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Mathis et al. aimed to determine the effect of multimodality therapy on recurrence and survival in patients with locally advanced colorectal cancer. Use of multimodality treatment led to excellent local control with five year disease-free and overall survival rates comparable to that of stage-matched resectable colorectal cancers.
On the basis of the results of KRAS analysis from the CO.17 randomized, controlled, phase III study by Karapetis et al., KRAS mutations have emerged as a valid predictive marker associated with resistance to cetuximab and lack of survival benefit from this anti-EGFR antibody in patients with chemoresistant colorectal cancer.
A randomized phase III trial evaluated the effect of adding lapatinib to paclitaxel as first-line therapy for patients with metastatic breast cancer whose tumors were negative or untested for human epidermal growth factor receptor 2 (HER2) overexpression. Progression-free survival was prolonged significantly in patients with HER2-overexpressing tumors, which indicates that lapatinib exerts its main effects via the HER2 pathway.
The association of a treatment-related adverse effect with treatment success has been reported in various clinical situations. The development of vasomotor or joint symptoms is an indication of therapeutic benefit in women receiving endocrine treatment for hormone-receptor-positive breast cancer.
Targeted therapies offer new hope in overcoming the challenges encountered with conventional chemotherapy. However, little is known about the precise mechanisms that cause resistance. These issues are discussed in light of data from the BRiTE study, which indicate that the antiangiogenic effects of bevacizumab might persist despite the development of resistance to first-line chemotherapy.
Treatment interruptions during radiotherapy may have a negative effect on patient outcome. D'Ambrosio et al. demonstrated that prolonging treatment duration has an adverse effect in low-risk patients with prostate cancer. Thus, limiting or modifying the overall elapsed time between treatments is necessary.
Although VEGF-targeted anti-angiogenic agents have proved successful, resistance to these targeted therapies remains a challenge. Therefore, additional angiogenesis inhibitors are being developed to overcome resistance. Carmeliet et al. discuss the molecules implicated in conferring resistance to VEGF-targeted therapy, and describe how targeting non-endothelial mechanisms in the tumor stroma may offer opportunities to overcome resistance to VEGF-targeted therapy.
No validated biomarkers currently exist for appropriately selecting cancer patients for antiangiogenic therapy. A number of potential systemic, circulating, tissue and imaging biomarkers have emerged as suitable candidate biomarkers, but all require prospective validation. The authors discuss the current challenges in establishing biomarkers, the advantages and disadvantages of systemic, circulating, tissue and imaging biomarkers, and the future opportunities for validating biomarkers of antiangiogenic therapy.
The molecular characterization of disseminated tumor cells and circulating tumor cells opens a new avenue for understanding cancer dormancy and might contribute to the identification of metastatic stem cells with important implications for future therapies. This Review focuses on the clinical relevance of the latest research results on blood-borne cancer micrometastasis in patients with cancer.
The authors summarize the literature and present an overview of the fast-moving field of anti-EGFR therapeutics for the treatment of non-small-cell lung cancer. They focus on describing the effects of somaticEGFRmutations in selection of patients for treatment with tyrosine kinase inhibitors and the influence of EGFR pathway regulation.
Breast cancer during pregnancy is increasingly being encountered, and establishing the safety of trastuzumab in this setting is important. The case of a 29-year-old woman diagnosed with node-positive, HER2-positive breast cancer is described. She underwent surgery followed by chemotherapy and radiotherapy and then received trastuzumab. The authors suggest that short-term trastuzumab exposure may be safe and they recommend careful monitoring of the amniotic fluid and cardiac assessment of the mother and fetus.
