Chapel Hill, NC - Seven UNC Lineberger scientists were awarded research funding for their proposals in Population Sciences and Clinical/Translational Sciences. The grants are submitted to and reviewed by a committee of faculty experts, and the competition is keen. Here are brief descriptions of the seven projects.

Population Sciences

Adam Goldstein, MD
Tobacco Cessation Programs for Cancer Patients in NCI-Designated Cancer Centers in the US

Dr. Goldstein’s research will examine specific smoking cessation services offered at the 56 NCI-designated cancer centers: accessibility and scope of services, program funding, and factors associated with having a comprehensive tobacco cessation program.

Daniel Reuland, MD
Development and Testing of a Spanish Language Colorectal Cancer Screening Decision Aid

Dr. Reuland will develop a Spanish language colon cancer screening decision aid based on the English version and make it more culturally appropriate for Latinos. He will hold focus groups to determine what makes it difficult or easier to obtain a colon cancer screening test.

Clinical/Translational Sciences

Ian Davis, MD, PhD
Genome-wide Identification of Active Regulatory Elements in Fresh and Archival Human Cancers

Cancer is often associated with genetic changes that alter the molecular switches critical for the control of gene expression. Understanding how genes are inappropriately turned on or off offers biological insights into cancer development and may lead to therapeutic strategies. Up to this point, examining gene regulation meant looking at the products of genes, RNA. RNA studies have been increasingly applied to discriminate between different cancers and to predict response to therapy. However, in clinical practice most tissues are not preserved in a form that permits convenient or high quality RNA isolation, an issue particularly relevant for the majority of patients who receive their care in community hospitals.  This limitation significantly compromises the ability to widely capitalize on these advances to the benefit of patients. We propose comprehensive identification of critical DNA regions that function to regulate genes through the application of two complementary strategies that permit examination of the entire human genome. Specifically, we will discover differences between the DNA of human tumors and adjacent normal tissues. With a goal of expanding these techniques using tissues that have been chemically preserved and embedded in paraffin, the most prevalent and accessible form usually retained by pathologists. Once optimized and validated, we anticipate that these techniques will enable the study of gene regulation in cancer in the vast archives of currently available clinically annotated tumor specimens.

Laura Raftery, MD

Primary Resistant or Locally Recurrent Rectal Cancer after Chemotherapy and Surgery: The Role of Insulin Like Growth Factor-1 Pathway and αVβ3, An Associated Transmembrane Protein

Preoperative chemotherapy and radiation (CRT) are the standard of care for stage III and IV rectal cancer to improve surgical outcome and prevent local recurrence, which can be devastating. Compared to non-diabetic patients, diabetic patients are more resistant to therapy. Certain proteins(αVβ3) and growth factors (insulin-like growth factor)  may have roles in CRT resistant rectal cancer.

Little is known about the importance of this growth factor’s signaling in rectal cancers’ response to CRT, either in diabetic or in non-diabetic patients. Still less is known about the cooperative signaling of αVβ3and the growth factor in rectal cancer development, tumor cell survival and cancer recurrence, but we predict that hyperinsulinemia ( too much insulin)  and insulin resistance lead to cancer causation and tumor cell survival via enhanced activation of the growth factor’s pathway. We hope to prove that this growth factor and protein are more abundantly activated in patients with primary resistant and recurrent rectal tumors compared to those patients achieving pathologic complete remission. If our hypotheses are correct, we would establish that targeting this growth factor is of potential value for patients with rectal cancer who could be selected for therapy based on activation status of the growth factor and/or the protein.

M. Patricia Rivera, MD

Recruitment of Patient Cohorts for Profiling of Gene Expression in the Diagnosis and Management of Lung Cancer

Lung cancer is the leading cause of cancer death in the United States. The majority (75%) of new lung cancers are diagnosed in the locally advanced or distant disease stage, at a higher rate than breast, colon and prostate cancers, for which there are screening programs. Currently, there is not an approved screening program for lung cancer.

Identifying high risk patients requires huge advances in screening methods. Cigarette smoke induces effects on gene expression in bronchial lining tissue of smokers. Recent studies have reported a predictive biomarker set of genes generated from comparison of gene expression in bronchial lining tissue from smokers without or with lung cancer. This approach increases the diagnostic sensitivity of the bronchoscopy procedure for patients with lung cancer and holds potential for screening high-risk groups.

A major impediment to applying this procedure is that it requires bronchoscopy to sample bronchial epithelium for gene expression analysis. Based on data demonstrating a similarity of cigarette smoke effects on a type of dysfunction in nasal lining tissue and bronchial lining tissue, we hypothesize that similar diagnostic effects of cigarette smoke will be detectable in nasal lining cells as exhibited in bronchial lining tissue. We propose to test this hypothesis by comparing nasal with bronchial gene expression profiles in patients being evaluated for suspected lung cancer. If gene profiling of nasal lining tissue can identify patients at risk who will develop lung cancer, the capacity to obtain diagnostic samples via simple nasal scrapes as compared to bronchoscopy will revolutionize lung cancer screening.

Julian Rosenman, MD

Improving Head and Neck Cancer Therapy by Developing a Means to Precisely Quantify Patient Set-Up Error in Real Time

Effectively treating head and neck cancers with conformal radiotherapy requires accurate dose delivery. Patients undergoing this type of therapy can compromise the precision of their dose delivery as they are prone to making unintended head rotations. Because even slight rotational movements can result in unacceptable delivery errors, radiotherapists stabilize patients with form-fitted thermoplastic masks. Even within these masks, however, patients can still often unintentionally rotate their heads.

Proposed is a non-imaging method of detecting patient movements and set-up errors by using multiple ultra-thin pressure sensors located within the inside of the form-fitted masks. This inexpensive adaptation of current stabilization technology will eventually enable radiation oncologists to dynamically and automatically adapt a patient’s treatment plan in real time based on any deviations that occur from their intended position. This project, which is an interdisciplinary collaboration between investigators in Radiation Oncology and Biomedical Engineering, will involve optimizing the pressure sensor configuration within the mask, calibrating these sensors with existing imaging methods of alignment, and attempting to measure changes in patient head position to within 1 mm.

This resolution is currently unavailable with non-imaging methods of patient alignment, nor is there any current method to track patient position during therapy and adapt their treatment accordingly. If successful, this system has the potential to significantly improve the quality of care provided for patients with head and neck cancer.

Xiaoying Yin, MD, MS
Co-PI: D. Neil Hayes, MD, MPH

MicroRNA Alteration in Human Head and Neck Squamous Cell Carcinoma

An increasing line of evidence has indicated that molecules called miRNAs are tightly connected with the process of cancer causation. Several miRNAs have demonstrated activity as tumor suppressors or oncogenes in many types of cancer. miRNAs are differently expressed in normal and tumor tissue as well as between tumor subtypes. These differences may be useful as prognostic and predictive markers in cancer patients. Some miRNAs have been identified as biomarkers to predict chemotherapy response or patient survival in certain types of cancer.

Currently, there has been no comprehensive study of miRNAs’ role in primary human head and neck squamous cell carcinoma (HNSCC). The aim of this study is to investigate the expression patterns of miRNA in human HNSCC and determine the diagnostic and predicting utility of specific miRNA alteration in the assessment of HNSCC patients and ultimately use this information to evaluate the relationship of the clinical courses of HNSCC with miRNA signature in a clinically-relevant setting. Additionally, this project fits into a larger endeavor currently underway in our lab. We have initiated a comprehensive survey of genomic alterations in cancer all within a defined cohort of patients for whom the clinic histories have been obtained.