Molecular studies of carcinomas
In our laboratory we study human tumors with the ultimate goal of developing new diagnostic markers, new biomarkers for prognosis and response to treatment and to develop novel therapeutic targets. We use and develop a range of techniques that focus on extracting genomic and proteomic data from patient derived archival material (formalin-fixed paraffin-embedded (FFPE).
Ductal carcinoma in situ progression in breast cancer
With the advent of screening mammography, there has been a remarkable rise in the diagnosis of DCIS among asymptomatic women without the expected reduction in breast cancer mortality, leading to concerns about over-treatment. We identify genomic and phenotypic changes in DCIS that develop IBC. We are also developing new technologies to allow us to perform gene expression profiling on specimens for which no frozen tissue is available. For example, we are combing FFPE-based NGS with laser capture microdissection to capture localized microscopic entities such as in situ carcinoma and precursors thereof. This work is supported by funding from the NIH PreCancer Atlas and the Molecular Characterization Laboratories.
Recent suggests that in the U.S. prostate cancer is over-detected and over-treated resulting in significant morbidity and financial costs. While many prostate cancers should be managed with active surveillance, uncertainties surrounding available clinical tools of aggressiveness (such as PSA, Gleason score and clinical stage) will often drive patients and physicians to treatment. We hypothesize that early prostate cancer arises from definable molecular alterations in precursor lesions and progresses as a result of acquired lesions that confer aggressive features in a subpopulation of cells in precursor lesions and/or early tumors. We are defining the earliest genomic events on the pathway to invasive carcinoma to examine the key genomic features distinguishing good and bad outcome prostate cancer. We are using technologies we have developed to analyze small samples in both fixed and frozen tissue to provide a complete picture of the early events in prostate carcinogenesis. This work is supported by funding from the NIH.
Head & Neck cancer
Our focus in head and neck cancers is current on nasopharyngeal carcinoma (NPC) and ameloblastoma.
NPC is a malignant neoplasm of the nasopharynx with a high incidence in Southern Asia and in other endemic areas. Though it is exquisitely sensitive to radiation (XRT), NPC remains clinically challenging due to distant metastases. There is an urgent need to understand which patients are at risk for distant metastases and to tailor therapy for these patients. Biomarkers for NPC outcome are limited. We hypothesize that NPCs differ in the type and accumulation of genomic alterations and that measuring these will help us identify cases that have a high likelihood of progressing to distant metastases and poor outcomes. We are generating a clinical classifier of risk by combining the most informative features from these genomic analyses. Our goal is to provide more relevant and predictive clinical results to patients at the time of diagnosis that will more appropriately guide immediate therapy with the ultimate goal of reducing incidence of and mortality from NPC, while at the same time avoiding unnecessary interventions.
Ameloblastoma is a rare but aggressive tumor of the jaws. We have recently identified driver mutations in both mandibular and maxillary ameloblastomas which has lead to a clinical trial at Stanford. We are currently pursuing genomic studies to identify additional biomarkers that would predict response and aid in diagnosis.