Volume 8 Issue 3, March 2011

Imatinib was discontinued in patients with chronic myeloid leukemia (CML) who gained a complete molecular response (CMR). Of those patients with at least 12 months follow-up, 61% experienced recurrence, all of whom responded to rechallenge. The remaining patients maintained CMR, suggesting that imatinib may 'cure' a small proportion of patients with CML.

The outcomes in bladder cancer treated with radiotherapy are suboptimal. Recently, Hoskin et al. reported improved survival in patients with bladder cancer treated with radiation therapy with concurrent hypoxia-modification therapy. These results are promising but must be viewed in the context of previous studies and alternative treatment approaches.

A long-term follow-up study that assessed the effect of daily aspirin on colorectal cancer incidence concluded that it significantly reduced the risk of colon cancer, but not rectal cancer. Detailed analysis of the findings indicate that it is too soon to recommend daily aspirin for cancer prevention in healthy individuals.

ColoPrint^® is an 18-gene expression signature designed to predict disease relapse in patients with early-stage colorectal cancer (CRC). We discuss the potential impact of ColoPrint^® on clinical practice, and its contribution to our knowledge of CRC molecular heterogeneity.

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.

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.

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.

In this Review, Zitvogel and colleagues discuss the impact of immune parameters on the efficacy of chemotherapeutic regimens. They suggest that immune-relevant biomarkers may guide personalized therapeutic interventions including compensatory measures to restore or improve anticancer immune responses.

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.

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.

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.

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.

Nature Reviews Clinical Oncologyis proud to feature a Focus on personalized medicine. The March 2011 special issue features discussions of the advances, challenges and progress in the field of personalized cancer medicine by key opinion leaders who presented at the Worldwide Innovative Networking (WIN) symposium held in Paris in July 2010. Topics include blood-based strategies to detect and monitor cancer, methodological and practical challenges, immune parameters and chemotherapy efficacy, P4 medicine, and personalized medicine perspective from a cancer center. The web page for this focus issue also includes links to related articles from across Nature Publishing Group to provide more background information on this topic.