Multimodal Functional Imaging of Head and Neck Cancers
Radiologic techniques are important components of the diagnostic and prognostic armamentarium in oncology. Research under this theme is focused on the application of magnetic resonance imaging (MRI), and optical molecular imaging techniques in preclinical and clinical studies to study oral cancer biology and their response to traditional and novel anticancer treatments. Studies in the laboratory have demonstrated the utility of multimodal imaging methods in guiding treatment design. The Seshadri lab was the first to apply novel optoacoustic imaging methods PAI for functional imaging of salivary glands and for monitoring the response of tumor and salivary gland response to radiation. These studies led to the recent award of an R01 grant by the National Cancer Institute that is focused on the application of these methods for functional assessment of salivary glands in small and large animal models of oral cancer with the ultimate goal of clinical translation. Ongoing studies are focused on validation and clinical application of photoacoustic imaging in head and neck oncology, specifically to assess the response of head and neck tumors to chemoradiation therapy. To this end, a first-in-human clinical trial will be initiated at Roswell Park.
Rich LJ, Winslow TB, Alberico RA, Repasky EA, Seshadri M, Singh AK. Enhanced tumour perfusion following treatment with water-filtered IR-A radiation to the thorax in a patient with head and neck cancer. Int J Hyperthermia. 2016 Aug;32(5):539-42.
Rich LJ, Seshadri M. Photoacoustic monitoring of tumor and normal tissue response to radiation. Sci Rep. 2016 Feb 17;6:21237.
Chemoprevention of Oral Cancer
Recently, we have demonstrated the chemopreventive potential of combining vitamin D with epidermal growth factor receptor (EGFR) inhibition against oral cancer (Bothwell et al., Cancer Prev Res. 2015; Featured on the Cover). This work led to the recent award of an R01 grant (2016-2021) by the National Institute of Dental and Craniofacial Research (NIDCR). Ongoing studies are examining the impact of vitamin D on various stages of oral carcinogenesis and understanding the mechanisms of interaction between vitamin D and EGFR inhibitors to maximize therapeutic benefit.
Bothwell KD, Shaurova T, Merzianu M, Suresh A, Kuriakose MA, Johnson CS, Hershberger PA, Seshadri M. Impact of Short-term 1,25-Dihydroxyvitamin D3 on the Chemopreventive Efficacy of Erlotinib against Oral Cancer. Cancer Prev Res (Phila). 2015 Sep;8(9):765-76.
Verma A, Rich LJ, Vincent-Chong VK, Seshadri M. Visualizing the effects of metformin on tumor growth, vascularity, and metabolism in head and neck cancer. J Oral Pathol Med. 2018 Mar 23
Dissecting the HPV and Angiogenesis link in HNSCC
HPVs are DNA viruses that exhibit squamous epithelial tropism. The oncogenic potential of these high-risk HPV strains is related to the ability of the viral oncoproteins E6 and E7 to functionally inactivate p53 and pRb, which results in chromosomal instability, increased proliferation, and loss of cell cycle regulation among other biological consequences. In SCCHN, HPV-16 is the most commonly associated strain that accounts for a majority of HPV positive tumors. Clinical studies have shown that patients with HPV positive tumors (predominantly nonsmokers) respond more favorably to conventional anticancer therapies than HPV- tumors. Favorable outcomes seen in patients with HPV+ tumors have been attributed to increased radiosensitivity of these tumors, absence of field cancerization, and induction of immune responses to viral antigens. However, little is known on the influence of HPV on the tumor microenvironment and response to vascular targeted therapies. To address this gap in knowledge, we are currently investigating the tumor architectural and vascular differences between HPV+ and HPV-HNSCC using patient-derived xenograft (PDX) models and human tumor tissue microarrays (TMAs). These studies have revealed significant differences in vascular morphology, function and susceptibility to vascular-targeted therapies between the two types of HNSCC.
Bothwell KD, Folaron M, Seshadri M. Preclinical Activity of the Vascular Disrupting Agent OXi4503 against Head and Neck Cancer. Cancers (Basel). 2016 Jan 7;8(1).