Reviews & Analysis

Bevacizumab, sorafenib, sunitinib and temsirolimus have been approved for use in patients with advanced solid cancers. Many other drugs with activity in preclinical models, however, have failed to show efficacy in clinical trials. The authors of this Review describe the studies that led to the approval of these antiangiogenic agents, discuss the potential value of biomarkers of angiogenesis, and provide rationale for future developments.

Many drugs are used to treat colorectal cancer but there is little information about how predictive factors can be used to improve treatment response and reduce toxic effects related to anticancer treatment. The authors of this Review analyse the main data in this investigation field, and highlight the most important predictive factors that relate to toxic effects in patients with colorectal cancer who are treated with anticancer chemotherapy, both in adjuvant and in advanced setting.

Until recently, the standard of care for the treatment of glioblastoma involved surgical resection followed by radiation therapy with or without nitrosourea-based chemotherapy. In 2005, a large trial established adjuvant temozolomide chemotherapy and radiotherapy as a new standard therapy. This Review summarizes new developments in the treatment of glioblastoma and speculates on possible future treatment strategies for managing this aggressive cancer.

Brain tumors may harbor small subpopulations of cells that share characteristics of neural stem cells. The use of neural stem cells and progenitor cells as delivery vehicles of molecules toxic to tumors offers a promising experimental treatment strategy. This Review summarizes recent advances in the basic understanding of neural stem cell and cancer-stem-cell biology and the progress towards translating these novel concepts into the clinic.

Estrogen-receptor expression is a useful predictive marker of response to endocrine therapy in patients with breast cancer. The authors of this Viewpoint discuss the use of gene-expression profiles and predictive markers for determining the optimum treatment strategy for women with breast cancer.

More-effective systemic therapies are needed for colorectal cancer, and particularly for metastatic disease, for which median survival rates remain below 2 years. The addition of panitumumab to best supportive care has improved efficacy in patients with chemotherapy-refractory metastatic disease, and is associated with a favorable safety profile. The authors discuss the available data and ongoing investigations of this agent in the first-line and second-line settings.

Patients treated with irradiation for Hodgkin's lymphoma are at increased risk of breast cancer. Alm El-Din et al. report the case of a 57-year-old woman who was diagnosed with breast cancer 15 years after receiving mantle irradiation for Hodgkin's lymphoma and was managed with lumpectomy and partial breast irradiation. The authors suggest partial breast irradiation as a feasible approach for women who develop breast cancer after Hodgkin's lymphoma and decline mastectomy.

Although many studies have investigated the associations between stress-related psychosocial factors and cancer outcomes, the results have been inconclusive. The authors of this Review use meta-analytical methods from 165 studies to determine if there is an association, and discuss the results indicating that stress-related psychosocial factors have an adverse effect on cancer incidence and survival.

Spinal radiosurgery was developed to overcome the limitations associated with invasive surgery and traditional radiotherapetuic approaches for the treatment of these lesions. The authors of this Review discuss the benefits of this new therapeutic technique, such as low rate of complications, durable pain relief and local tumor control while maintaining physical and mental quality of life.

Specific biological markers that reliably predict unfavorable outcome during first-line treatment for patients with Hodgkin lymphoma are lacking. Recent analyses have shown that differences in hematotoxicity exist among male and female Hodgkin lymphoma patients, with a better prognosis observed in female patients. Klimm and Engert discuss the reasons for these differences in hematotoxicity and how these differences relate to patient outcome.

Although cancer is a preventable disease, few medical interventions are completely without risk or adverse effects. It is critical to establish a framework to determine when interventions show sufficient promise of efficacy and sufficient safety to justify their testing in clinical trials. This Review identifies the issues that are critical for decision making and provides a framework that can be applied in making these decisions.

Proteus syndrome is a rare hamartoma syndrome that is characterized by the presence of germlinePTEN mutations and causes benign and malignant tumors. Marsh et al. report the case of a 16-month boy who was diagnosed with Proteus syndrome, and was managed with oral rapamycin. On the basis of this patient's promising outcome, the authors discuss the rationale for rapamycin therapy for patients with disorders within the PTENhamartoma tumor syndrome spectrum.

Cancer stem cells often represent a minor, highly self-renewing population within the tumor mass and are thought to be the only cells required for both initiation and maintenance of disease. The biology of cancer stem cells, the mechanisms of therapy resistance, and potential future therapeutic interventions in the clinical setting are discussed.

The incidence of breast cancer in the US dropped sharply between 2002 and 2003. In this Viewpoint, the author discusses two theories to account for this observation: the decrease in use of hormone-replacement therapy and a decline in the US screening mammography rates.

Allogeneic non-myeloablative stem-cell transplantation is feasible for patients with various refractory and advanced solid tumors. Current data suggest that the graft-versus-tumor effect associated with this approach might prolong survival of some patients with metastatic solid tumors. The authors discuss the latest results from the literature and recent data from the European Bone Marrow Transplantation Solid Tumors Working Party.

Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for the majority of patients with high-risk or advanced hematologic malignancies. Schöttker et al. describe the case of a male patient with acute lymphoblastic leukemia who received cord-blood, third-party CD34⁺stem-cell, and T-cell transplantation after experiencing primary graft failure. The authors discuss the therapeutic potential of this combined non-HLA restricted transplantation for patients with hematologic disorders.

Cardiotoxicity is a rare but serious complication of the management of breast cancer, and adjuvant trastuzumab after anthracycline chemotherapy increases congestive heart failure risk. The authors review the efficacy of trastuzumab, its potential for cardiac compromise, and its interaction with anthracyclines. The biological mechanisms that might be responsible for cardiotoxicity are highlighted, and the clinical strategies used to minimize the risk of developing cardiac failure are discussed.

Several toxicities are associated with molecular-targeted drugs including gastrointestinal adverse effects. These adverse effects need to be considered carefully because they can lead to the discontinuation of oral treatment and subsequently compromise cancer control. The authors of this Review discuss the incidence and clinical patterns of the gastrointestinal toxic effects induced by these agents and propose some hypotheses for each adverse event.

Epithelial–mesenchymal transition (EMT) is a phenotypic conversion that facilitates organ morphogenesis and tissue remodeling. The authors of this Review discuss the phenomenon of EMT in relation to tumor development, and the function of EMT in promoting invasion and metastasis. The roles of ERK1, ERK2 and PI3-kinase, as microenvironmental responsive regulators of EMT are also highlighted.

Gastrointestinal stromal tumors that metastasize cannot be controlled by systemic chemotherapy or radiotherapy; however, tumor control in such patients can be achieved with imatinib. The author of this Viewpoint discusses whether imatinib should be used as adjuvant therapy in patients who are at risk for developing metastasis, and whether tumor size is an appropriate criterion for such therapy.