University of Arizona Cancer Center researchers are working on a variety of cancer projects thanks to funding from the American Cancer Society.
The American Cancer Society Institutional Research Grant program at the UA Cancer Center, led by Marty Pagel, PhD, supports the development of new investigators to conduct independent cancer research. The ACS-IRG has been competitively renewed at the UA Cancer Center for the past 36 years, and awardees have gone on to garner nearly $10 million in external grant funding in just the last six years to further their research efforts.
A review committee of UA faculty chooses the grant recipients. In 2013, five junior investigators will share $120,000, supporting investigations in the topics of breast cancer and lymphoma and kinase inhibitors. A special interest award will fund an Arizona tribal youth cancer risk assessment project. The researchers and their projects are:
Pavani Chalasani, MD, MPH, Assistant Professor of Medicine, “Retrospective correlation of breast tumor BRCA1 protein expression with response attained after neoadjuvant DNA damaging chemotherapy”
Formerly, most patients with primary breast tumor size of less than 1 centimeter received chemotherapy after surgery. For the majority of breast cancers who have estrogen receptor (ER) positive disease, it is now possible to determine who does not require chemotherapy through the use of a commercially available test called 21-gene recurrence score (Oncotype DX). From this, a score is derived and reported, and helps us determine if the patient benefits from chemotherapy in addition to anti-estrogen therapy. This has significantly changed management of breast cancer, with about 75% of patients being spared the side-effects of unnecessary chemotherapy. Unfortunately, for women with high scores on the recurrence score assay, hormone receptor negative breast cancers, or with multiple positive nodes, chemotherapy is still necessary. It is also usually an essential part of treatment for patients who has relapsed breast cancer (stage 4). What we lack at present is a way to select the type of chemotherapy which is most likely to benefit that patient (predictive marker). There is now evidence suggesting that DNA damaging drugs might be more effective against cancer cells which have defective DNA repair. Detecting this DNA repair is being explored by various techniques, none of which are standardized. We propose to evaluate this complicated DNA repair pathway by determining expression of a key front player, BRCA1.
Hong-yu Li, PhD, Associate Professor of Pharmacy, “VEGFR-2 kinase-selectivity optimization of RET kinase inhibitors”
The proposed work aims to develop a drug that can stop a gene (called RET, RE-arranged during Transfection) that is important in the ability for medullar thyroid cancer (MTC) to grow without affecting other genes. A drug that is targeted to stop RET could improve efficacy and safety as novel therapies for MTC.
Jonathan Schatz, MD, Assistant Professor of Medicine, "Defining a role for Pan-PIM kinase inhibition in non-Hodgkin lymphoma"
Lymphomas are cancers that grow from cells of the immune system called lymphocytes. There are many different kinds of lymphoma and even within each kind there can be many different genetic changes that cause the cells to become cancerous. This project uses an experimental drug called LGH447 that targets a specific mechanism in cells that causes them to grow. The target of the drug, called PIM kinase, is commonly turned on in lymphoma, but we don’t yet know in which kind of lymphoma the drug might work best. Before a new cancer drug can be tested in people, it’s important to figure out how it works and in which kind of cancer it might work best. There are often particular things we can identify about patients’ tumors, called biomarkers, which help us identify patients where a drug is likely to work. This project will use cancer cell lines that came from patients with a variety of different kinds of lymphoma to identify which disease types might respond best to LGH447. Molecular analyses and other techniques will help identify particular biomarkers that go along with sensitivity to the drug. These results will help us bring forward the drug for testing in patients.
Yi Zeng, MD, PhD, Assistant Professor of Pediatrics, "Targeting p21 activated kinases for lymphoma"
There has been significant progress in the treatment of children with lymphoma. Despite improvements in survival, acute and long-term side effects from chemotherapy and radiation remain a problem. My project will explore the role of Paks, a group of molecules inside the cells that control important cell functions, in lymphoma development. I propose to generate novel genetically engineered mouse models to examine if turning down Paks will prevent lymphoma occurrence in these mice. My project will improve our understanding of the causes of lymphoma and help to develop new, effective and safer targeted therapies against this cancer.
Francine Gachupin, PhD, MPH, Assistant Professor of Medicine, "Arizona tribal youth cancer risk assessment project"
We all engage in behaviors that may not always be healthy for us. If these behaviors happen only once in a while they do not harm us as much. If, however, we do not change the bad behaviors and we keep doing them, they can hurt us as we grow older. For example, smoking is bad for us. If we do not stop smoking, our health may be impacted and put us at increased risk to get sick. If students are taught about how to live healthy lives when they are young, we hope they will grow up to be healthy adults and in turn, teach their kids how to be healthy. There is a survey that is done in high schools every couple of years and students are asked about good and bad behaviors. We are hoping to analyze this information for American Indians in the state of Arizona and work with schools and tribes to address what we find. There are questions on the survey that relate to good behaviors to prevent cancers such as lung cancer, breast cancer, cervical cancer and colorectal cancer and these behaviors have to do with not smoking, eating fruits and vegetables, exercising regularly and maintaining healthy weight.
-June 17, 2013