Title |
Personalization of cancer treatment using predictive simulation
|
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Published in |
Journal of Translational Medicine, February 2015
|
DOI | 10.1186/s12967-015-0399-y |
Pubmed ID | |
Authors |
Nicole A Doudican, Ansu Kumar, Neeraj Kumar Singh, Prashant R Nair, Deepak A Lala, Kabya Basu, Anay A Talawdekar, Zeba Sultana, Krishna Kumar Tiwari, Anuj Tyagi, Taher Abbasi, Shireen Vali, Ravi Vij, Mark Fiala, Justin King, MaryAnn Perle, Amitabha Mazumder |
Abstract |
BackgroundThe personalization of cancer treatments implies the reconsideration of a one-size-fits-all paradigm. This move has spawned increased use of next generation sequencing to understand mutations and copy number aberrations in cancer cells. Initial personalization successes have been primarily driven by drugs targeting one patient-specific oncogene (e.g., Gleevec, Xalkori, Herceptin). Unfortunately, most cancers include a multitude of aberrations, and the overall impact on cancer signaling and metabolic networks cannot be easily nullified by a single drug.MethodsWe used a novel predictive simulation approach to create an avatar of patient cancer cells using point mutations and copy number aberration data. Simulation avatars of myeloma patients were functionally screened using various molecularly targeted drugs both individually and in combination to identify drugs that are efficacious and synergistic. Repurposing of drugs that are FDA-approved or under clinical study with validated clinical safety and pharmacokinetic data can provide a rapid translational path to the clinic. High-risk multiple myeloma patients were modeled, and the simulation predictions were assessed ex vivo using patient cells.ResultsHere, we present an approach to address the key challenge of interpreting patient profiling genomic signatures into actionable clinical insights to make the personalization of cancer therapy a practical reality. Through the rational design of personalized treatments, our approach also targets multiple patient-relevant pathways to address the emergence of single therapy resistance. Our predictive platform identified drug regimens for four high-risk multiple myeloma patients. The predicted regimes were found to be effective in ex vivo analyses using patient cells.ConclusionsThese multiple validations confirm this approach and methodology for the use of big data to create personalized therapeutics using predictive simulation approaches. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 7 | 41% |
India | 4 | 24% |
Spain | 1 | 6% |
Unknown | 5 | 29% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 10 | 59% |
Scientists | 6 | 35% |
Practitioners (doctors, other healthcare professionals) | 1 | 6% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 2% |
Germany | 1 | 2% |
Canada | 1 | 2% |
Unknown | 59 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 12 | 19% |
Student > Master | 8 | 13% |
Student > Ph. D. Student | 7 | 11% |
Student > Bachelor | 7 | 11% |
Other | 5 | 8% |
Other | 13 | 21% |
Unknown | 10 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 15 | 24% |
Agricultural and Biological Sciences | 9 | 15% |
Biochemistry, Genetics and Molecular Biology | 6 | 10% |
Engineering | 5 | 8% |
Computer Science | 3 | 5% |
Other | 13 | 21% |
Unknown | 11 | 18% |