Epidermal growth factor receptor (EGFR) signaling inhibition represents a highly promising arena for the application of molecularly targeted cancer therapies. Evolving from several decades of systematic research in cancer cell biology, a series of EGFR inhibitors from both the monoclonal antibody (mAb) and tyrosine kinase inhibitor (TKI) class have been developed and promoted into clinical application. Several EGFR inhibitors have recently gained US Food and Drug Administration approval for cancer therapy in the United States (and many other countries), including the mAbs cetuximab and panitumumab, and the small molecule TKIs gefitinib, erlotinib, and lapatinib. The rapidly expanding preclinical and clinical data contributing to these US Food and Drug Administration drug registrations validates a central role of the EGFR as an important molecular target in epithelial malignancies. In this review, we focus primarily on the biology of EGFR interactions. Through improved understanding of EGFR biology in human cancers, there is anticipation that more tumor-selective therapy approaches with diminished collateral normal tissue toxicity can be advanced. Many questions remain to be answered, particularly with regard to how best combine EGFR inhibitors with conventional cancer therapies, and how to select those patients (tumors) most likely to benefit from EGFR inhibition strategies.

Purpose The purpose of this research was to examine the mediating roles of staff-level employee perceptions of corporate social responsibility (PCSR) and organizational identification in the relationship between transformational leadership and affective organizational commitment. Design/methodology/approach A survey was administered to staff-level employees of private sector companies through social media groups comprising members of the alumni associations of two universities in the northeast of America. A total of 218 responses were received, and the data were analyzed using a serial multiple mediator model. Findings The research indicates that transformational leadership helps staff-level employees perceive the organization as socially considerate, which in turn adds to their feelings of identification and commitment to the organization. Perceived corporate social responsibility and organizational identification do mediate the relationship between transformational leadership and affective organizational commitment. Leader development programs should consider emphasizing transformational leadership to achieve a win for both organizations and society. Originality/value This study adds empirical evidence to understand the linkage between transformational leadership and PCSR in staff-level employees. The research provides insight into how leaders can be responsive to stakeholder demands through transformational leadership, how PCSR is engendered at the staff-level, how staff-level employee PCSR contributes organizational value and how PSCR and organizational identification partly explain how transformational leadership effects affective organizational commitment.

Signaling through the insulin-like growth factor-I receptor (IGF-IR) is implicated in cellular proliferation, apoptosis, carcinogenesis, metastasis, and resistance to cytotoxic cancer therapies. Targeted disruption of IGF-IR signaling combined with cytotoxic therapy may therefore yield improved anticancer efficacy over conventional treatments alone. In this study, a fully human anti-IGF-IR monoclonal antibody A12 (ImClone Systems, Inc., New York, NY) is examined as an adjunct to radiation therapy. IGF-IR expression is shown for a diverse cohort of cell lines, whereas targeted IGF-IR blockade by A12 inhibits IGF-IR phosphorylation and activation of the downstream effectors Akt and mitogen-activated protein kinase. Anchorage-dependent proliferation and xenograft growth is inhibited by A12 in a dose-dependent manner, particularly for non-small cell lung cancer lines. Clonogenic radiation survival of H226 and H460 cells grown under anchoragedependent conditions is impaired by A12, demonstrating a radiation dose-enhancing effect for IGF-IR blockade. Postradiation anchorage-independent colony formation is inhibited by A12 in A549 and H460 cells. In the H460 xenograft model, combining A12 and radiation significantly enhances antitumor efficacy compared with either modality alone. These effects may be mediated by promotion of radiationinduced, double-stranded DNA damage and apoptosis as observed in cell culture. In summary, these results validate IGF-IR signal transduction blockade as a promising strategy to improve radiation therapy efficacy in human tumors, forming a basis for future clinical trials. [Cancer Res 2007;67(3):1155-62]

Depending on initial prognostic factors, an estimated 10%-60% of men who undergo definitive radiation therapy for prostate cancer may experience a biochemical recurrence. Even though hormonal therapy is standard for metastatic recurrences, no consensus exists on optimal salvage therapy for those recurrences thought confined to the prostate. Salvage treatment options for these local recurrences have historically been limited to salvage prostatectomy, hormonal therapy, or cryotherapy. Salvage prostate brachytherapy, however, uses a widely available technique and may provide another option for attaining disease control in patients with localized failures, although only about 110 cases have been reported in the literature. In this report, the authors have described their own series of salvage brachytherapy cases as well as presented a review of other such series reported in the literature. In addition, the authors included a comprehensive review of published experiences with surgery and cryotherapy as salvage options. It appears that salvage brachytherapy, when combined with careful patient selection, is at least as effective as other salvage options with comparable or potentially fewer treatment-related side effects.

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