In the US, like much of the developed world, cancer is the second most common cause of death after cardiovascular disease. Together between 1970 and 1994, Lung, Colon, Breast, Prostate and Pancreatic cancers claimed more than 5 million lives in the US alone. Considering these statistics and the often sub-optimal treatment options, it is unsurprising that anti-cancer drugs have received more attention from the pharmaceutical industry than any other drugs. Cancer is characterized by uncontrolled proliferation and in most cases reduced apoptosis. Despite the attractiveness of proapoptotic strategies and the level of research focussing on the development of such drugs clinical progress has been disappointing to date and the search for new targets is intense. One such target is the CLN3 gene product. This gene was originally identified in 1995 following studies showing that it's mutation was responsible for the juvenile form of the neurodegenerative disorder ceroid lipofuscinosis (Batten disease). CLN3 was found to suppress the production of the apoptotic molecule ceramide and consequently mutations in CLN3 contribute to the increased ceramide levels and apoptosis observed in Battens disease. More recently however, the therapeutic implications of CLN3 have been dramatically broadened with mRNA and protein levels having been shown to be increased in prostate, ovarian, breast and colon cancer as well as in glioblastoma, neuroblastoma. This suggests that CLN3 contributes to the suppression of apoptosis under conditions of neoplastic progression. More importantly blockade of CLN3 through antisense technology causes elevation in endogenous ceramide production through de novo ceramide synthesis and results in increased apoptosis, inhibiting the growth and viability of cancer cells. This new data suggests that CLN3 could represent a novel target for the future treatment of at least three of the major forms of cancer.

The CLN3 Gene is a Novel Molecular Target for Cancer Drug Discovery. Rylova et al, Cancer Res 2002 Feb 1;62(3):801-8

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk