Research Highlights - Archives FY13
Seed Funding Research Program Grant Awards
We congratulate the four investigators who received awards this round.
The seventh round of Duncan Family Institute Seed Funding Research Program awards have been completed. These awards will provide funding at $50,000 per year for two years for a total of $100,000 to support research in the broad topic of cancer prevention and risk assessment in order to allow faculty to obtain preliminary data to improve competitiveness of cancer prevention and risk assessment research grant proposals submitted to external agencies.
Targeting LMW-E/Cdk2 pathway for the prevention of breast cancer
Triple negative breast cancer patients have limited treatment options outside of non-specific standard chemotherapy. Recent studies from our laboratory establish that short forms of cyclin E are over-expressed in 70% of all triple negative breast cancer and that mice expressing those forms are completely protected against breast cancer when Cdk2 is not expressed. Seliciclib and dinaciclib are potent inhibitors of Cdk2 and we would like to test in this proposal if these drugs can prevent breast cancer in our mouse model. Furthermore, we will identify the genes whose expression will be modulated by the two Cdk inhibitors treatment in vivo using gene expression microarrays and biomarker analysis. The results of this study should provide the preclinical rationale for the development of cyclin-dependent kinase inhibitors for the prevention of human triple negative breast cancer especially those with LMW-E overexpression.
The role of LONGf, a novel long non-coding RNA encompassing the risk SNP rs6983267, in colorectal cancer predisposition
Colorectal cancer (CRC) predisposition is not fully understood, as the majority of patients with familial CRC that cannot be included in the Mendelian syndromes do not have a known genetic etiology. The proposed study on the involvement of a gene that did not codify for a protein and therefore named a non-coding RNA in CRC predisposition is innovative as CCAT2 (Colorectal Cancer Associate Transcript 2), could be the “long searched” elusive factor in CRC predisposition. This is located over the genetic variant rs6983267, a single nucleotide polymorphism (SNP) on chromosome 8q24 located outside any coding genes. The central hypothesis of this proposal is that CCAT2 could be involved in the CRC predisposition and increase the risk for CRC in the individuals with risk variant (G) of rs6983267. In this application we will identify the clinical significance of CCAT2 in CRC predisposition by using a large cohort of RNA samples from the Familial Cancer Registry, and will demonstrate the CCAT2 involvement in CRC predisposition using a transgenic mouse model. The identification of the roles of CCAT2 in the predisposition to CRC will not only offer new insights into the molecular mechanisms and signal transduction pathways altered in CRCs but will also be of great clinical significance in identifying new diagnostic molecular markers of colorectal cancer risk and offering potential target for prevention.
Using UV induced epidermal mosaicism to predict skin cancer risk
The vast majority of skin cancers, which affects millions of individuals annually, can be attributed to excessive, but preventable, UV radiation exposure. While population-based screening for skin cancer is effective at reducing skin cancer mortality, it is impractical and expensive. In our study, we propose a DNA-based method to identify individuals most at risk for developing skin cancer. Using chronic UV exposed human skin tissue and mouse models will characterize the effect of UV exposure on genetic mosaicism, the existence of heterogeneous mixtures of cells, which will serve as a marker for risk, and which may ultimately be used to identify individuals most in need of high surveillance.
Discovering new targets for chemoprevention in familial adenomatous polyposis
Familial Adenomatous Polyposis (FAP) is a genetic condition that is diagnosed when a person develops more than 100 premalignant polyps in the colon and rectum. The average age for polyps to develop in patients diagnosed with FAP is in the mid-teens and more than 95% will have multiple polyps by age 35. If FAP is not recognized and preventive measures are taken, there is almost 100% chance for this patient population to develop colorectal cancer. In addition, the study of polyps in FAP offers a model to understand the transition from normal colonic epithelium into premalignant stages and later colon cancer development in populations at average risk. Therefore, our proposed studies to identify important genetic alterations that result in polyp formation in FAP represents an opportunity to identify new preventive measures not only for patients and families with this condition but also open an opportunity to be translated to the general population.
Cancer Survivorship Research Seed Grant Awards
BK Virus Infection in Hematopoetic Stem Cell Transplant Survivors and Renal Outcomes
BK virus is a non-enveloped, encapsulated DNA virus that belongs to the Papovaviridae family. It has been increasingly being recognized as an important outcome predictor when the cellular immune system is impaired, particularly after renal and hemopoietic stem-cell transplantation (HSCT). It occurs in up to 70% of hematopoietic stem cell transplant (SCT) survivors and is associated with prolonged hospitalization leading to severe hematuria in 8-27%. In this study, we will retrospectively review the Stem cell transplant survivors at MDACC to prove the hypothesis that BK virus infection is a marker of poor renal outcomes and overall poor patient prognosis in the SCT survivor population. By focusing on BK virus infection in the HSCT survivor population and its renal and overall survival outcome would help formulate better screening and prevention protocols.
Does Radical Therapy result in Substantial Long Term (>2yrs) Sexual and Urinary Functional Decline compared to Active Surveillance in Men Diagnosed with Prostate Cancer?
Good clinical care of patients with prostate cancer includes careful and standardized assessment of functional and oncologic outcomes. Current research practice for survivorship outcomes in patients with prostate cancer lacks standardization. The well-known side effects after the surgical treatment of prostate cancer that can affect a survivor’s quality of life are erectile dysfunction and urinary incontinence. The long term social and psychological impact and the realization that many prostate cancers have minimal lethal potential, have led to active surveillance programs for low/intermediate risk disease. This too has the potential for significant psychological, physical and possibly oncologic sequelae. The primary goal of this study is to compare long term (>3yrs) sexual and urinary functional outcomes in patients with and without radical therapy for low/intermediate risk disease. Measurements will be made using a web based, validated, standardized, patient- reported quality of life questionnaire. This will allow for us to determine if long term functional outcomes after surgery are durable and whether they differ from the natural decline in function as a result of aging. This will aid in the counseling and long term care of patients with prostate cancer.
Seed Funding Research Program Grant Awards
Targeting STAT3 for the Prevention of ER-negative Breast Cancer
Prevention of ER-negative breast cancer constitutes a clinical obstacle that greatly impedes the effort to reduce breast cancer incidence and mortality. In fact, all ER-negative breast cancers and a significant portion of ER-positive breast cancers are not preventable using currently available preventive drugs. This research chooses the STAT3 transcription factor as a new cancer prevention target based on the preliminary studies that STAT3 is activated in pre-cancer breast cells and mammary glands. We propose to use newly created, orally active inhibitors to suppress STAT3 activation in transgenic mouse models that develop ER-negative mammary tumors highly representing human breast cancers. Thus, this project has significant potential to lead to a reduction in breast cancer incidence and/or mortality within next decade. Successfully carried out, this project may bring 1-2 potent, well-characterized, highly optimized, orally active STAT3 inhibitors into advanced preclinical development as a new class of preventive agents for prevention of many types of human cancer including ER-positive and ER-negative breast cancers.
Prevention of ER Negative Breast Cancer by Targeting P70S6K
Breast cancer is one of the most common women’s cancers in the US and one in eight women develops breast cancer during their lifetime. The most effective way to reduce breast cancer mortality is prevention of early disease; therefore, it is very important to develop early detection and intervention strategies. Tamoxifen (Tam) has been successfully used in the prevention of estrogen receptor (ER) positive breast cancers. However, no agents could effectively prevent ER negative (ER-) breast cancer. We have identified key molecular alterations in ER- breast lesions and will test whether we could effectively prevent ER- breast cancer by targeting these alterations using specific targeting agents. If successful, our findings can be translated to the clinic to prevent ER- breast cancer in high risk women.
Cancer Survivorship Research Seed Grant Award - Older Cancer Survivors
Who will take care of gynecologic cancer survivors: You can't always get what you want
This study focuses on the health care needs and expectations of gynecologic cancer survivors. As the number of cancer survivors continues to grow, it is critical to identify physicians who will take care of these patients after the surveillance period. In this mixed methods (quantitative and qualitative) study, we plan to evaluate the preferences of gynecologic cancer survivors for follow-up care (oncologists vs OB/GYNs) and identify the support and resources OB/GYNs need to broaden access for gynecologic survivorship care in the community. Our study will be among the first to identify barriers and challenges to community-based survivorship care for women with a history of gynecologic cancer and will specifically evaluate age-related barriers to survivorship care from the perspectives of both health care providers and patients. This is an essential first step toward transforming the health care system to accommodate the growing ranks of long-term survivors.
Cancer Prevention and Population Sciences Faculty in the News
- Same cancer, different time zone Paul Scheet, Ph.D.
- End Tobacco: It will take a village to tackle tobacco Ernest Hawk, M.D., M.P.H. and Lewis Foxhall, M.D.
- High-tech 3D mammogram probably saved this woman's life Therese Bevers, M.D.
- Powerful tool combs family genomes to find shared variations causing disease Chad Huff, Ph.D.