Review Articles in 2008

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.

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.

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.

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.

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.

Cardiovascular disease in patients with cancer and cardiac complications of cancer therapy is an increasing clinical problem. Optimum management of cardiovascular disease can allow patients with cancer to successfully receive cancer therapies and it can reduce morbidity and mortality caused by cardiovascular disease in cancer survivors. The authors of this review discuss management strategies for cardiovascular disease in patients with cancer, focusing on the prevention and treatment of congestive heart failure and myocardial infarction.

Five adjuvant breast cancer trials have clearly demonstrated the benefit of trastuzumab in reducing the recurrence rate and mortality in patients with aggressive HER2-positive disease. The controversies and challenges relating to the use of trastuzumab in the adjuvant setting, such as the optimal timing and duration, its use with taxanes and radiotherapy, its role in small node-negative tumors and cost-effectiveness are discussed.

The current method for assessing response to therapy of glial tumors is based on the Macdonald et al. criteria; however, these criteria are ambiguous in key features such as the appropriate threshold for lesion size and the actual methods for applying the stated criteria. The authors of this Review identify the strengths and shortcomings of the current approach and also discuss technological advances in both drug therapy and imaging that necessitate reassessment of the Macdonald et al. criteria.

Technologies such as mass spectrometry, and protein and DNA arrays, have enabled simultaneous examination of thousands of proteins and genes, giving opportunities to identify distinguishing signatures for cancer diagnosis and classification and prediction of therapeutic response. The authors provide an overview of how the current cancer biomarkers were discovered and their associated limitations, discuss the utilization of these emerging technologies, and review their potential to revolutionize biomarker discovery.

Our understanding of the biology of Hodgkin's lymphoma has improved, in particular the genetic and phenotypic characteristics of malignant cells and the signaling pathways involved in the pathogenesis of this disease. While newer regimens have improved the cure rates of patients with Hodgkin's lymphoma, some are associated with severe acute and long-term toxicities. This comprehensive Review discusses combined modality regimens for treating early-stage disease, approaches used for treating advanced disease and other novel regimens.

In epithelial ovarian cancer, gene-expression profiling has been used to provide prognostic information, to predict response to first-line platinum-based chemotherapy, and to discriminate between different histologic subtypes. The authors of this Review summarize the contributions of gene-expression profiling to the diagnosis and management of epithelial ovarian cancer and discuss ways in which this technique could become a useful tool in clinical management.

Our understanding of the pathogenesis of tobacco-related lung carcinogenesis is improving but the molecular mechanisms of neoplastic transformation in never-smokers have not yet been elucidated. Mountzios et al. describe the best characterized signaling pathways that are implicated in the transduction of proliferative signals, and discuss the differences in the molecular characteristics of smokers and never-smokers.