Review Articles in 2009

Members of the nuclear receptor superfamily of transcription factors have been implicated in a broad range of normal physiological and disease processes. There is evidence in support of the involvement of these co-regulators in breast cancer progression. The authors review the role of steroid receptor coactivator-3, which is frequently amplified in breast cancer, and discuss its role in breast cancer risk, outcome and response to endocrine therapy in patients with breast cancer.

Trastuzumab and lapatinib improve survival in patients with HER2-positive breast cancer and there is great interest in developing diagnostic tests that predict which patients are more likely to benefit from specific HER2-directed therapies. This article discusses the predictive role ofHER2mRNA, predictive markers for response to therapy and the mechanisms for overcoming resistance in metastatic disease.

There has been extensive research evaluating the clinical usefulness of genomic biomarkers. High-throughput genomic technologies have revolutionized genomic research but challenges in biomarker assessment include clinical study design, reproducibility and interpretation of results. This Review explores these challenges, focusing on microarray-based gene-expression profiling, and highlights some common failings in study design that have impacted on the clinical use of putative genomic markers.

It has been established that intraperitoneal drug administration is advantageous in patients with tumors confined to the peritoneal cavity. The authors of this Review discuss intraperitoneal drug delivery including the optimal drug, dose and schedule.

Important innovations have been achieved in the development of novel systemic hormonal therapies for the salvage treatment of metastatic castrate-resistant disease. The use of chemotherapy as an adjunct for the treatment of castrate-resistant metastatic disease and local advanced tumors has also resulted in patterns of late toxic effects. The authors review the important advances in the evolution of systemic therapy for the treatment of prostate cancer.

Taxanes are among the most widely used chemotherapy agents for breast cancer. The results of the first-generation taxane trials are reviewed and the authors discuss the possible explanations for the differences observed in these studies. The inclusion criteria for future clinical trials of adjuvant taxane therapy must be revised to account for the molecular heterogeneity of breast cancer.

Stereotactic body radiation therapy has emerged as a novel cancer therapy in the past 10–15 years This review article gives an overview of the background, radiobiologic, technical and clinical aspects of stereotactic body radiation therapy.

Microarray studies have been used to unravel the molecular characteristics of breast cancer and a molecular taxonomy has been proposed. The authors of this Review discuss the origins of the diversity of breast cancer and, based on the study of histological special types of breast cancer, propose an approach for the identification of novel therapeutic targets.

Radiotherapy is one of the most important and effective therapies used to treat cancer. Particle therapy is an emerging technique and there is debate surrounding its cost-effectiveness. The authors of this Review present clinical results in the field and discuss the research questions that have arisen with this technique.

Six European randomized controlled trials that will compare human papillomavirus (HPV) testing with cytology testing for cervical screening are under way. The outcome of HPV testing versus cytology testing depends not only on the relative accuracy of the primary test but also on how radical the different triage procedures are. Two trials have shown a 50% reduction in grade 3 cervical intraepithelial neoplasia detection in subsequent screening rounds. The authors critically discuss the reasons for the different results observed in these trials and the implications for primary screening.

Gamma-delta lymphomas are rare and aggressive lymphomas with a poor prognosis. The authors of this Review discuss the clinical and biological features of the two types of such lymphomas and the diagnostic challenges associated with these still insufficiently known diseases.

Most patients with advanced colorectal cancer die from hepatic metastases. Radioembolization is a technique for administering radiotherapy internally to unresectable primary or secondary hepatic malignancies in a single procedure to improve local control of disease. This technique enables significant downsizing of liver metastases after surgical resection, and the rationale for this approach combined with cytotoxic and molecularly targeted agents is outlined.

Some lymphoma entities are associated with chronic bacterial infections. This Review discusses the association betweenChlamydophila psittaci and ocular adnexal lymphoma. Prevalence, epidemiology and detection methods of C. psittaciinfection along with therapeutic implications in ocular adnexal lymphoma are also discussed.

This Review discusses the criteria for the diagnosis and classification of myeloproliferative neoplasms in relation to the revised 2008 WHO classification. The authors summarize the histology of these tumors in the context of the 2008 WHO classification system, discuss associated cytogenetic and molecular abnormalcies of myeloproliferative neoplasms, and provide diagnostic algorithms that are tailored for routine clinical use.

After resection, malignant gliomas are routinely treated with adjuvant radiotherapy and temozolomide. The efficacy of these therapies has led to an increasing incidence of pseudoprogression and radiation necrosis, treatment-related effects that resemble tumor progression or recurrence on gadolinium-contrast MRI. The authors of this Review discuss the prognostic importance of accurate diagnosis of these post-treatment lesions, and the use of advanced imaging modalities for this purpose.

Src family kinases have been extensively studied and found to be central mediators in multiple signaling pathways that are important in oncogenesis. Preclinical studies have shown that SFK inhibitors can suppress tumor growth and metastases. The authors of this Review discuss the potential use of these agents to target cancer in humans.

Cyclophosphamide is one of the most widely utilized chemotherapeutic and immunosuppressive agents in many combination chemotherapy regimens and autoimmune conditions. This Review highlights the chemistry, pharmacology, clinical toxic effects and current clinical applications of cyclophosphamide in cancer and autoimmune disorders. It also discusses the development of high-dose cyclophosphamide for blood and marrow transplantation and the treatment of autoimmune diseases.

The VEGFR small-molecule inhibitors of angiogenesis show promise for oncology patients. These rationally designed inhibitors are being tailored for use in specific malignancies and will have a pivotal role in personalized medicine. The authors discuss the potential of these agents for treating tumors such as metastatic renal-cell carcinoma, GIST and hepatocellular carcinoma.

With the development of new chemotherapy and targeted agents, neurotoxicity has become increasingly important as a cause of dose-limiting toxicity. The authors review the important and unusual neurotoxicities related to chemotherapy and targeted agents approved since January 1999.

With greater understanding of the biology of pancreatic cancer a role for cancer stem cells is becoming clear. The authors of this Review discuss the current knowledge on pancreatic cancer stem cells and their potential use as targets in therapeutic regimens.