Antisense Therapeutics trial of ATL1101 in prostate cancer shows promise

Jun 18 2009

Antisense Therapeutics Ltd. (ASX: ANP) has reported further positive results from its collaborative preclinical research studies on the therapeutic potential of ATL1101 in prostate cancer. In experimental models, ATL1101 treatment significantly enhanced the tumor-suppressive effect of the cancer drug Paclitaxel. Paclitaxel is one of a class of drugs known as taxanes.

Along with androgen (a male hormone) blockade, taxane chemotherapy is an important treatment option in the most dangerous form of the disease, castration-resistant prostate cancer (CRPC).

Illustrating the positive effects of the drug in this mouse model of prostate cancer, prostate tumor volume was halved after 5 weeks of Paclitaxel/ATL1101 combination treatment, compared with control Paclitaxel treated mice.

In cell culture experiments, the amount of Paclitaxel required to induce tumor cell apoptosis (cell death) was significantly reduced when used in combination with ATL1101. This ability to 'sensitize' tumor cells to the cytotoxic effects of Paclitaxel affirms ATL1101's potential as a chemo-sensitizing agent to be used in combination with existing prostate treatments to improve the outcomes for patients.

ATL1101 is a second generation antisense inhibitor of the insulin-like growth factor-I receptor (IGF-IR) which as reported previously suppressed the growth of human prostate tumors in an animal model of prostate cancer, and slowed down transition to CRPC when used as a single agent. Drugs targeting IGF-IR are being developed by a number of the major pharmaceutical companies for a variety of cancer indications, indicating the importance of the IGF-IR target in cancer.

ANP's research collaborator in the study is Prof. Martin Gleave, a leader in prostate cancer treatment and drug development. Martin Gleave, a professor at the Department of Urological Sciences, University of British Columbia and Director of The Prostate Centre at Vancouver General Hospital commented, "Resistance of tumor cells to the effects of existing treatment is a major challenge in the management of prostate cancer. Tumor cells build resistance to chemotherapy treatment via survival mechanisms that include IGF-I signaling. In our prostate cancer model we have shown that ATL1101, which is an IGF-I receptor blocker, can inhibit this mechanism and restore sensitivity to chemotherapy."

ANP is in dialogue with various parties regarding the continued development of ATL1101 in prostate cancer, aiming to build on ATL1101's robust pre-clinical pharmacology data package, completed mouse toxicology study, established drug manufacturing process and strong intellectual property protection.