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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.
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.
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.
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.
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.
A number of biomarkers that predict clinical outcome in response to gemcitabine treatment have been identified. These markers could be used in the clinic to personalize treatment, thereby improving efficacy and reducing adverse effects. The authors of this article describe how treatment can be tailored according to the pharmacogenetics and pharmacokinetics of each patient. In particular, evaluating the status of the liver enzyme cytidine deaminase holds promise as a strategy to optimize therapy.
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.
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.
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.
