The latest roundup of cancer research by University of Chicago experts highlights work being done in kinase inhibitors, genomics of breast cancer, differences between HPV-related and other head and neck cancers, and immunotherapy and host immune suppression.
These members of the University of Chicago Medicine Comprehensive Cancer Center are making great advances in the understanding and treatment of cancer and their work, published in peer-reviewed scientific and medical journals, does not always get a lot of external publicity.
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Phase I trial targets the MET Pathway in advanced solid cancers
The MET receptor tyrosine kinase is frequently up-regulated in cancers and is implicated in driving invasion and metastasis. In this Phase Ia and Ib study involving Ravi Salgia, MD, PhD, professor of medicine; Daniel Catenacci, MD, assistant professor of medicine; Mark Ratain, MD, Leon O. Jacobson Professor of Medicine; and Blase Polite, MD, assistant professor of medicine, patients with advanced solid cancers were given a biological MET inhibitor, onartuzumab, as a single agent and in combination with bevacizumab (a VEGF inhibitor). The research team showed that these treatment modalities were well tolerated and generated a durable complete response in at least one patient, and the work provides a foundation for Phase II studies. (Salgia et al., Clin Cancer Res, Feb 3 Epub ahead of print, 2014)
A new breast cancer gene is identified
Through a genome-wide association study of women with early-onset breast cancer, UCCCC researchers Habibul Ahsan, MD, MMedSc, Louis Block Professor of Health Studies, Brandon Pierce, PhD, assistant professor of health studies, and Nancy Cox, PhD, professor of medicine, discovered that many single nucleotide polymorphisms were associated with both early-onset and late-onset breast cancer, including SNPs on chromosome 5q11.2. A novel gene-based analysis identified as association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11. Given that the enzyme encoded by this gene catalyzes a key step in glycolysis, and that tumor cells often have altered glucose metabolism, it is possible that PFKM expression may, in fact, be a novel determinant of breast cancer risk. (Ahsan et al., Cancer Epidemiol Biomarkers Prev, Feb 3 Epub ahead of print, 2014)
Innovative modeling and imaging approaches assess oral cancer response to therapy
Human papillomavirus (HPV)-associated oral cancers differ in their molecular features and responses to therapy from other head and neck squamous cell cancers (HNSCC), and, therefore, require novel approaches for treatment. Michael Spiotto, MD, PhD, assistant professor of radiation and cellular oncology, in collaboration with Charles Pelizzari, PhD, associate professor of radiation and cellular oncology, recently developed a preclinical genetic model in which HPV protein-induced oral tumors could be followed with bioluminescence. The investigators showed that treatment of this model with rapamycin, an mTOR inhibitor, or image-guided radiotherapy caused tumor regression and reduced bioluminescence. The impact of the work is an enhanced ability to visualize tumor growth and response to novel interventions, including drugs and radiotherapy approaches. (Zhong et al., Cancer Res, Feb 13 Epub ahead of print, 2014)
Adoptive transfer of T cells eradicates established tumors
One approach for tumor immunotherapy is adoptive transfer of tumor-specific T-cells; yet, there has been concern that this therapeutic strategy will be ineffective because of host immune suppression. Recent work by Hans Schreiber, MD, PhD, professor of pathology, in a collaborative effort with Theodore Karrison, PhD, associate professor of health studies, recently showed that this may not be the case. Using in vivo imaging of preclinical models, they found that adoptively transferred immune T cells eliminated well-established tumors in the presence of suppressive myeloid cells by destroying tumor blood vessels and tumor cells themselves. These findings indicate that adoptive transfer of T cells can overcome local and system immunosuppression caused by myeloid cells and that this may be an attractive strategy for cancer treatment (Arina et al., J Immunol 3:1286-93, 2014).