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The recent failure of bevacizumab in the adjuvant setting has forced us to consider what has gone wrong. It is possible that with careful analysis and novel biomarkers, we may not yet have to lay bevacizumab to rest.
Hepatocellular carcinoma (HCC) is notoriously resistant to systemic therapies. The success of the anti-VEGF therapy sorafenib in patients with advanced-stage HCC raises hope as well as critical questions on the future development of targeted agents including other antiangiogenic drugs.
The importance of appropriate patient selection necessitates novel clinical trial design and biomarker-driven trials to allow delivery of the right drug to the right patient at the right time—personalized cancer medicine. The WIN Consortium promotes collaboration between critical stakeholders and offers diverse populations of cancer patients the opportunity to participate in clinical trials with new drugs and biologics that target their tumor.
The authors takes a systems-biology approach to the problems of personalized cancer medicine. They describe the challenges of moving to a discipline that is predictive, personalized, preventive and participatory and explore methods for overcoming these obstacles.
New techniques, such as crystallography and three-dimensional modeling, can be used to assist the development of selective targeted agents for cancer treatment. In this Review, Pierotti and colleagues discuss the molecular features of KIT and PDGFRA receptor tyrosine kinases, which are druggable targets in gastrointestinal stromal tumors. The authors focus on the major challenge in kinase drug discovery—the emergence of resistance—and discuss techniques for predicting and preventing this adverse event.
There is an urgent clinical requirement for the detection of early-stage cancer at a time point where curative treatment may be possible. Blood-based biomarkers are likely to be a key component of this detection and of staging and the monitoring of therapy outcomes. To achieve the full potential of these biomarkers international collaborations are required to provide robust, reproducible data that can then be rapidly translated into the clinic.
Modern challenges in oncology, in particular the advent of targeted therapies and personalized medicine, highlight the need for developing a consortium of comprehensive cancer centers to run clinical trials in rare, molecularly-defined populations, and implement high-throughput technologies for daily practice.
Many clinical trials of targeted therapies have produced disappointing results, indicating that many challenges must be addressed to advance this field. The authors discuss the importance of novel statistical designs, the need for biopsy sampling in clinical trials and appropriate biomarker identification for improving treatment outcomes.
Publication bias and hidden multiple hypotheses testing distort the assessment of the true value of biomarkers. The authors of this article propose that a registry should be created for biomarker studies initially focused on studies that use specimens from randomized trials, as a means to alleviate the limitations associated with both publication bias and multiple hypotheses testing.