Novel Akt Inhibitor VQD-002 Shown to Reverse Cisplatin Resistance in Ovarian Cancer
Cisplatin is a chemotherapeutic agent used to treat a range of cancers including ovarian cancer. In the study, a specific microRNA (miRNA) known as miR-214 was shown to induce cancer cell survival and cisplatin resistance through activation of the Akt pathway, an important regulator of cell proliferation and survival. Based on these findings, researchers conclude that miRNA molecules play a critical role in inducing treatment resistance and disease progression in ovarian cancer. Inhibition of the Akt pathway following the introduction of VQD-002 was shown to sharply reduce miR-214-induced ovarian cancer cell survival.
"VQD-002's distinct mechanism of action coupled with encouraging pre-clinical and clinical data strongly support our plan to advance this product candidate into Phase II trials in 2008," said Michael D. Becker, president and chief executive officer of VioQuest Pharmaceuticals.
The study results reported by investigators from the H. Lee Moffitt Cancer Center and Research Institute show that miR-214 and several other miRNAs are altered in human ovarian cancer cells. In this altered state, miR-214 induces cell survival and cisplatin resistance primarily by activating the Akt pathway.
"MiR-214 is frequently deregulated in ovarian cancer as well as in other types of human tumors. By disrupting the ability of altered miR-214 to activate the Akt pathway, VQD-002 could potentially become an effective strategy to stop the process that leads to drug resistance and thereby improve patient outcomes," said Jin Q. Cheng, M.D., Ph.D., professor of molecular oncology at H. Lee Moffitt Cancer Research Center.
VQD-002 has also shown promise in efforts to address treatment resistance for patients with breast cancer treated with Herceptin(R) (trastuzumab). In pre-clinical study results presented in the peer-reviewed publication Clinical Cancer Research in October 2007, trastuzumab in combination with VQD-002 was shown to inhibit cell growth and induce cell death in breast cancer cells that were previously trastuzumab resistant.
"The issue of drug resistance in breast cancer affects thousands of patients each year. In research involving breast, ovarian, and other cancers, VQD-002 has proved to be highly effective in targeting the specific pathway associated with treatment resistance involving some of the most widely-used therapeutic agents available to patients today," Mr. Becker added.
About VQD-002
VQD-002 (triciribine phosphate monohydrate, or TCN-P), a tricyclic nucleoside that inhibits the phosphorylation of Akt, has demonstrated anti-tumor activity against a wide spectrum of cancers in preclinical and clinical studies. Amplification, overexpression, or activation of Akt, also named protein kinase B, have been detected in a number of human malignancies, including prostate, breast, ovarian, colorectal, pancreatic, and hematologic cancers. Activation of Akt is associated with cell survival, malignant transformation, tumor invasiveness, and chemo-resistance, while inhibition of Akt activity has been shown to cause cell death. These attributes make Akt an attractive target for cancer therapy.
About Ovarian Cancer
The American Cancer Society estimates that about 22,430 new cases of ovarian cancer were diagnosed in the United States during 2007 and that the disease leads to approximately 15,000 deaths each year in the United States. The majority of ovarian cancer patients are diagnosed with late stage disease where the cancer has spread beyond the ovary. The prognosis is poor in these patients, leading to the high mortality from this disease. Current drug therapy typically involves paclitaxel and carboplatin/cisplatin regimens. Many patients develop resistance to these drugs, so there is substantial need for innovative therapies that can overcome resistance.
About VioQuest Pharmaceuticals
VioQuest is a New Jersey-based biotechnology company dedicated to becoming a recognized leader in the successful development of novel drug therapies targeting both the molecular basis of cancer and side effects of treatment. VioQuest's oncology portfolio includes: VQD-002 (triciribine phosphate monohydrate), a targeted inhibitor of Akt phosphorylation, which is currently being tested in Phase I clinical trials in both solid and hematological malignancies; Lenocta(TM) (sodium stibogluconate), an inhibitor of certain protein tyrosine phosphatases such as SHP-1, SHP-2, and PTP1B, which is currently in a Phase IIa trial for solid tumors; and Xyfid(TM) (1% topical uracil), which is expected to enter Phase II development in 2008 for the treatment and prevention of Hand-Foot Syndrome, a common side effect from certain chemotherapy treatments.
Further information about VioQuest can be found at www.vioquestpharm.com.
This press release contains forward-looking statements that involve risks and uncertainties that could cause VioQuest's actual results and experiences to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These forward-looking statements concern the timing, progress and results of the clinical development, regulatory processes, potential clinical trial initiations of VioQuest's product candidates, as well as the potential role these product candidates may play in the treatment of cancers. These statements are often, but not always, made through the use of words or phrases such as anticipates, expects, plans, believes, intends, and similar words or phrases. These statements are based on current expectations, forecasts and assumptions that are subject to risks and uncertainties, which could cause actual outcomes and results to differ materially from these statements. These statements are subject to various risks and uncertainties and include VioQuest's need for additional capital to fund its clinical development programs, the possibility that the results of clinical trials will not support VioQuest's claims, the possibility that VioQuest's development efforts relating to its product candidates will not be successful, the inability to obtain regulatory approval of VioQuest's product candidates, VioQuest's reliance on third-party researchers to develop its product candidates, its lack of experience in developing and commercializing pharmaceutical products, and the possibility that its licenses to develop and commercialize its product candidates may be terminated. Additional risks are described in VioQuest's Annual Report on Form 10-KSB for the year ended December 31, 2006. VioQuest assumes no obligation and does not intend to update these forward-looking statements, except as required by law.
Herceptin(R) is a registered trademark of Genentech.
Posted: January 2008
