Introgen's INGN 241 combined with Celebrex kills breast cancer cells

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Introgen Therapeutics, Inc. today reported the publication of preclinical data demonstrating that INGN 241 works synergistically with celecoxib (Celebrex) marketed by Pfizer to inhibit the growth and increase apoptosis (cell death) of breast cancer cells.

A team of researchers led by Kelly Hunt, M.D., chief, Surgical Breast Section in the Department of Surgical Oncology at M.D. Anderson Cancer Center, Introgen and the Catholic University of Korea conducted the studies, and the data appear in the current issue of the medical journal Surgery. These data demonstrate the potential utility of INGN 241 in combination with celecoxib, a drug approved for the treatment of pre-cancerous lesions of the colon, and exemplify the increase in understanding of the effects of INGN 241 on multiple cancer-related pathways. Results of this study may help in designing new low-toxicity treatment strategies that combat breast cancer.

Celecoxib is approved by the U.S. Food and Drug Administration (FDA) for the treatment of arthritis and is also approved as the first drug therapy for patients with familial adenomatous polyposis (FAP). FAP is a genetic condition that, if left untreated, almost invariably results in colon cancer.

"The multiple pathways through which INGN 241 exerts its anti-cancer effects support its development as a new cancer treatment that combines the safety and efficacy of a targeted therapy with the broad utility of standard treatment regimens. In this study, we demonstrate the synergistic activity between INGN 241 and celecoxib in killing breast cancer cells. Combining two low toxicity agents may provide additional options for breast cancer patients," said Sunil Chada, Ph.D., Introgen's associate vice president, Clinical Research, and an author on the paper.

Previous studies have shown that celecoxib and INGN 241 work as single agents to inhibit growth and increase killing of cultured breast cancer cells. Celecoxib inhibits COX-2, an important enzyme that is associated with cancer progression and can also regulate the cell survival pathways. Because related cell survival pathways are also a target of mda-7, the active component of INGN 241, studies were undertaken to evaluate the effects of simultaneously inhibiting these pathways in human breast cancer cells.

Results showed that INGN 241, celecoxib and the combination markedly inhibited cell growth compared with controls. The combination of celecoxib and INGN 241 showed greater than additive increases in cell death compared with either therapy alone, and also resulted in the suppression of tumor cell growth. The effectiveness of INGN 241 in combination with celecoxib reported in these studies and the favorable safety profile of INGN 241 observed in clinical trials to date support additional study of this regimen as a novel breast cancer therapy.

The mda-7 gene was discovered by the laboratory of Dr. Paul B. Fisher, professor of clinical pathology at Columbia University. Introgen holds an exclusive worldwide license for all gene therapy applications from the Corixa Corporation. INGN 241 is an investigational cancer therapy currently being evaluated in a Phase 2 study in patients with metastatic melanoma.

A small subset of patients may have increased risk of cardiovascular side effects when taking COX-2 inhibitors like celecoxib. This small risk may be acceptable for cancer patients with unmet medical needs depending upon the potential benefits of celecoxib therapy.

Introgen holds a licensing agreement with M. D. Anderson to commercialize products based on licensed technologies, and has the option to license future technologies under sponsored research agreements. The University of Texas System Board of Regents own stock in Introgen. These arrangements are managed in accordance with M. D. Anderson's conflict of interest policies.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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