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Personalised cancer therapy draws ever closer

By Mike Nagle , 30-May-2007

As more and more targeted drugs enter clinical trials, personalised medicine is fast becoming a reality for cancer sufferers worldwide.

This trend was highlighted at the recent American Association of Cancer Research (AACR) conference where a plethora of molecular targets were discussed. Advances in drug discovery technology and increasing genomic knowledge has led to more companies developing cancer therapies against specific protein targets, rather than more general cytotoxic compounds.


Since these compounds generally have less side effects, the companies are able to gain regulatory approval to enter clinical trials more quickly. The result is that for a given cancer, there is now an extremely complicated picture of which therapies may be effective. Not only that, but the target pathways often overlap, making it even more difficult to choose the best treatment.


According to New Medicine's Oncology KnowledgeBase, among the targets about which preclinical or clinical data was presented at AACR meeting are: Akt (protein kinase B, PKB); Angiopoietin-2; Aurora B (Aurora-1); Bcr-Abl; BRaf (B-Raf); c-Kit; Cyclin-dependent kinase 2 (CDK2); Cyclin-dependent kinase 7 (CDK7); Cyclin-dependent kinase 9 (CDK9); Delta-like 4 (DLL4); Epidermal growth factor (EGFr); focal adhesion kinase (FAK); HEr2/neu; Kinesin-like spindle protein (KSP)/Eg5; c-Kit; Lymphocyte-specific protein tyrosine kinase (Lck); Lyn; Hepatocyte growth factor receptor (HGFr)/c-Met; Notch 1 (TAN1); NF.B; Phosphatase and tensin homolog (PTEN); Phosphatidylinositol 3 kinase (PI3K); Platelet-derived growth factor receptor alpha (PDGFrA); Raf; c-Src; Tie-2; Tumour necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-r2, TRAILr2)/DR5; Vascular endothelial growth factor (VEGF) receptor (VEGFr); VEGFr2/KDR; and VEGFr3/FLT4.


Many of these drugs, based on both small molecules and biologics, are being developed by small biotech companies. As reported by DrugResearcher.com last week , Exelixis have begun more Phase I clinical trials than any other company this year. Another biotech specialising in cancer drugs is ImClone Systems. It develops monoclonal antibodies that target receptors outside the cell and has clinical trials targeting EGFr; PDGFr; IGF1r; VEGFr; and VEGFr2/KDR.


According to data collected by DrugResearcher.com, over 30 different companies have begun clinical development of cancer drugs this year. They range from the relatively small, such as Pharmion Corporation, AEterna Zentaris, Callisto Pharmaceuticals and Array BioPharma, to some of the industy's biggest players in Merck & Co, AstraZeneca and Genentech.


The news comes in the same week as a study in the journal Nature revealed four new genes that appear to raise significantly a woman's risk of getting breast cancer. Scientists from 15 countries conducted the large scale genetic study of nearly 50,000 women, around half of whom had breast cancer and the other half were controls.


Although breast cancer is thought to have a genetic component, until this new research, scientists could only account for around 25 per cent of the genetic part of breast cancer risk. They suspected that the residual genetic variance was likely due to a range of different gene mutations.


In the first of a two stage genome wide association study, 9,000 women were profiled. The scientists then confirmed 30 suspected single nucleotide polymorphisms (SNPs) in nearly 22,000 women with breast cancer and a similar number of controls spanning 22 studies.


Overall, the scientists looked at over 225,000 single nucleotide polymorphisms (SNPs) and identified TNRC9, MAP3K1, LSP1 and FGFR2 as new genes that raise the risk of breast cancer, with the latter appearing to be the most serious indicator.


Douglas Easton of the University of Cambridge, UK, who was involved in the research, said that the discovery could help doctors improve their prediction of breast cancer risk and select better treatments to prevent and cure the disease.


But more important, he said, is how these discoveries help researchers find out how the disease works.


"We had no inkling that these genes had anything to do with breast cancer," he said.


With so many academic groups and companies striving to be the next with a new targeted therapy, the days of one-size-fits-all cancer treatment may be numbered.

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