Antisense drug demonstrates anti-tumour activity
Antisense inhibition of the drug target Signal Transducer and Activator of Transcription 3 (STAT-3), a protein that regulates cell division and growth, and prevents cell death, significantly delayed tumour growth and increased the rate of cancer cell death in multiple cell and animal models of cancer, according to data presented at Advances in Cancer Therapies 2004 meeting in London.
Antisense inhibition of the drug target Signal Transducer and Activator of Transcription 3 (STAT-3), a protein that regulates cell division and growth, and prevents cell death, significantly delayed tumour growth and increased the rate of cancer cell death in multiple cell and animal models of cancer, according to data presented at Advances in Cancer Therapies 2004 meeting in London.
ISIS 345794 is a second-generation antisense drug that targets STAT-3, and based on these pre-clinical findings, Californian-based Isis Pharmaceuticals has selected ISIS 345794 for clinical develop-ment. Dr Nicholas Dean, Isis vice president, Functional Genomics commented: 'STAT-3 is a com-pelling drug target in oncology as it is expressed and activated in a wide range of solid and haematological cancers, such as prostate, breast, lymphomas and multiple myeloma. There is a substantial amount of scientific data which demonstrate that activation of STAT-3 initiates a series of cellular events that eventually lead to malignancy.
'In our study, we observed that selective, dose-dependent inhibition of this target produces pro-apoptotic effects while slowing the rate of tumour growth, potentially delaying the progression of the disease for cancer patients. We intend to rapidly move ISIS 345794 into clinical development, and anticipate initiating clinical trials in patients with cancer in 2005.'
About STAT-3
STAT-3 is a member of a multi-gene family called Signal Transducers and Activators of Transcription, which is involved in the regulation of cell growth. STAT-3 appears to play an important role in cell development and death, and is active in a wide range of cancers, including both solid and haematological cancers. Activated STAT-3 is present in numerous malignancies including head, neck, prostate, breast and lung cancers, and in multiple myeloma, anaplastic lymphoma, chronic myeloid leukaemia and melanoma. The control of both the activation and inactivation of STAT-3 is equally important to maintain normal cell growth.