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Personalized Oncogenetics/Oncology

Posted Sep 16 2008 5:45am

In one recent article I’ve found a good summary of research approaches in cancer that lead individualized cancer management (research field –> clinical target):

  • Germline mutation analysis –> Personalized risk assessment and guided prevention
  • Gene expression profiling (multigene assays, gene signatures) –> Prognosis optimization, predictive response to specific therapies
  • Tissue single-gene mutation analysis –> Improvement of predictive precision
  • Circulating tumor cells –> Individual prognosis, fine-tuning
  • Single-nucleotide polymorphism analysis –> Host tailored therapy
  • Cancer stem cells –> Cancer eradication therapy

I could add advances in tumor immunology, especially a better understanding of immune editing and immunosuppressive networks ( T regs etc) as well as monoclonal therapy (see a picture which I’ve added to Wikipedia a couple years ago) and cancer vaccines.

(Update: e.g., VentureBeat presents innovative Bellicum prostate cancer dendritic cells vaccine based on modified CD40 activation.)

First area is quite well established.:

Among these syndromes, HBOC (Hereditary breast ovarian cancer syndrome) and HNPCC / FAP are of the highest clinical significance because a large body of evidence supports the implementation of genetic analysis in clinical intervention strategies in these clinical situations. Indeed, although HBOC accounts for 5–10% of all breast‑-ovarian cancers and HNPCC for 2–4% of colorectal cancers, the high incidence of these tumor types reflect a substantial number of inherited cancers. It is estimated that in the US among 300,000 new annual breast and ovarian cancer cases, approximately 15,000 to 30,000 are attributed to germline BRCA mutations. Similarly among 150,000 colorectal cancer cases approximately 3300 to 6000 are considered to be familial. It is clear that a sensible number of cancer patients could be offered a life-saving early diagnosis, or optimally tumor prevention if genetic screening programs were applied. The development of such strategies could help prevent cancer onset in mutation carriers ( via ).

Gene expression profiling have already entered marked as commercial tests but gene expression studies have widely been criticized for methodology, diversity of genes used and the reproducibility outside highly specialized laboratories. However, despite criticism expressed on the validity of gene sets, a recently published study produced encouraging results by confirming that most gene signature models had high rates of concordance in their outcome predictions for the individual samples [ ref ].

The possible superiority of these tests over standard predictors is assessed in two large randomized prospective trials the TAILORx ( designed by the NCI in the USA) and the MINDACT in the European Union, that are currently recruiting patients with the aim to test the validity of the 21-gene recurrence score (as for Oncotype DX ) and the 70-gene profile (as for Mammaprint ) respectively.

In general it is foreseen by file experts that genomic research will soon be in the position to provide easily applicable versions of gene sets that will give clinicians the opportunity to provide cancer patients a truly personalized treatment ( via ).

Or just simply state - the future is now! I am convinced, that oncology with cancer genetics in front, will be (or already is) the first truly acknowledged personalized medicine practice.

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