Reviews & Analysis

Melanoma is the leading cause of death by skin cancer in industrialized countries. Identification of tumor markers may help to define molecular pathways involved in melanoma development and progression, and identify patients with early-stage melanoma who would benefit from additional therapies. Larson et al. overview the melanoma biomarkers that are most helpful for predicting patient outcomes, and discuss the biomarkers that have demonstrated prognostic significance independent of primary tumor thickness and other common clinical prognostic indicators.

Trastuzumab has an established role for the treatment of HER2-positive early-stage breast cancer. The authors of this review discuss the toxicity associated with trastuzumab and the issues associated with determining its optimum timing and schedule, and assert why this agent should be the standard of care in the adjuvant setting.

A choroidal metastasis usually presents as blurred vision or decreased visual acuity and is usually an indicator of poor outcome. The authors describe the case of a 57-year-old woman with a history of breast cancer that presented with distorted vision and decreased visual acuity in her left eye. The authors discuss the use of radiation and hormonal therapy to manage this case of choroidal metastasis from breast carcinoma.

MRI can identify cancer foci that are not evident clinically or detected by mammography. The detection of additional cancer with MRI has been interpreted as evidence that the imaging procedure is beneficial to patients; however, the available data do not support this contention. The author of this Viewpoint discusses why the routine incorporation of MRI into the presurgical workup should not be included for the vast majority of patients with breast cancer.

Epothilones exert their cytotoxicity by stabilizing microtubules dynamics, and have demonstrated a wide range of clinical activity including important anti-tumor effects in advanced prostate cancer. Epothilones have significant activity in patients with prior taxane-treated or taxane-refractory prostate tumors. The authors of this Review summarize the preclinical and clinical data about epothilones and their role in the management of castrate metastatic prostate cancer.

The authors present the case of a 57-year-old male who was diagnosed with grade IV glioblastoma multiforme and enrolled in a clinical trial of adoptive cellular immunotherapy. The authors used PET imaging technology to image the T cells non-invasively and report the first case using a non-invasive imaging reporter gene/probe technology.

For patients with colorectal cancer and liver metastases, hepatic resection is the only potential curable treatment. The role of adjuvant chemotherapy in this setting is still under debate. The authors of this Viewpoint discuss the final results of the EORTC Intergroup randomized phase III study 40983 and whether FOLFOX4 should be the new standard in patients with resectable colorectal cancer and liver metastases.

Despite frequent responses to chemotherapy, curative treatment remains elusive for the majority of metastatic solid tumors. By contrast, chemotherapy routinely cures patients with testicular cancers, gestational choriocarcinoma, Hodgkin's disease and high-grade lymphomas. Savage et al. suggest that the chemo-curability of these malignancies results from an intrinsic 'locked-in' state of sensitivity to pro-apoptotic stresses in these particular cell types, and they discuss some of the characteristics shared by the curable cancers that might explain their curability.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with cancer. Treatment with low-molecular-weight heparin is the recommended first-line approach for treating cancer patients with newly diagnosed VTE. The authors of this Review discuss the optimal duration of anticoagulant therapy, treatment of recurrent VTE, the role of vena cava filters, the effects of VTE and its treatment on quality of life, and the impact of anticoagulants on survival.

Anal mucosal melanoma is a disorder with limited treatment options and is associated with a poor prognosis. The authors describe the case of a 79-year-old man who was diagnosed with stage IV anal mucosal melanoma expressing the KIT Val560Asp mutation, and was treated with surgery, radiotherapy, and a combination of sorafenib and temozolomide therapy. The authors discuss the potential therapeutic use of sorafenib in anal mucosal melanoma patients with specific mutations such as the KIT Val560Asp mutation.

Capecitabine is commonly substituted for conventional 5-fluorouracil chemotherapy based on evidence of the efficacy equivalence of these two drugs and the lack of an increase in overall toxic effects when capecitabine is used. This Review summarizes why there may not be a universally applicable dose for capecitabine because of interpatient differences in basic physiology, pharmacogenomics and diet. The authors also discuss which of these factors contribute to the inter-regional geographical variation in capecitabine toxicity, and the reasons for modifying the starting dose.

Brain metastases are an increasingly prominent problem in the management of women with metastatic breast cancer. Trastuzumab has provided excellent systemic disease control for many patients; however, many women are now living long enough to develop CNS disease. This Review considers the potential for targeted therapy to provide effective management for brain metastases in patients with ErbB2-positive breast cancer, reviewing in particular the data currently available in this setting for lapatinib.

Breast angiosarcoma following surgery and radiotherapy for breast cancer is a rare but important clinical entity. In this Review the authors discuss data collected from over 250 case reports and provide a comprehensive discussion of the incidence, etiology, histopathology, cytogenetics, presentation, diagnosis, prognosis and management of this tumor type.

Cytoreductive nephrectomy has been a standard treatment for patients with metastatic renal cell carcinoma. The introduction of targeted agents has generated interest in using these drugs pre-operatively. The authors discuss the use of molecular targeted therapy and the benefits of cytoreductive nephrectomy.

In the era of personalized, systems-driven medicine, computational orin silicomodeling and the simulation of disease processes is becoming increasingly important for hypothesis generation and data integration in both experiments and clinics alike. The authors of this Review discuss selected studies on modeling malignant brain tumors and the implications for clinical practice, including trial design and outcome prediction.

Although the precise mechanisms by which histone deacetylase inhibitors exert their antitumor activity is not known, certain tumor types undergo a favorable response and consequently several agents have now entered clinical trials. Khan and La Thangue discuss recent developments in our understanding of the molecular events that underlie the anticancer effects of histone deacetylase inhibitors and relate this information to the emerging clinical picture for cutaneous T-cell lymphoma and related malignancies.

Precancerous lesions of the breast have become a considerable clinical problem. It is not always possible to identify which of these lesions will progress to invasive carcinoma, and tailoring the treatment according to each individual case remains a challenge. This Review describes the genetic alterations in these types of lesions, the importance of histological examination for diagnosis, and the most appropriate surgical and radiotherapy management options.

Patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck have a poor prognosis. Cetuximab represents a clinically relevant advance in the treatment of recurrent and metastatic disease. This rationale for cetuximab as monotherapy and its use in combination with platinum-based chemotherapy for recurrent and/or metastatic disease in the first-line setting is discussed.

There have been considerable advances in external-beam delivery and brachytherapy techniques for prostate cancer. Combined-modality therapy with external-beam radiotherapy and brachytherapy is an attractive treatment option for a selected group of patients with clinically localized prostate cancer. Hurwitz discusses the indications for use of combination therapy, choice of low-dose-rate versus high-dose-rate brachytherapy boost, and toxicity and quality of life issues.