Reviews & Analysis

Although the epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib can produce dramatic and durable tumor responses, not all patients with non-small-cell lung cancer (NSCLC) benefit from these drugs. This Viewpoint discusses the molecular correlates of response for these agents in patients with NSCLC.

For the treatment of advanced non-small-cell lung cancer, randomized controlled trials have shown that platinum-based chemotherapy and radiotherapy provide a measurable survival benefit compared with radiotherapy alone. Newer drugs that target growth factor receptors might further synergize with ionizing irradiation, although convincing data from multicenter phase III are currently lacking. The authors discuss why concurrent chemoradiation followed by consolidation platinum-based chemotherapy is an attractive approach for treating patients with inoperable tumors.

Recent advances in tumor cytogenetics and molecular biology have clarified that renal-cell carcinoma is not a single entity but comprises a variety of tumors with different histological features, genetic patterns and varying clinical course. Since many cancer molecular markers have been described, this information could help to discriminate aggressive tumors from indolent lesions. The authors describe the benefits of predictive nomograms for improving risk assessment, and discuss the prospects for individual customized follow-up protocols based on tumor molecular characteristics.

The use of central venous catheters (CVC) has improved the management of patients with cancer but this procedure is associated with complications such as infections and upper limb deep-vein thrombosis. This review describes the epidemiology of CVC-related thrombosis and the risk factors associated with this problem. The authors comment on the diagnosis and presentation of CVC-related thrombosis and consider how cancer patients with this complication can be appropriately managed with long-term anticoagulant therapy.

When is chemotherapy too well tolerated? This Viewpoint discusses the possibilities that some patients receive inadequate doses of chemotherapy using the conventional dose calculation method based on body surface area and that a correlation between hematological toxicity and treatment efficacy could be used to titrate therapy.

The myoepithelial cell exerts profound effects on breast tumor cell behavior and resides close to abnormally proliferating breast epithelial cells in precancerous ductal carcinomain situ(DCIS) tumors. These cells also form a natural border separating breast epithelial cells from stromal angiogenesis. Barsky and Karlin discuss the role myoepithelial cells may have in inhibiting the progression of DCIS to invasive breast cancer, and the functional studies that are elucidating the anti-invasive and anti-angiogenic phenotypes of these cells.

Anemia can be a debilitating problem that negatively influences overall quality of life, and it can worsen the prognosis for cancer patients. The requirement for red-blood cell transfusions is reduced in patients receiving erythropoietin therapy. This review discusses quality of life issues, the thromboembolic complications associated with erythropoietin treatment, and provides a critical appraisal of the clinical trial data and evidence-based guidelines for erythropoietin treatment.

Glioblastoma multiforme (GMB) is a devastating neoplasm that nearly always culminates in death within 1–2 years of diagnosis. Despite decades of intensive clinical and laboratory research, progress has been slow, partly because of limited drug delivery and tumor heterogeneity. David Reardon describes an innovative chemoradiation approach that has improved overall survival for newly diagnosed GBM patients, and details a number of promising therapeutic strategies under evaluation.

The Investigational New Drug (IND) process was established to ensure that the FDA is informed of any new treatment before use in humans. The process is now used for approval rather than notification. The time from conception to approval for a new drug is estimated at over 15 years, of which two-thirds is devoted to pre-IND testing. In the meantime the patient is denied access to the investigational treatment. A centralized IND procedure, when the public are already protected by processes within academic centers of excellence, is redundant and costs lives.

Cancer mortality is highest in cancer patients aged 65 years or older. Optimal chemotherapy dosing and regimens for these patients pose a significant challenge because of changes that occur with aging, as well as other comorbidities. This review discusses the important considerations for tailoring chemotherapy to the individual's performance and functional status.

Isolated limb perfusion (ILP) combined with melphalan and TNF-α produces striking response rates for the treatment of bulky melanoma metastases, soft tissue sarcomas and various other tumors. TNF-α-based ILP is a well-established treatment that helps to avoid amputations, and this represents an important approach that is now widely practiced in Europe.

Women withBRCA1/2mutations have a higher risk of breast and ovarian cancer than the general population. The authors outline current evidence for strategies to reduce the risks of cancer development in these women, and discuss future research directions.

In low-resource regions of the world, women with breast cancer often do not present themselves for treatment until the disease has reached an advanced stage. This article offers some cost-effective and practical recommendations for early detection, diagnosis and treatment of breast cancer in low-resource countries.

Bevacizumab with standard chemotherapy improved overall survival in colorectal and lung cancer patients and progression-free survival in breast cancer patients, but this combination failed to increase survival in patients with previously treated and refractory metastatic breast cancer. Reasons for these contrasting results, the mechanisms behind normalization of tumor vasculature for improved drug and oxygen delivery, and the need for biomarkers and imaging techniques to guide patient selection and protocol design are discussed.

The processes of normal and pathological bone biology have been revolutionized since the discovery of the key regulators osteoprotegerin, receptor activator of nuclear factorkappa B (RANK) and RANK ligand (RANKL). Recent research suggests a pivotal role for these molecules in mediating cancer-induced bone destruction. This review provides a comprehensive update on the pathophysiology and mechanisms of skeletal metastasis, and the relevance of therapeutic targeting of these regulators for cancer treatment and pain management.