Reviews & Analysis

Advances in the fields of genetics and gene-expression profiling and the advent of microarray technology have revolutionized the concept of patient tailored treatment. Before microarrays qualify as a useful clinical tool, however, they must demonstrate reliability and reproducibility. Limitations of microarray technology include sample acquisition and methods of biostatistical analysis required to analyze the enormous quantities of data obtained. Abdullah-Sayaniet al.overview the current status of microarray technology in clinical practice and propose how advances in this technology will help eliminate some of these limitations and improve patient management.

Developing chemotherapeutic regimens that can be given at the optimal dose and schedule continues to be one of the greatest challenges in clinical oncology. Simon and Norton discuss how they used guiding principles to derive the Norton–Simon hypothesis, and describe how this has improved clinical trial design and helped to achieve the goal of more effective and less toxic chemotherapeutic regimens.

As more aggressive cytotoxic agents and targeted therapies become the standard treatment approach in oncology, tumor lysis syndrome (TLS) will be more frequently encountered. Not only should the metabolic abnormalities of acute TLS and its complications be treated, but it is critical for prevention that patients at risk are identified as early as possible. This review discusses the symptoms and clinical features of this syndrome and the authors highlight the issues related to appropriate monitoring of treatment and the use of prophylaxis.

The oncogene addition concept was established to explain how some cancers that contain multiple genetic, epigenetic, and chromosomal abnormalities are dependent on or are “addicted” to one or more genes for both maintenance of the malignant phenotype and cell survival. Weinstein and Joe summarize current experimental and clinical evidence of this concept and describe some of the molecular mechanisms of this phenomenon. The use of molecular targeted agents in combination with cytotoxic agents, and the advances in systems biology and network theory can help to facilitate an optimal treatment approach.

The incidence of male breast cancer is rising, and the treatment of this disease has been extrapolated from the knowledge of female breast cancer despite multiple differences in the pathogenesis, biology and genetics of these two disease entities. Although there have been major advances in hormonal manipulation for the treatment of breast cancer, an improved understanding of the potential differences between male and female breast cancer is essential to providing new opportunities for therapeutic intervention and likely improved outcome, as discussed in this review.

Early treatment of pancreatic cancer increases the likelihood of survival, but detection of the disease is difficult in the early stages. The authors of this Viewpoint recommend screening populations at increased risk of developing pancreatic cancer because of family history, to identify early disease in a higher proportion of patients.

Despite recent progress in oncology, the continuing high incidence and mortality rates illustrate that our overall approach to tackling this disease is still inadequate. While the emphasis on treatment of end-stage disease is crucial, chemoprevention approaches could be regarded as the 'Cinderella' of the cancer field; largely neglected from cancer research and practice. This review elaborates on fundamental dichotomies in our outlook between traditional and revisionist viewpoints and presents a new synthesis, which builds on old strengths but also encourages a holistic approach to the entire cancer problem aimed at improving quality of life.

Regulation of cell death pathways is pivotal to cancer development and progression. Much knowledge has been gained from basic research efforts to understand the complex molecular mechanisms that drive cell turnover, leading to several strategies that modulate the cell death machinery. This article discusses these strategies, which include development of epigenetic modifiers of gene expression, gene therapy approaches, and compounds that induce pro-apoptotic events, and overviews the recent progress on some of these strategies that are being explored and tested in clinical trials.

Bortezomib is a protease inhibitor and is the first compound in this drug class to be used in clinical practice, with trials demonstrating efficacy in patients with relapsed/refractory multiple myeloma. Mature clinical data on the efficacy of bortezomib in solid tumors are not yet available, but early clinical data indicate this could be a promising drug for the treatment of advanced solid tumors. This Review summarizes the principal clinical trials of bortezomib and discusses its efficacy in solid and hematologic tumors.

The effectiveness of renal cryoablation is difficult to determine in the absence of specific clinical research protocols, and the role of this technique in the treatment of small renal masses cannot yet be defined as a paradigm shift.

Hemopoietic stem-cell transplantation (HSCT) remains an important curative therapy for many malignant and non-malignant conditions and its use worldwide is increasing. Although many advances have been made in this field, graft-versus-host disease (GvHD), or its treatment, is responsible for causing high morbidity and mortality in patients potentially cured from their primary disease. This review summarizes the successful treatment of steroid refractory-dependent acute and chronic GvHD with extracorporeal photochemotherapy.

Locoregional techniques have become the mainstay of therapy for patients with unresectable hepatocellular carcinoma (HCC). These include catheter-based approaches and locoregional ablative techniques. These therapies are mainly utilized for palliation, but have also been used with curative intent. This review outlines the current status of the most commonly used image-guided loco-regional interventions for the treatment of HCC, and describes recent research and advances related to image-guided interventions for HCC.

There is extensive in vitro and in vivo preclinical evidence that bisphosphonates, particularly zoledronic acid and ibandronate, have antitumor activity, can reduce skeletal tumor burden, and might potentially have antitumor activity outside the bone microenviroment. The authors of this review highlight the importance of correct sequencing of these compounds when used in conjunction with cytotoxic drugs, targeted molecular therapies, and radiotherapy. The need to identify new molecular targets of nitrogen-containing bisphosphonates is discussed in this context and the correct sequence and the timing of drug administration could help drive molecular research and determine the efficacy of the therapy, both in advanced disease and in the adjuvant setting.

No single indicator provides unambiguous information regarding the population burden and dynamics of breast cancer. Milena Sant and co-authors discuss the trends in incidence, survival and mortality for patients with breast cancer in Western Europe and suggest a strategy for analysis of these data.

Several randomized trials have demonstrated improved survival rates and local control when concurrent cisplatin-based chemotherapy was added to radiation therapy in patients with locoregionally advanced cervical cancer. Randomized trials that investigated the administration of neoadjuvant chemotherapy before radiation therapy, however, have failed to demonstrate a benefit of this approach. Based on clinical trial evidence cisplatin-based chemoradiation should be considered a standard treatment for most patients with locoregionally advanced carcinoma of the cervix who do not have medical contraindications to this aggressive treatment.

Despite the impressive results seen in phase II trials of trastuzumab, many tumors that overexpress HER2 show resistance to the drug. Understanding the molecular mechanisms underlying primary or treatment-induced trastuzumab resistance is critical to improving the survival of patients with metastatic breast cancer with aggressive HER2 overexpressing tumors. This review discusses the novel therapeutic strategies that target the aberrant molecular pathways, and explains how these strategies could greatly improve the duration of response to trastuzumab.