Review Articles in 2007

Fertility preservation is an important component of cervical cancer treatment, and recently radical surgical procedures have been used in favor of more conservative techniques in an effort to decrease morbidity and preserve fertility without compromising overall survival. The authors of this Review suggest radical vaginal trachelectomy is a safe and feasible procedure in women wishing to preserve fertility, and they review the preoperative considerations, surgical complications and the risk factors associated with this technique.

The methyl binding domain family of proteins have a significant role in controlling gene expressionin vivo, and have been linked to multiple and diverse functions in tumorigenesis. DNA hypermethylation is a well-recognized mechanism underlying gene silencing events in both tumorigenesis and drug resistance. The authors of this review shed light on the mechanisms of this protein family and explain why it is likely that these proteins will be important novel therapeutic targets in the future.

The current tools of clinical risk assessment for medulloblastoma cannot sufficiently identify patients older than 3 years who require aggressive or less-intensive radiation treatment, but considerable effort has been made to improve clinical risk stratification. The current paradigm for stratifying patients for treatment is discussed and the authors highlight that an understanding of the biology of medulloblastoma will help improve clinical risk stratification that currently under treats and over treats a significant percentage of patients.

Single-modality therapy can be used with curative intent for locally confined disease. For the treatment of most solid tumors further improvement is achieved by combining the three standard treatment approaches: surgery, radiotherapy, and chemotherapy. This article reviews the chemoradiotherapy approach to loco-regional treatment with esophageal cancer as the disease focus. The authors present the molecular basis for the enhanced efficacy resulting from the use of concurrent chemoradiotherapy, and discuss how this mechanistic approach can be translated to the clinic.

Although significant advances in primary and secondary cervical cancer prevention have been achieved, their true realization and ultimate impact on global disease outcomes will be affected by a number of complex and interrelated factors. One promising prophylactic HPV vaccine is available and others continue in development as primary cervical cancer prevention strategies in younger women. HPV testing is more sensitive and reproducible than cytology with colposcopy for the detection of precancerous and malignant lesions, and this review presents current advances and perspectives on HPV vaccines and HPV testing.

The successful introduction of genetically engineered human and chimeric immunoglobulin proteins has established monoclonal antibodies as a validated approach for treating malignancies. This review examines the optimal design of these agents, the lessons learned from clinical immunoconjugate development, and the promising agents in early preclinical and clinical development for the treatment of cancer.

It is clear that androgen receptor (AR) expression and signaling remains intact as the disease evolves from androgen sensitive cancer to classically termed hormone-refractory prostate cancer. Genetic and epigenetic changes allow prostate tumors to continue to rely on AR growth signaling and thus remain targets of 'hormonal' therapy. The development of new strategies and new drugs that more effectively abrogate AR signaling will likely result in significant clinical benefits. This article discusses AR structure, function and molecular changes in androgen-independent prostate cancer and reviews novel AR targeting compounds.

The MammoSite^®breast brachytherapy applicator was designed to simplify the brachytherapy procedure and make it more accessible to patients who are suitable candidates for partial-breast irradiation (PBI). Dickler highlights the advantages of this technique such as low rates of serious complications and favorable cosmetic outcome and also summarizes ongoing trials that should provide a definitive answer regarding the benefits of PBI.

Combining cytotoxic drugs with radiation is aimed at improving survival without compromising quality of life. While the current trend in treating epithelial tumors favors concurrent chemoradiation, future regimens should exploit spatial cooperation and temporal modulation mechanisms to optimize the balance between treatment risks and benefits. The authors of this review propose that effective exploration of novel strategies will require a rigorous scientific and mechanistic framework to best identify and test exploitable mechanisms of drug-radiation interaction.

In the first review of this two-part series, Seiwert and co-authors described the rationale for the use of concurrent chemoradiotherapy for treating malignancies. Here the chemoradiotherapy platforms used for the treatment of head and neck cancer are described and the integration of novel agents such as EGFR inhibitors and antiangiogenic drugs into treatment platforms alongside multiagent-based regimens are reviewed. The authors provide guidance for clinicians based on current clinical trial evidence and suggestions for choosing the most appropriate treatment platform.

Schneider and Sledge discuss the mechanisms of resistance associated with anti-angiogenic agents and the problems associated with defining which groups of patients might benefit from this class of therapy. This review highlights the rationale for targeting VEGF and how the combination of anti-angiogenic drugs with other biologic agents is also being explored in clinical trials, in an attempt to improve efficacy and to overcome resistance seen with the initially studied anti-angiogenic drugs.

Concurrent chemoradiotherapy is a highly efficacious locoregional treatment option for solid tumors. The rationale for the use of concurrent chemoradiotherapy for treating malignancies, and the molecular basis for combining classic cytotoxic agents and novel targeted therapies agents with radiotherapy are discussed. This article is part one of two articles. In the subsequent article, the general principles outlined here will be applied to head and neck cancer, where the impact of concurrent chemoradiotherapy is particularly evident.

Health care statistics demonstrate a striking disparity in treatment selection, access, and outcomes between the African-American community and the general population. The role of race and ethnicity in lung cancer etiology is unclear but genetic, cultural and socio-economic factors, in addition to differences in tobacco use and exposure contribute to this disparity. This review summarizes the existing body of knowledge regarding lung carcinoma in African Americans, and identifies promising areas for future investigation and intervention.

Viruses have been used for cancer treatment for over a century. From the early clinical studies with various wild-type viruses, to the modern trials with engineered viruses, virotherapy has emerged as a promising therapeutic strategy. The authors discuss the progress and challenges associated with oncolytic virotherapeutic agents, summarizing the data from clinical reports, and the implications of this data for future virotherapy development.

The presence of tumor cells in the bone marrow of primary breast cancer patients at surgery has been shown to be an independent prognostic indicator of relapse. Studies are underway to improve methods of detection, such as immunobead enrichment and real-time RT-PCR. This article reviews the current methodologies and technical improvements that are being investigated, and the authors discuss the major hurdles that should be overcome before analysis of minimal residual disease to predict prognosis can become standard practice in the clinical setting.

Many women with ovarian cancer undergo both surgery and chemotherapy and because the majority of women will eventually experience recurrent disease, it is important to recognize how such treatments may disrupt patient quality of life. The authors of this review discuss the quality of life issues, and emphasize the importance of developing further strategies to identify women at risk of serious quality of life disruption so that effective interventions can be designed.

Bisphosphonates are used for skeletal protection in osteoporosis, cancer bone metastasis, multiple myeloma, and Paget's disease of the bone; however, these drugs also have the potential for causing a number of adverse effects. While these do not limit bisphosphonate use, the incidence of these adverse events can be minimized if appropriate care is taken with their administration, and by maintaining appropriate surveillance and patient care, as discussed in this review.