Combination therapy drives cancer into remission

Researchers have achieved an experimental breakthrough in the simultaneous use of two or more agents for treating cancer, known as combination therapy. If it is shown to be safe and effective in humans, the therapy outlined by the new study is a promising general strategy for treating many cancers that do not respond to current therapies.

A two-drug combination therapy, published in tomorrow's issue of the journal Nature, led to the complete remission of a mouse model of B-cell lymphoma in all of the treated animals. In contrast, animals treated with either drug alone (rapamycin or doxorubicin) rarely experienced complete remission.

The study, led by Dr. Scott Lowe of Cold Spring Harbor Laboratory, establishes a new paradigm for overcoming chemotherapy resistance in many forms of cancer.

Rational Target Selection and an Off-the-Shelf Chemotherapeutic "One-Two Punch" for Lymphoma and Other Cancers

Pre-cancerous cells can be eliminated from the body by a natural self-destruct mechanism--normally active in many types of cells--called programmed cell death. Unfortunately, a hallmark of most cancers is a defect in programmed cell death that enables pre-cancerous cells to survive, proliferate out of control, and form a tumor.

Because most traditional chemotherapy agents act by triggering programmed cell death, such agents are frequently ineffective against tumors that lack a functional programmed cell death mechanism. Such tumors are said to be chemotherapy-resistant. The evasion of treatment-induced programmed cell death by chemotherapy-resistant tumors has been a major impediment to successful therapeutic outcomes for human cancer.

Lowe and his colleagues reasoned that--like a one-two knockout punch in boxing--using one drug to restore the programmed cell death mechanism and a second drug to trigger the process might reduce or eliminate chemotherapy-resistance and be an effective strategy for treating cancer.

Contact: Jeff Picarello
Cold Spring Harbor Laboratory

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