Drug candidates previewed ahead of ASCO

In the build up to the American Society of Clinical Oncology's (ASCO) annual conference, drug companies from around the world have been showcasing potential drug treatments, with a number of new molecular targets for cancer, writes Wai Lang Chu.

The ASCO conference, which takes place in New Orleans between June 5-8 takes the opportunity to present the best of clinical and translational cancer research. Many drug companies present new drug candidates at the show, and various updates from the ASCO conference will be reported next week.

Just ahead of the start of ASCO, CuraGen and TopoTarget announced a collaboration to develop and commercialise PXD101, a novel histone deacetylase (HDAC) inhibitor for the treatment of solid and hematologic malignancies either as a monotherapy, or in combination with other active anticancer agents.

PXD101 is currently a small molecule candidate in a Phase I clinical trial in patients with advanced solid tumours with CuraGen and TopoTarget planning to initiate a new Phase I trial of PXD101 in patients with hematological malignancies during the summer. In a collaboration with Fujisawa Pharmaceuticals, Gloucester Pharmaceutical company are also involved in research involving HDAC.

Meanwhile, the US governement is to collaborate with Germany's Wilex and the Fox Chase Cancer Centre on a trial of WX-UK1, targeting tumour cell invasion, metastasis, and primary tumour growth. WX-UK1 is a non-cytotoxic small molecule that in animal models blocks tumor cell invasion, metastasis and primary tumor growth by inhibiting the urokinase plasminogen activator (uPA) system.

The open label dose escalation Phase I study will evaluate the safety and biological activity of WX-UK1 in combination with the oral chemotherapeutic agent capecitabine in up to 54 patients with advanced solid tumours.

Oncolytics Biotech has also started a Phase I clinical trial in the UK, investigating the systemic delivery of its reovirus-based drug Reolysin as a treatment for patients with advanced or metastatic solid tumours. The study will involve forty evaluable patients and will depend upon the number of intravenously administered dose levels tested.

Oncolytics' researchers have demonstrated that the reovirus is able to selectively kill cancer cells and, in vitro, kill human cancer cells that are derived from many types of cancer including breast, prostate, pancreatic and brain tumours.

Exelixis has initiated a Phase I clinical trial to evaluate the profile of XL647, an anticancer compound that targets multiple receptor tyrosine kinases (RTKs), implicated in tumor proliferation and vascularisation (angiogenesis). The trial will be conducted in patients with solid tumours for whom there is no alternative therapy. Other drug companies involved in this area of research include the drug major Novartis.

XL647 is the first of several Spectrum Selective Kinase Inhibitors (SSKI) that Exelixis intends to advance into clinical testing. Each SSKI has a different RTK inhibition spectrum, and each has the potential to achieve efficacy through simultaneous inhibition of multiple RTKs. XL647 simultaneously inhibits several growth factors with high potency and demonstrates excellent activity in target-specific cellular functional assays.

Finally, Rexahn, a US biopharmaceutical company, announced plans to initiate its first clinical trial program for the treatment of patients with metastasised cancers.

The Phase I clinical study will be conducted on RX-0201, a first-in-class signal inhibitor that blocks the production of a protein kinase Akt, thereby blocking the proliferation of tumour cells and inducing cell death (apoptosis).Testing is to commence in June 2004 with other companies Keryx Biopharmaceuticals and Astex also involved in Akt research for cancer.