Reviews & Analysis

The use of altered fractionation radiotherapy in conjunction with chemotherapy-enhanced radiotherapy has been investigated in an attempt to improve the prognosis of patients with advanced-stage head and neck squamous cell carcinoma (HNSCC). The advantages and long-term complications of this approach are described, and the importance of treatment compliance and the enhancement of local-regional control for management of patients with locally advanced HNSCC are discussed, together with approaches to optimize concurrent radiotherapy and chemotherapy.

Members of the signal transducers and activators of transcription (STAT) pathway have recently been demonstrated to have a major role in cancer. Constitutive activation of the STAT family members Stat3 and Stat5, and/or loss of Stat1 signaling, is found in a large group of diverse tumors. STAT proteins can regulate many pathways important in oncogenesis including cell-cycle progression, apoptosis, tumor angiogenesis, and tumor-cell evasion of the immune system. This review highlights STAT signaling pathways, STAT target genes involved in cancer, evidence for STAT activation in human cancers, and therapeutic strategies to target STAT molecules for anticancer therapy.

Recent scientific advances have provided new insights into why leukemia is such a difficult disease to treat and identified molecular processes activated in leukemia stem cells that may facilitate their drug resistance and quiescent cell-cycle status. Monoclonal antibody therapy may be appropriate for malignant cells, and other approaches involve identification and targeting of specific survival pathways for these biologically distinct cells, which are discussed in this Viewpoint article.

Prostate cancer is one of the leading causes of cancer death in the US, making it an attractive target for chemoprevention. Androgens are known to promote prostate cancer, and compounds that inhibit their production, such as 5α-reductase are promising chemopreventive agents. Other potential strategies to reduce prostate cancer initiation include limitation of inflammation, which is associated with prostate cancer onset. The authors elegantly describe the mechanisms by which COX2 inhibitors, NSAIDs, selenium and vitamin E have been linked to prostate cancer prevention.

Understanding the tumor microenvironment and bone marrow interactions for multiple myeloma is crucial for the development of new therapies aimed at circumventing resistance to conventional therapy. Kumar and Anderson discuss how the development of thalidomide and its immunomodulatory derivatives are a milestone in the treatment of this disease, and how assessment of these agents in model systems has shown great promise in the clinic, thereby paving the way for the development of even more effective therapies.

In order to improve prognostic and predictive markers of breast cancer, assessment of formalin-fixed paraffin-embedded tissue is important. However, there are problems associated with the use of paraffin-embedded tissue for gene-expression profiling, especially when analyzing older samples. Paiket al. discuss the advantages of using real-time reverse transcription-polymerase chain reaction (RT-PCR) for gene-expression level quantification and describe how the Oncotype DX™ RT-PCR assay, among others, has helped to circumvent some of these challenges.

International consensus has not yet been reached for the use of preoperative chemotherapy for localized esophageal cancer. Chong and Cunningham give an overview of the latest trials and meta-analyses, discussing possible reasons for discrepant findings, and giving their interpretation of best clinical practice for this disease.

Intensity-modulated radiation therapy (IMRT) has advantages over standard radiotherapy techniques, but few studies have been performed in pediatric cancer patients, and as a result radiation oncologists have not universally accepted its use. This review discusses the current and future applications of IMRT in pediatric malignancies and its potential pitfalls, and highlights the radiotherapeutic options available for pediatric patients unsuitable for conventional radiotherapy.

Recent improvements in the development of antiemetics have helped to minimize chemotherapy-induced nausea and vomiting. Oo and Hesketh review the latest clinical trial data and discuss how the introduction of two new antiemetics, palonosetron, a 5-HT3 antagonist, and aprepitant, a NK-1 antagonist, have demonstrated significant advances for patients inadequately controlled with conventional antiemetic regimens.

Discovery of molecular pathways critical to carcinogenesis is revolutionizing the treatment and prevention of cancer. This review discusses recent advances in colorectal cancer chemoprevention and the development of novel anti-inflammatory agents that target signaling pathways important in tumor formation and metastasis, such as those involving cyclooxygenase (COX1 and COX2) and the epidermal growth factor receptor (EGFR).

This Viewpoint advocates a radical rehaul of the system for describing breast pathology, to echo the classification systems used in other organs. Molecular alterations detected by comparative genomic hybridization highlight some of the deficiencies of the current system for differentiation of different types of breast tumors.

Histone deacetylase inhibitors show significant activity against a broad spectrum of neoplasms, at doses that are well tolerated by cancer patients. These molecules control post-translational modification of histones, which is an important epigenetic regulation of gene expression. The discovery and development of suberoylanilide hydroxamic acid (SAHA), which is one of the most advanced compounds in this group, is the focus of this review.

Quality-of-life improvements and nutritional status are important in the management of cancer patients, but are often overlooked. Treatments for anorexia and cachexia are often attempted during the advanced stages of the disease. Cytokines and tumor-derived factors appear have a significant role in the pathogenesis of anorexia and cachexia. Laviano et al. discuss the pathogenesis and diagnosis of cachexia and anorexia, focusing on the dietary and drug interventions, which can prolong survival and positively influence quality of life for cancer patients.

Epstein–Barr virus (EBV)-associated malignancies are a heterogenous group of tumors that are generally relatively radiosensitive and chemosensitive in their early stages, but less amenable to conventional modality therapy in late stage or relapse. New and emerging strategies to manipulate the immune response are discussed. These strategies are used either alone or as an adjuvant therapy in combination with chemotherapy with or without monoclonal antibodies.

Diagnostic improvements and earlier detection of tumors have resulted in the emergence of a shift from Halsted paradigm, which has encouraged the use of systemic adjuvant therapy. With these changes in tumor paradigm, the rationale for local treatment as a curative treatment strategy has been challenged. This Viewpoint emphasizes the importance of local control in this scenario.

While the potential for therapeutic cancer vaccines has been recognized, based on modest clinical trials in the metastatic setting, a gap exists between the limited clinical activity of cancer vaccines and promising preclinical findings. Morseet al. discuss the relevance of appropriate platforms for cancer vaccine testing, identification of the most important biologic endpoints, and reiterate the need to improve our understanding of how to manipulate the immune system beyond the initial vaccine-induced stimulation. The authors focus on the areas of cancer vaccine development that will translate into clinical application.

The function ofHelicobacter pyloriin inflammation-induced gastric cancers is one of the best studied infectious etiologies. A better understanding of the molecular mechanisms underpinning this process, and the role of inflammation in malignancies seen in other organs where inflammation is common, will lead to novel cancer prevention and treatment strategies for gastric cancers and other malignancies.