PIK3CA gene mutations found in brain cancers
cancers, could lead to the development of targeted molecular
therapeutics, controlling brain cancer development through
regulation of the errant gene.
The discovery could also opens the door to screening processes that can identify patients for treatment strategies as well as becoming a useful diagnostic marker.
Scientists have discovered that the gene PIK3CA encodes a specific signalling enzyme, or kinase, that is vulnerable to a variety of mutations found in five types of brain cancers.
Protein kinase genes are known to play key roles in cellular processes including cell division, signal transduction, apoptosis and cell mobility. They have been the focus of recent drug development strategies, with some tumour-inhibiting compounds such as Gleevec, which is a protein kinase inhibitor already in use clinically to thwart tumour growth.
Dr Hai Yan, the senior scientist of the study told DrugResearcher.com: "Mutations in the gene PIK3CA occur spontaneously as part of the brain tumour development rather than being passed genetically between generations."
"Mutations in PIK3CA, a member of the family of PI3Ks catalytic subunits, were identified in a significant fraction (25-30 per cent) of colorectal cancers, gastric cancers, and in a smaller fraction of breast and lung cancers."
Yan and colleagues pinpointed a cluster of 13 mutations on two particular areas of the PIK3CA gene, exons 9 and 20. The mutations were identified in different types of brain tumours. 14 per cent of anaplastic oligodendrogliomas, 5 per cent of medulloblastomas, 5 per cent of glioblastomas and 3 per cent of anaplastic astrocytomas.
Yan added: "The consistency of hot spot mutations in PIK3CA across diverse tumour types suggests a possible approach to targeted therapy to develop agents acting as highly selective antagonists of the mutant alleles products, sparing normal cells exhibiting wild-type PIK3CA activity."
While Yan wouldn't be drawn on the commercial aspect at this stage, he did say more studies needed to be carried out to investigate the functions of the abnormal gene product and its potential as a specific target of cancer therapeutics.
A total of 30,000 new cases per year of primary malignant and benign brain tumours are diagnosed in the United States. Brain tumours constitute a heterogeneous group of diseases that vary from benign, slow-growing lesions to aggressive malignancies that can cause death within a matter of months if left untreated.
In addition to surgery, therapy includes irradiation, chemotherapy, or treatment with investigational approaches. New therapy is sorely needed to reduce toxicity and increase the efficacy.
Protein Kinases, as a drug target to fight cancer, promise much in terms of effectiveness and pharmaceutical efficacy. Protein kinase inhibitors (PKI) target kinases and kinase signalling pathways and many of the major drug companies are in the process of launching PKI drugs.
Chiron's Angiozyme, OSI's Tarceva, and Aventis' Flavopiridol demonstrated synergistic effects for many of these agents when combined with either chemotherapy or radiotherapy, leading to great enthusiasm regarding their ultimate contribution to cancer therapy. In order to be fully efficient, several PKI often have to be used in combinatory treatment regimes.
