Review Articles in 2011

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.

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.

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.

The translation of mRNA is a tightly regulated process that is necessary for protein synthesis, and dysregulation of this process is associated with the development and progression of cancers. This Review highlights the components of translation machinery and how alterations in these proteins and their principle upstream signaling pathways can impact on cancer. Drugs that are currently being developed to target the translational machinery are also discussed.

The progression-free survival benefits from approved antiangiogenic drugs are modest and are frequently not accompanied by overall survival improvements. Recent disappointing clinical trial results (for example AVANT) have highlighted questions about the basis of drug resistance, the limitations of predictive preclinical models, and whether antiangiogenic therapy may lead to more invasive or metastatic tumor behavior.

For the treatment of early-stage breast cancer, a provocative question is whether some patients can safely be spared chemotherapy? This Review addresses this question by discussing a range of clinicopathological, biomarker and genomic techniques that may help to guide current clinical practice.

KRASrepresents the first biomarker to be integrated in clinical practice for the treatment of colorectal cancer. However, clinical study design, reproducibility, interpretation and reporting of the clinical data remain important challenges. This Review highlights the clinical application of published prognostic and predictive protein and genomic markers and the possibilities offered by novel adaptive clinical trial designs.

PET–CT is important for the staging of disease, but also in detecting mechanisms of resistance at the molecular level. In combination with tracers, these imaging modalities can delineate the underlying processes of resistance, such as tumor-cell proliferation, hypoxia, and vascular density. The authors of this Review discuss how the use of various tracers makes it possible to predict outcome and monitor response to treatment. By selecting patients on the basis of their mechanism of resistance, it should be possible to avoid the rejection of treatment options by assessing individuals rather than a population as a whole.

Advances in the understanding of the molecular pathology of the two types of endometrial carcinoma have underpinned the first steps in the development and testing of targeted therapies. This Review discusses the therapeutic targets, molecular diversity of tumors, oncogene addiction and synthetic lethality in this hard-to-treat disease.