences:
During this training, I was introduced to the field of genetic counseling. I had always known that I was passionate about communicating science to non-scientist, but had never discovered the career that would allow me to do this in a fitting manner. I am still very passionate about cancer biology and given that therapeutic options for genetically linked cancers are still lacking, I believe that a career in the cancer genetics area would be a great fit for me. Thus, this training has been instrumental in my career goals.

Advice for new trainees--Autumn preparatory quarter:
The best advice that I would give is to attend as many of the Friday morning Hematology/Oncology Curriculum Lecture Series meetings as you can. At these meetings, you will be introduced to a lot of the medical jargon that relates to the different types of hematology disorders that you will encounter during inpatient rounds. I promise that this will prove to be invaluable to how quickly you will be able to understand the different cases presented to you during the clinical training.

Advice for new trainees—Winter clinical training quarter:
To get the most out of the clinical training, it is important for you to be very proactive. When the time is appropriate you should ask questions about things that you don’t understand. Additionally, be sure that you are flexible in terms of availability, because Inpatient Rounds take place at random times. One thing that I would do differently is to additionally attend Inpatient Rounds during the morning with just the Fellow. This allows you to observe the patient interview process and already be knowledgeable of the cases before afternoon Inpatient rounds with the Attending Physician.

Take home perspective on Med-into-Grad at UCSD: 
Overall, Med-into-Grad was an amazing experience. I was able to personally witness the obstacles that oncologists and their patients face each day, which was very humbling for me. I would definitely do it all over again if given the opportunity, because you can always use “a day in the clinic” as a constant reminder of the big picture for your research. I would highly recommend participation in this program by anyone who is involved in translational research.