Developmental Therapeutics

Protein-targeted agents are valuable therapeutic tools in head and neck cancer, and other cancers. Development of next-generation agents with still greater efficacy involves detailed understanding of the molecular basis by which these agents bind and inactivate their targets in tumors. The Dunbrack group concentrates on research in computational structural biology, including homology modeling, fold recognition, molecular dynamics simulations, and bioinformatics. In developing these methods, the group uses methods from various areas of mathematics and computer science, including Bayesian statistics and computational geometry. In collaboration with other Program scientists (Robinson, Adams, Astsaturov, Golemis), the Dunbrack group makes models of cancer-relevant protein targets, enabling basic research and therapeutic development. Read More »

Targeted cancer therapies use small molecules (drugs) to block the function of proteins that support cancer. The Jaffe lab performs fundamental studies of protein structure to support new strategies for targeting protein function with small molecules. Emphasis is placed on control of a newly discovered protein structure dynamic. For example, cancer related protein molecules such as EGFR, p53, and integrase undergo dynamic interactions with additional copies of themselves: these larger complexes are known as quaternary structure assemblies. For each of these proteins, it may be possible for the protein assembly to dissociate into its individual protein molecules, for each of these molecules to change conformation, and for the protein to then assemble to a structurally and functionally distinct quaternary structure assembly. Research in the Jaffe laboratory addresses the idea that it may be possible for small molecules to bind to a specific assembly and manipulate this equilibrium for therapeutic advantage. Dr. Jaffe's collaborations include Murphy (p53), Skalka (integrase), Golemis (EGFR) and also collaborating members Chernoff and Peterson, to design small molecule agents targeting Ras and Pak protein interactions, and other targets. Read More »

Cancer is caused by changes that affect specific proteins. Many valuable targeted therapies use small molecules (drugs) and antibodies to block the activity of cancer-associated proteins. In order to understand the fundamental mechanisms by which cancer-associated mutations act, and to better design new targeted therapies, it is critical to be able to study protein folding and structure at a very high level of resolution. Research in the Roder group is aimed at understanding the principles that govern the folding of globular proteins. The group explores the early stages of protein folding by coupling advanced rapid mixing methods with structurally informative conformational probes, such as intrinsic and extrinsic fluorescence probes, and protection of individual amide hydrogens from solvent exchange monitored by NMR. The group also participates in collaborative studies involving NMR and other spectroscopic methods aimed at elucidating the structure, dynamics and macromolecular interactions of proteins of intense biomedical interest, working with the Robinson, Dunbrack, and Murphy groups to address problems relevant to cancer of the head and neck. Read More »

Dr. Astsaturov is a clinical/laboratory investigator who sees patients with GI cancers and directs a lab focused on development of new treatment strategies utilizing a systematic synthetic lethal screening approach to identify new signaling proteins that can be blocked simultaneously with EGFR. Read More »

Dr. Golemis is co-leader of the Developmental Therapeutics Program and also is a co-leader of the Keystone Program in Head and Neck Cancer. The Golemis group seeks to define the changes in cell signaling that occur as tumors spread by metastasis and develop resistance to drugs, with the ultimate goal of inhibiting these processes. Research in the laboratory has two major themes. One set of research projects focuses on study of the Cas protein family, a group of proteins that provides a hub assembling groups of signaling proteins essential to cancer progression. Complementary projects, performed in collaboration with Fox Chase Cancer Center physician-scientists (particularly Igor Astsaturov) use computer-based bioinformatic approaches and mid-throughput screening to identify genes that sensitize cells to targeted and classic cancer therapies. Read More »

A major problem in cancer therapy is resistance to chemotherapeutic agents. The Multidrug Resistance Proteins (MRPs) are a family of proteins that pump toxic chemicals out of cells. Although MRP proteins provide a useful defense mechanism against environmental toxins, abnormally increased activity of some of these proteins in cancer causes problems for effective management of tumors. The Hopper-Borge group studies one of the more recently discovered MRP subfamily members, MRP7, which is abundant in head and neck cancer cells, and confers resistance to various drugs including the taxanes (paclitaxel and docetaxel) and other drugs that are used in the treatment of head and neck cancers. Read More »

Cell migration and adhesion are essential processes for cell differentiation, tissue formation, organism development, and morphogenesis. Enhancement of cell migration and reduction of cell adhesion are key characteristics of tumor metastasis. Both cell migration and cell adhesion are actin-dependent processes: cell migration is governed by actin polymerization or exocytosis induced cell extension at the leading edge; cell adhesion is driven by the binding of a group of actin skeleton-associating proteins to the extracellular matrix. Our research interest is to elucidate the three-dimensional structures and signaling functions of protein in the MRL family, a group of adapter proteins capable of regulating cell migration and adhesion in normal and cancer cells, and to study related signaling components and events. The main experimental technique we employ for three-dimensional structure determination is protein crystallography. Read More »

Dr. Yeung uses proteomic technologies to identify the signaling changes characteristic of cancer. Yeung uses proteomic technologies to identify the signaling changes characteristic of cancer. Through collaborations with Bellacosa, Clapper, Cooper, and Knudson he demonstrated one-hit gene-specific effects in Familial Polyposis Coli and BRCA1 and BRCA2 mutation carriers, and established a reference 2D gel proteome database for human colon crypt proteins. He has demonstrated (with Weinberg and S Cohen) that mass spectrometry can detect current clinical biomarkers of mucinous cyst adenomas in as little as one microliter of pancreatic cyst fluid, offering the possibility of early detection. Read More »

Dr. Adams is co-leader of the Developmental Therapeutics Program. Monoclonal antibodies are pure, defined preparations of antibodies that can be used to block the action of individual proteins associated with cancer. Monoclonal antibodies that bind EGFR family members are valuable tools in non-surgical treatment of a wide variety of cancers. The Adams lab is focused on understanding the role of the strength of antibody binding on tumor targeting and therapeutic efficacy. Research from this group addresses the idea that optimizing the binding affinity of antibodies for their target protein could enhance their efficacy in the treatment of cancer. The Adams lab is also collaborating with program members Dunbrack and Robinson to employ molecular modeling strategies to develop antibodies that target novel tumor antigens. Read More »

Dr. Borghaei is a medical oncologist treating patients with lung cancer and Director of the Lung Cancer Risk Assessment Program at Fox Chase. His laboratory is interested in monoclonal antibodies and antibody-dependent cellular cytotoxicity (ADCC). In addition to developing new monoclonal antibodies, he is conducting clinical trials exploring the immunological responses that occur as a result of cetuximab therapy-associated ADCC, with the goal of augmenting these immune responses to achieve improved efficacy of antibody therapy. He is involved in a number of clinical trials with various monoclonal antibodies. His latest lung cancer trial explores the relationship between EGFR and Aurora Kinase in lung cancer, in collaboration with Astsaturov. Read More »

Dr. Burger's research interests include targeted therapy of ovarian cancer, ovarian cancer risk assessment and prevention and developmental therapeutics for gynecologic cancers. Read More »

Dr. Burtness is a co-leader of the Keystone Program in Head and Neck Cancer. Her studies of EGFR-directed therapies are directed at personalizing optimal treatments for patients based on the clinical features of their cancer. She is an accomplished clinical investigator with specific expertise in the treatment of head and neck, esophageal, pancreatic and colorectal cancers. She has shown that high EGFR expression predicted resistance to cetuximab in head and neck cancers. She chairs an investigator-initiated phase I study of cetuximab with escalating doses of the mTOR inhibitor everolimus to target signaling from pAkt, and an investigator-initiated phase II trial in head and neck cancer of chemotherapy plus cetuximab, followed by addition of erlotinib to target nuclear EGFR and enhance inhibition of membrane-bound EGFR. Read More »

Dr. Buyyounouski is working to develop new treatment techniques, using IMRT, that help men preserve erectile function following radiation therapy for prostate cancer. Currently, I am a co-primary investigator of this clinical trial at Fox Chase. I am also developing a technique to detect recurrent prostate cancer earlier using MR spectroscopy and repeat prostate biopsy, with funding from the Radiological Society of North America (RSNA). This will be available as part of a clinical trial. I am a co-author of several research papers and book chapters on prostate cancer, IMRT and testicular cancer. Read More »

Dr. Chen is a radiation physicist who is known for her pioneering work on MRI-guided high-intensity focused ultrasound for radiotherapy. The potential clinical applications of this new technology for cancer treatment include brain cancer, breast cancer, liver cancer, prostate cancer and bone metastases. Read More »

Dr. Cohen is the Acting Director of the GI Medical Oncology Program and an exceptionally active and productive clinical and translation investigator as well as serving as Associate Medical Director, Fox Chase Cancer Center Partners and Extramural Research Programs. Read More »

The overall goal of our research is to discover ways to improve the treatment of epithelial ovarian cancer (EOC). Our laboratory is interested in defining the precise molecular mechanisms of peritoneal dissemination of ovarian cancer cells to identify specific molecular targets for therapeutic intervention in patients. Using a combination of in vitro and in vivo approaches, we hope to better understand EOC tumor biology at the cellular level as well as disease development and progression in animals. Read More »

Dr. Doss is a Medical Physicist in the Diagnostic Imaging department here at Fox Chase. His research interests are in two broad areas: (1) Health Effects of Low Dose Radiation and (2) PET Imaging in Oncology Read More »

In an effort to contribute to the reduction of both the incidences of breast cancer and the morbidity and mortality due to this disease, we have developed a multidisciplinary program encompassing basic, clinical, and prevention and control research. Read More »

The clinical trials available at Fox Chase give patients access to more treatment options and the hope of improving cancer treatment for future patients. I have a special interest in targeted-therapies, which have become important to the future of cancer treatment. These therapies have the potential to reduce toxic side effects and improve control of disease. Specific areas of research interest include the clinical management of melanoma, and of gynecological cancers such as ovarian cancer. In contrast to breast cancer, which often responds well to treatment and yields a complete cure, ovarian cancer typically recurs in a form resistant to initial treatment. Read More »

Dr. Mehra is a medical oncologist who specializes in the treatment of lung cancer and cancers of the head and neck, including thyroid cancer. She is a member of the Keystone Program in Head and Neck Cancer. Evidence is now available for head and neck and other cancers that high protein expression of ERCC1 predicts resistance to cisplatin. An important goal in personalizing therapy in head and neck cancer is to establish whether ERCC1-guided therapy can spare certain patients the toxicity of high dose cisplatin treatment, while maintaining or improving on patient outcomes. Mehra has collaborated with Godwin to utilize highly quantitative immunofluorescence (AQUA) in situ proteomics to demonstrate the range of ERCC1 expression in head and neck cancers, to help identify patients for specific treatment regimens She is focused on bringing novel targeted therapies into the clinic. Read More »

I collaborate with Dr. Paul Cairns on a project in our Ovarian Cancer SPORE exploring the role of epigenetic modification of genes in cancer development, prognosis and response to treatment. I am the principal investigator for clinical trials of the Gynecologic Oncology Group (GOG) and sit on the GOG's developmental therapeutics and ovarian cancer committees. Working through the GOG, I am the principal investigator of an international clinical trial evaluating intraperitoneal chemotherapy combined with anti-angiogenesis therapy in the treatment of ovarian cancer. Read More »

Development of receptor-tyrosine kinase inhibitors. Read More »

Dr. Ridge is a co-leader of the Keystone Program in Head and Neck Cancer, and 2009 President of the American Society of Head and Neck surgeons. His clinical practice focuses on head and neck and endocrine tumors, including nonsurgical management, organ preservation, new surgical techniques and early and advanced thyroid tumors. Read More »

Dr. Robinson is focused on developing antibody-based therapeutics designed to exploit the abnormal cellular signaling networks that drive cancer formation and progression. Overexpression of the EGFR receptor in head and neck squamous cell carcinoma (HNSCC) is correlated with aggressive disease and poor patient outcome. Despite this correlation, therapies that target and block EGFR (e.g., the antibody cetuximab (Erbitux) and drugs such as erlotinib (Tarceva) and gefitinib (Iressa)) have modest clinical efficacy in many patients. One reason for this modest efficacy may be that EGFR is one of a small "family" of proteins which have similar tumor-promoting activities: in some treatment-resistant tumors with blocked EGFR, its relative ErbB3 may be compensating for its functions. Recent work from a number of laboratories has suggested that ErbB3 plays a role in the development of resistance to erlotinib and gefitinib in a number of cancers. The Robinson laboratory has developed a set of therapeutic antibodies that simultaneously block EGFR and ErbB3. They are testing the idea that these antibodies will be efficacious in the setting of HNSCC, and could potentially reverse acquired resistance to EGFR-targeting drugs. They are also working collaboratively with the Dunbrack and Roder groups to design further enhanced antibodies targeting the EGFR protein family. Read More »

My research efforts in two areas. First, I work closely with the Chief Scientific Officer and the Executive Committee of Research to build stronger collaborative scientific efforts through the strategic investment of Center resources to enhance team based science. In addition, I continue my efforts to explore translational research strategies in the management of women with ovarian cancer. Read More »

Our laboratory investigations focus on clinical studies to improve the response of tumors to drug therapies, and on animal studies to investigate methods to enhance drug delivery and decrease toxicity. Read More »

Dr. von Mehren is the Director of the Sarcoma Program and a medical oncologist who specializes in sarcoma. She collaborates with Godwin to investigate the biology of gastrointestinal stromal tumors (GISTs) and markers of response to various tyrosine kinase inhibitors. Her clinical research focuses on the evaluation of novel agents for the treatment of sarcomas. Read More »

Dr. Yangs research includes: 1) Application of Immunohistochemistry (IHC) for both basic and clinical research, and 2) Gene regulation on embryogenesis, organogenesis, tumorigenesis and multi drug resistance. Read More »

Dr. Yu is a nuclear medicine physician with expertise and interest in the use of PET for diagnostic and molecular imaging. He has developed unique collaborations with groups developing novel imaging agents, brought these agents to Fox Chase and successfully completed their initial evaluation in humans. Yu is evaluating novel tracers targeting hypoxic tissue and angiogenesis in Phase 0 trial. Yu is also the authorized user for many other new radioactive tracers under IND and currently in various clinical trials at FCCC. Read More »