UPCI investigators are pioneering research to advance personalized cancer treatments. Below are some examples from several UPCI research programs.
Brain Tumor Program (BTP)
The Brain Tumor Program (BTP) currently runs “personalized” clinical studies based on patients’ gene markers, such as human leukocyte antigen (HLA)-A2, epidermal growth factor receptor (EGFR) variant III and chromosome 1p/19q co-deletion. In addition, the BTP offers a host of molecularly targeted treatment approaches for children whose brain tumors have genomic alterations that make them ideally suited for specific novel-agent trials. These include studies of MEK inhibitors (e.g. AZD6244) for children with BRAF-altered low-grade gliomas and Sonic hedgehog (SHH) inhibitors for children with medulloblastomas that have alterations in the SHH signaling pathway, which are being conducted by the NCI-supported Pediatric Brain Tumor Consortium (in which Pittsburgh is a founding member). Because such alterations are common, they apply to a significant subset of patients with these tumor types.
Cancer Epidemiology, Prevention, and Control Program (CEPCP)
Members of the Cancer Epidemiology, Prevention, and Control Program (CEPCP) are engaging in research projects that could lead to the identification of individuals with the same or similar characteristics or genetic traits who may be more susceptible to cancer risk or more favorable responses to certain treatment. One of our research goals is to identify individuals who are at very high risk for cancer to whom the cancer prevention or early detection strategies could be developed and applied. Some call this approach “personalized” disease prevention and control.
Head and Neck Cancer Program (HNCP)
The major research focus of our Head and Neck Cancer Program (HNCP) is the identification of tumor or blood biomarkers which will help us implement “personalized” medicine for head and neck squamous cell carcinomas (HNSCC). Understanding genetic, signaling, and immune alterations in HNSCC will accomplish two goals:
- Development of new anti-cancer drugs for HNSCC, which target novel pathways; and
- Accurate identification of patients who will benefit from currently approved therapies.
Overall, in the Head and Neck Cancer Program at UPCI, we are actively exploring how to integrate candidate biomarkers into our assessment and treatment of HNSCC to deliver on the promise of “personalized” cancer medicine.
Melanoma Program (MP)
The Melanoma Program (MP) at UPCI is involved in clinical and translational research toward “personalized” cancer medicine. In fact, this is a time of rapid progress in the treatment of melanoma, with the availability of multiple highly active new molecular signaling inhibitors and promising new immunotherapies that have the ability to restore the immune response to this cancer, and to achieve long-term antitumor benefits. We are pursuing multiple new combinations of agents that are being personalized according to the presence of mutations in several categories of genes, and are developing biomarkers of immune response to the tumor that may allow us to improve the tailoring of treatment for advanced and adjuvant high-risk melanoma patients. These together may allow treatment to be given to patients who are most likely to respond to these new agents, avoiding the side effects in those who are less likely to respond to treatment. Finally, the use of adaptive designs to accelerate the development of new combinations is being explored according to these tumor molecular markers (BRAF-mutant, NRAS-mutant, or neither).
Molecular Therapeutics and Drug Discovery Program (MTDDP)
In the Molecular Therapeutics and Drug Discovery Program (MTDDP) we are developing disease-tailored new medicines, some of which are derived from complex natural products. One of our therapeutics is currently in Phase II clinical trials in the United States and Canada for the treatment of patients with advanced, recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC), colorectal carcinoma (CRC), advanced BRAF-mutant melanoma, glioblastoma multiforme, and recurrent or metastatic castration resistant prostate cancer. Several others are in preclinical or Phase I clinical trials. We are committed to the search for innovative “personalized” cures harnessing the power of small molecules.