Comparative Effectiveness Research, Genomics-Enabled Personalized Medicine, and Rapid Learning Health Care: A Common Bond.
ABSTRACT Despite stunning advances in our understanding of the genetics and the molecular basis for cancer, many patients with cancer are not yet receiving therapy tailored specifically to their tumor biology. The translation of these advances into clinical practice has been hindered, in part, by the lack of evidence for biomarkers supporting the personalized medicine approach. Most stakeholders agree that the translation of biomarkers into clinical care requires evidence of clinical utility. The highest level of evidence comes from randomized controlled clinical trials (RCTs). However, in many instances, there may be no RCTs that are feasible for assessing the clinical utility of potentially valuable genomic biomarkers. In the absence of RCTs, evidence generation will require well-designed cohort studies for comparative effectiveness research (CER) that link detailed clinical information to tumor biology and genomic data. CER also uses systematic reviews, evidence-quality appraisal, and health outcomes research to provide a methodologic framework for assessing biologic patient subgroups. Rapid learning health care (RLHC) is a model in which diverse data are made available, ideally in a robust and real-time fashion, potentially facilitating CER and personalized medicine. Nonetheless, to realize the full potential of personalized care using RLHC requires advances in CER and biostatistics methodology and the development of interoperable informatics systems, which has been recognized by the National Cancer Institute's program for CER and personalized medicine. The integration of CER methodology and genomics linked to RLHC should enhance, expedite, and expand the evidence generation required for fully realizing personalized cancer care.
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ABSTRACT: Drug resistance mechanisms in renal cell carcinoma (RCC) still remain elusive. Although most patients initially respond to targeted therapy, acquired resistance can still develop eventually. Most of the patients suffer from intrinsic (genetic) resistance as well, suggest-ing that there is substantial need to broaden our knowledge in the field of RCC genetics. As molecular abnormalities occur for various reasons, ranging from single nucleotide poly-morphisms to large chromosomal defects, conducting whole-genome association studies using high-throughput techniques seems inevitable. In principle, data obtained via genome-wide research should be continued and performed on a large scale for the purposes of drug development and identification of biological pathways underlying cancerogenesis. Genetic alterations are mostly unique for each histological RCC subtype. According to recently pub-lished data, RCC is a highly heterogeneous tumor. In this paper, the authors discuss the following: (1) current state-of-the-art knowledge on the potential biomarkers of RCC sub-types; (2) significant obstacles encountered in the translational research on RCC; and (3) recent molecular findings that may have a crucial impact on future therapeutic approaches.Frontiers in Oncology 07/2014; 4(194).
- Journal of Clinical Oncology 05/2014; · 17.88 Impact Factor
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ABSTRACT: The emerging paradigm of Precision Oncology 3.0 uses panomics and sophisticated methods of statistical reverse engineering to hypothesize the putative networks that drive a given patient's tumour, and to attack these drivers with combinations of targeted therapies. Here, we review a paradigm termed Rapid Learning Precision Oncology wherein every treatment event is considered as a probe that simultaneously treats the patient and provides an opportunity to validate and refine the models on which the treatment decisions are based. Implementation of Rapid Learning Precision Oncology requires overcoming a host of challenges that include developing analytical tools, capturing the information from each patient encounter and rapidly extrapolating it to other patients, coordinating many patient encounters to efficiently search for effective treatments, and overcoming economic, social and structural impediments, such as obtaining access to, and reimbursement for, investigational drugs.Nature Reviews Clinical Oncology 01/2014; · 15.03 Impact Factor