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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.
The use of whole-brain radiation therapy (WBRT) in the treatment of primary central nervous system lymphoma is controversial. A recent randomized study addressing the use of this therapy was flawed and questions remain about the use of WBRT in these patients.
Mediastinal staging of patients with lung cancer is used to avoid futile thoracotomies. Endoscopic, esophageal and bronchial ultrasound procedures are methods to identify involved lymph nodes. The ASTER study indicates that the sensitivity of these new techniques is high, reducing the number of futile thoracotomies and improving outcomes when combined with mediastinoscopy.
The high attrition rate for cancer drugs is discussed in this Review of the preclinical models available to cancer researchers and clinicians. The classic methods of drug discovery and analysis are described along with new preclinical strategies, including the genetically engineered mouse models and small-interfering RNA that have identified promising targeted drugs. Better knowledge of oncogenic signaling pathways and the mechanism of action of their inhibitors is probably the most effective way to improve the development of successful anticancer drugs.
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.
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.
In this Perspective, the clinical disappointment of mitosis-specific agents is explained in the context of the mechanism of action of microtubule-targeting agents. The authors propose a new paradigm for the anticancer activity of microtubule-targeting agents and suggest that mitosis-specific inhibitors will not result in significant clinical impact.
