Review Articles in 2010

The validation of predictive and prognostic biomarkers and surrogate end points requires robust statistical analysis of data gathered from multiple, large, independent studies. In this Review, Marc Buyse and coauthors discuss this validation process and the nature of biomarkers and surrogate end points. Furthermore, they consider strategies for the pragmatic evaluation of biomarkers and surrogate end points in the absence of statistical validation.

The first generation of anti-cancer agents using novel nanomaterials has successfully entered widespread use and newer nanomaterials are gaining increasing interest as potential multifunctional therapeutic agents. The authors of this Review discuss how the new features of these agents could potentially allow increased cancer selectivity, changes in pharmacokinetics, amplification of cytotoxic effects, and simultaneous imaging capabilities.

Rapid advances in techniques such as DNA sequencing and genome-wide-association studies have made a great impact on oncology research. In this comprehensive Review, the authors describe some of the most important molecular changes in different cancers that have been gleaned from these technologies, and have allowed earlier diagnosis and more appropriate treatment. The authors also highlight why the molecular pathology revolution is profound for cancer patients and the health-care system.

Painful bone metastases can be treated with radiotherapy, and single-fraction radiotherapy with 1 × 8 Gy has been shown to be as effective for pain relief as multi-fraction regimens. The authors discuss why single-fraction radiotherapy is considered the standard regimen for uncomplicated painful bone metastases without pathological fractures or spinal cord compression, and highlight the reasons why long-course multi-fraction radiotherapy should be reserved for patients with a relatively favorable survival prognosis.

Mammalian target of rapamycin (mTOR) has a key role in several pathways that are involved in cell growth and cancer. In this Review, Dr. Dancey outlines the mechanisms of action and performance of current mTOR inhibitors in clinical trials. Second-generation inhibitors are also discussed along with strategies that should be used to improve outcomes achieved with mTOR inhibitors.

Surgery of esophageal cancer is associated with a poor prognosis, yet there is no international consensus on the optimal management of operable esophageal cancer. The authors of this Review discuss the role of perioperative chemotherapy and definitive chemoradiation, and the associated survival benefits.

Mutations in the mismatch repair (MMR) genes are associated with an increased risk of developing colorectal cancer (CRC). In this Review, the authors outline the MMR system and describe how defective MMR impacts on the management of CRC. The authors also discuss how targeting these mutations can be exploited in the development of novel therapeutic strategies.

Melanoma is an increasing problem, especially in the elderly population. In this article, the authors highlight key aspects of the epidemiology, presentation, staging and management of melanoma. They also emphasize the need for greater understanding and awareness of this cancer to optimize patient outcomes.

Microsatellite instability (MSI) is a frequent molecular phenomenon of colorectal cancer and is associated with deficient DNA mismatch repair. This Review presents an overview of MSI, including its clinical features and applications. The authors discuss the prognostic and predictive value of MSI and how it can be used to improve our knowledge of other cancer subtypes.

Breast cancer is a heterogeneous disease with different molecular drivers regulating its growth, survival and treatment response. Drug development efforts have resulted in agents against new molecular targets that are active against only those tumors with the targeted molecular alteration or phenotype. The authors critically discuss the recently established and investigational strategies for the treatment of the main breast cancer subtypes.

Pancreatic adenocarcinoma is the most lethal of the solid tumors and most patients present with locally advanced or metastatic disease that precludes curative resection. Considerable efforts have been made during the past decade to identify better systemic treatments. The authors of this Review discuss the current standards of care for patients with locally advanced and metastatic pancreatic carcinoma, and outline future directions for the development of new treatment strategies.