The Landon Foundation-AACR INNOVATOR Award for Cancer Prevention Research was established to recognize the outstanding achievement of an early-career assistant professor in the field of cancer prevention, and to provide support for cancer prevention research of significant scientific merit in any discipline across the continuum of research. The goals of the program are to: encourage younger investigators to pursue cancer prevention research of significant scientific merit; provide the support necessary to sustain and enhance highly meritorious cancer prevention research; foster interactions between and among cancer scientists and disseminate the scientific knowledge about cancer prevention research; and contribute to a global impact against cancer.
2012 GRANTEE
Guang Peng, M.D., Ph.D.Assistant Professor, University of Texas MD Anderson Cancer Center, Houston, TX
Targeting the DNA Repair Network as a Novel Approach for Cancer Prevention
"An important way to reduce cancer deaths in the future is to improve cancer prevention. However, a big challenge for effective cancer prevention is to identify chemopreventive agents with demonstrable efficacy and safety. To overcome this challenge, the most promising approach is to develop targeted chemopreventive agents that are based on the genetic alterations in premalignant cells. DNA repair pathways play a critical role in the cellular response to replication stress, a common feature of premalignant cells across multiple types of cancer. Early in the process of tumorigenesis, genetic alterations such as activation of oncogenes and loss of tumor suppressor genes are implicated in inducing replication stress by providing premalignant cells with excessive growth signals. Replication stress results in the higher level of replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair and survive from replication-associated DSBs is homologous recombination (HR). This key link between HR repair and cellular survival responses to replication stress provides us with a mechanistic rationale for exploiting synthetic lethality between HR repair inhibition and replication stress in premalignant cells.
"Our research goal is to identify novel inhibitors of the HR repair pathway that selectively kill premalignant cells by targeting cellular survival responses to replication stress. With the support from this award, we aim to use an innovative, imaging-based, high-throughput HR repair assay to conduct screenings with chemical libraries containing FDA-approved drugs and natural products. We will also use both an in vitro cell culture system and an in vivo xenograft animal model to test the chemopreventive effects of the newly identified chemical inhibitors. The funding support from The Landon Foundation-AACR INNOVATOR Award for Cancer Prevention Research is essential for the success of our research in this very promising direction. We anticipate identifying agents that can convert existing replication lesions into fatal lesions that selectively kill premalignant cells. This preventive strategy has a great potential to be applied to a broad spectrum of cancers with the same characteristic feature, i.e., elevated replication stress."
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2011 GRANTEE
Megan J. Huchko, M.D., M.P.H.Assistant Professor, University of California, San Francisco, San Francisco, CA
Cervical Cancer Screening with a Novel Biomarker in HIV-infected Women
"Cervical cancer has a disproportionate impact on women in developing countries. This has historically been due to socioeconomic disparities and poor health care infrastructure, however, in the last two decades, the HIV epidemic has worked to synergistically increase the biologic and health care factors associated with increased cervical cancer incidence and mortality in these countries. The impact has been most dramatic in sub-Saharan African countries such as Kenya, where cervical cancer is the most common cancer killer among women. Cervical cancer prevention efforts that have reduced the incidence of cervical cancer to close to zero in resource-rich countries are costly and not available in most low-resource countries. Novel testing and treatment strategies that can be carried out in low-resource settings are urgently needed to prevent cervical cancer in these countries, especially among the growing population of HIV-infected women. Protein biomarker detection in the cervix has the potential to increase the accuracy in diagnosis of precancerous cervical lesions. Our research team is in the final phase of a pilot study to test the feasibility and accuracy of a biochemical assay for the protein p16INK4a for screening among HIV-infected women in western Kenya. If the test performance is favorable, a biochemical assay could be developed as of a point-of-care screening test, which would be ideal for a low-resource setting. Our ongoing work is the first study looking at the performance of p16INK4a in HIV-infected women and the first to look at the performance of the biochemical assay in a low-resource setting. The Landon Foundation-AACR Innovator award will allow us to apply our pilot study data in a larger trial to evaluate the clinical performance of p16INK4a among HIV-infected women. This work will advance the field of cervical cancer screening in low-resource settings, specifically among the vulnerable population of HIV-infected women. This could exponentially increase options for cervical cancer screening in low-resource settings and add another choice for screening women in all parts of the world."
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2010 GRANTEE
Samuel W. French, M.D., Ph.D.Assistant Professor, University of California, Los Angeles, Los Angeles, CA
Quercetin: A New Hepatocellular Carcinoma Prevention Paradigm
"Chronic hepatitis C viral (HCV) infection is the number one causative agent of cirrhosis necessitating liver transplantation and is the major cause of the recent doubling of hepatocellular carcinoma in the United States. We have identified heat shock proteins (HSP)s 40 and 70 as cellular proteins that interact with the HCV protein NS5A and are important for HCV infection. We have further demonstrated that heat shock protein synthesis inhibitors (HSPSI)s efficiently reduce viral infection with no toxic effect in cell culture. One of the HSPSIs we identified, Quercetin, is a naturally occurring bioflavonoid that has shown no significant side effects in patients in other published studies. Therefore, we will conduct a dose escalation clinical trial primarily to determine the highest safe dose of Quercetin in patients who have chronic HCV. We will also determine if Quercetin treatment lowers viral levels in the blood. These studies have the potential to lead to non-toxic treatments of chronic HCV infection thereby reducing the incidence of cirrhosis and hepatocellular carcinoma. I need to thank the unwavering support of the UCLA Department of Pathology. I must also thank Drs. Asim Dasgupta, Ren Sun, Vaithilingaraja Arumugaswami and Santanu Raychaudhuri who were absolutely essential in providing me reagents and guidance that allowed me to establish my hepatitis C/hepatocellular carcinoma research program. The Landon Foundation-AACR INNOVATOR Award for Cancer Prevention Research will provide me with this first opportunity to apply my laboratory findings to the clinical aspect of cancer prevention."
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