Early cancers that remain confined to the tissue of origin and/or involve the regional lymph nodes are generally treated effectively with surgical excision and/or ablation, but may include adjuvant treatments with irradiation and chemotherapy. Treatment of disease that has spread (metastasized) to distant sites in the body requires a more systemic approach to therapy such as chemotherapy that can be administered throughout the body or regionally distributed in the setting of single organ involvement with metastatic disease. However, in the setting of metastatic disease, the efficacy of conventional anti-cancer treatments such as radiation and chemotherapy is limited by treatment resistance that occurs in as many as 50 to 70 percent of cancers derived from solid organs.

The need for more effective treatments underlies the objectives for the research conducted in the Surgical Oncology Laboratories. The research conducted in these laboratories focuses not only on expanding the understanding of tumor biology but also on extending laboratory findings to the clinic in the form of newly identified prognostic tumor markers and the development of novel therapeutic treatment strategies. The research program of the Division of Surgical Oncology is funded by the National Cancer Institute (NIH), American College of Surgeons, Industrial collaborators and Philanthropic sources.

The Surgical Oncology Research Laboratories on Jackson 9 have been newly renovated and now form the core of a Molecular Oncology laboratory in conjunction with the Division of Medical Oncology in the Cancer Center. The laboratories are funded by the National Cancer Institute, American Cancer Society, and private endowments.

The Surgical Oncology Research Laboratories have been extensively involved in training and education of both surgery residents and post-doctoral fellows. Residents and fellows have been successful in competition for national scholarships and research awards.

Residents and fellows are encouraged to present their research at national meetings and publish their data in high impact journals. The laboratory investigators collaborate closely with investigators in the Harvard Medical School, the Cancer Center, Dana-Farber Cancer Institute, and the Dana-Farber/Harvard Cancer Center.

Trainees learn advanced techniques, experimental design, data analysis, biostatistics, problem solving, manuscript preparation, and grant application preparation. Trainees gain broad experience in molecular biology, cell biology, gene cloning and characterization, cell culture, protein purification and assays, molecular virology, animal models, and clinical trial design. A list of former trainees and their publications is available upon request.

Kenneth K. Tanabe, MD:
Viruses used for gene therapy have generally been genetically engineered to prevent viral replication and to deliver transgenes to achieve a therapeutic benefit. However, viruses engineered to remain replication-competent may be exploited for cancer gene therapy because replication within cancer cells results in oncolysis.

• Genetic Engineering, Characterization, and Animal Model Testing of Herpes Simplex Viral Vectors for Treatment of Liver Metastates
• Tumor Associated Promoters for Regulation of Viral Replication and Oncolysis
• Viral Oncolysis and Antiangiogenesis
• Preclinical Toxicology in Non-Human Primates of Herpes Simplex Viral Vectors for Liver Tumor Therapy

James C. Cusack, Jr, MD:
The genotoxic effect of conventional anticancer therapy involving many chemotherapy agents and gamma irradiation results in the induction of apoptosis in cancer cells. The ability to inhibit apoptosis appears to be a principal mechanism by which resistant cancer cells are protected from chemotherapy and radiation.

• Role of NF-kB in Inhibition of Chemotherapy-Induced Apoptosis

Shyamala Maheswaran, PhD:
Our research is focused on characterizing the molecular mechanisms governing growth and tumorigenesis of the mammary gland using B-cell Translocation Gene-2 (BTG2)-mediated inhibition of breast cancer cell growth as a model system, with emphasis on determining molecular targets for mechanism-based treatment strategies and identifying potential molecular markers to predict risk and for early disease detection.

• Molecular Mechanisms Governing Growth and Tumorigenesis of the Mammary Gland

Rocco, MD, PhD:
Our laboratory is focused on understanding p16's biological role during the progression of normal huma epithelium to invasive squamous cell carcinoma.

• Identification and characterization of a novel p16-dependent checkpoint that is independent of p16's ability to elicit cell cycle arrest
• Identification of p16 upstream regulators
• Adenoviral Targeting of Dysregulated E2F Activity with p14

Sam S. Yoon, MD:
Our laboratory is investigating tumor angiogenesis, the process of new blood vessel formation in tumors, and strategies to inhibit angiogenesis in patients with sarcoma. The human body has billions of endothelial cells which line the inside of blood vessels. Tumors must induce these normally inactive endothelial cells to proliferate and form new blood vessels in order to support tumor growth beyond a very small size. This process can be a vulnerable target for anti-cancer therapies.

• Tumor angiogenesis in different organ environments: implications for anti-angiogenic therapy for soft tissue sarcomas and colorectal cancers
• Using novel anti-angiogenic and anti-tumor agents to improve the efficacy of radiation therapy for soft tissue sarcomas
• Role an endogenous calcineurin inhibitors in blocking VEGF - mediated tumor angiogenesis