SDSU/UCSD Partnership: Supported Research

2012 Grant Cycle Under Review 

TUMOR GROWTH, INVASION AND METASTASIS

IDENTIFYING DISPARITIES AMONG CANCER PATIENTS SEEKING FERTILITY PRESERVATION 

Elizabeth Klonoff, Ph.D.
Professor
Dept. of Psychology     

KNOWLEDGE AND BELIEFS ABOUT CANCER GENETICS
AMONG LATINO FAMILIES LIVING IN SAN YSIDRO 

Abstract
Genetics and family history are an important part of understanding someone’s risk of getting some types of cancer.  Most research on cancer genetics has been carried out in academic settings rather than in community settings.  Our goal is to establish a collaboration between the San Ysidro community (served by the Casa Familiar agency) and researchers at UCSD and SDSU.  We will develop this new collaboration in order to understand what the community’s needs are on this topic (for example, resources or educational materials about how to collect one’s family history), and how we can work together to develop a research project that has the goal of improving health in the community.

Full Projects

Evaluation of Novel Sansalvamide A Derivatives as Potential Anti-cancer Agents

Abstract
The sansalvamide A (San A) scaffold is a promising structure for the development of novel cancer therapeutics. We have used the San A scaffold to produce seven compounds that are cytotoxic to pancreatic and colon cancer cell lines at nanomolar concentrations. The San A derivatives are of particular interest because they do not share structural homology with other classes of marketed cancer therapeutics, they appear to inhibit an established target (Hsp90) at a novel site, and they are significantly more potent than the drugs currently available for the treatment of colon and pancreatic cancer.  Known Hsp90 inhibitors interact with the N-terminal domain whereas our compounds are unique in that they target the C-terminal domain and block the binding of inositol hexakisphosphate kinase 2 (IP6K2). It is the overall goal of this project to develop a novel chemotherapeutic agent based on the San A scaffold. It is our hypothesis that analogs of San A with even greater potency and selectively can be synthesized by modifying key structural features identified in our preliminary studies. The specific aims are to: (a) conduct structure-activity studies of San A derivates and select a lead candidate compound; (b) identify the key cellular targets and determine the mechanism by which San A analog kills tumor cells; and (c) determine the efficacy and toxicity of a lead San A derivative in colon and pancreatic xenograft models.

Genomic Instability, Race, and Immune Relationships in Colorectal Cancer

Abstract
Colorectal cancer is common in the U.S., with 153,760 persons acquiring the disease in 2007, along with 52,180 deaths. A key risk factor for colorectal cancer development includes race and ethnicity, with blacks having the highest incidence and death rates for colorectal cancer among groups in the U.S. It is not clear what the cause of this disparity is.  In preliminary data from a pilot study, we demonstrate in a population-based cohort consisting of 503 patients (45% black) that one form of genomic instability driving the formation of colorectal cancers, microsatellite instability (MSI), which generally confers an improved prognosis for survival among patients with colorectal cancer, is half as prevalent among black colon cancer patients compared to white patients. In analysis of a portion of this cohort, tumors demonstrating MSI are strongly associated with CD8+ T cells infiltrating the tumor, and surprisingly, female colorectal cancer patients regardless of race had higher numbers of T cells in their tumors. We hypothesize that colorectal tumors from black patients are more likely to showw less favorable prognosticators towards survival, including a low prevalence on MSI, less CD8+ Tcell infiltrates, and less target gene mutations that occur in the presence of MSI than whites. To explore these findings further, we aim to: (1) determine the prevalence of MSI between black and white patients in a 1,000-person, popuylation-based rectal cancer cohort with survival data, and if this is linked ot a poorer survival among blacks; (2) determine the prevalence of target gene mutations associated with MSI and which infers a better survival prognosis, between blacks and whites; (3) determine the identity and function of the immune cells in MSI colon cancer; and (4) determine if CD8+ T cell infiltration correlated with MSI, race, and/pr gender in rectal cancers.This proposal utilizes over 1500 colon and rectal tumors, with nearly a third from black patients, to address biological and pathogenetic differences between racnes,a nd attempts to identify for the first time the specific immune cells that confer protection from metastasis in MSI tumors.