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Despite decades of research, chemotherapy for cancer is still very much an inexact science. Two major issues -- delivery of therapeutic agents directly to cancer cells with minimal impact on the rest of the body and preventing recurrence of the cancer in a more resistant form after treatment -- are being addressed by CAS Biology Professor David Waxman and associates.
Last year Waxman and colleagues at Massachusetts General Hospital and the Dana-Farber Cancer Institute licensed a new gene therapy approach for generating an active chemotherapeutic drug directly at the site of the tumor target. The therapy is based on P450, a naturally occurring liver enzyme necessary to activate the commonly used chemotherapeutic agent cyclophosphamide. Studies have shown that this approach has the potential to eradicate tumors using lower concentrations of cyclophosphamide, drastically reducing damage to healthy cells. The licensee, London-based Oxford BioMedica, is now testing the therapy's efficacy in breast and ovarian cancer.
Recent studies by Waxman and his associate, Youssef Jounaidi show that the effectiveness of this therapeutic strategy can be greatly enhanced by implementing a schedule of cyclophosphamide administration which includes an additional component that cuts off the tumor's access to nutrients via the blood supply. This strategy, described in the June 1, 2001 issue of the journal Cancer Research, leads to a dramatic shrinkage of even large tumor masses.
The second issue, preventing a resistant recurrence, is being addressed by Pamela Schwartz (GRS'02), one of Waxman's Ph.D. students. She recently presented her work at BU's Science Day, winning the Community Technology Fund Award for research with high potential for producing a commercial product.
Schwartz's work builds on the knowledge that patients who have high levels of the protein Bcl-2 have a poorer prognosis for recurrence of cancer. The presence of Bcl-2 in cancer cells causes them to arrest -- that is, to remain in a dormant phase of the cell cycle -- rather than die when they are exposed to a chemotherapeutic agent. In this case, the cancer may go into remission, but since the cells can reactivate at any point, the cancer can recur.
Schwartz's research revealed the critical role that Bcl-2 plays in regulating
cyclophosphamide-induced cell death. With this knowledge she is now investigating ways to counteract the effects of Bcl-2. One approach seeks to used genetically-based methods to lower Bcl-2 levels, enhancing the sensitivity of tumor cells to P450 activated cyclphosphamide. |
