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AS1411 has shown activity against a wide range of solid and blood cancer cell lines in preclinical experiments and could therefore have potential against a variety of human cancers. Initial clinical development is focused on one blood cancer, AML (acute myeloid leukaemia) and one solid tumour, renal cancer (kidney cancer or renal cell carcinoma). A phase II clinical trial is ongoing in AML and a phase II trial is planned in renal cancer.

A previous phase I trial of AS1411 in 30 patients with various advanced cancers reported no serious adverse events related to treatment. Promising signs of anti-cancer activity were seen among patients in the trial with renal cancer (see below).

AS1411 is an aptamer. This is a type of drug based on a short piece of DNA or RNA. However, unlike some other drugs based on these chemicals, aptamers work as conventional drugs, binding to a protein target by virtue of a fit with its three-dimensional structure. The term aptamer is derived from the Greek ‘aptos’ (to fit).

AS1411 has a structure that allows it to bind specifically to a protein called nucleolin, which is found on the surface of many cancer cells. One bound, the AS1411 aptamer is taken into the cancer cell, where it causes death by apoptosis (programmed cell death).

AML (acute myeloid leukaemia)

Studies have shown that blast cells from patients with AML are highly sensitive to AS1411, while normal B cells are unaffected by high doses of the drug. AML cell lines are also very sensitive to AS1411, and synergy (more than additive effects) have been seen when AS1411 is combined with cytarabine (Ara-C), a common current treatment for AML. A randomised phase II trial is evaluating the addition of AS1411 to cytarabine.

Renal cancer

In the phase I trial of AS1411 there were 12 patients with advanced renal cancer. Promising signs of anti-tumour activity were seen in this group, including two objective responses with substantial tumour shrinkage. In addition to these clinical findings, renal cancer cell lines have shown high sensitivity to AS1411. We are planning a phase II trial with AS1411 in renal cancer .