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Biomedical subjects

Paul Harari

Publications and source records attributed to Paul Harari.

3 recordsLinked to original sources

Targeting epidermal growth factor receptor signaling in the treatment of head and neck cancer.

In this review, key aspects of epidermal growth factor receptor (EGFR) biology and the fruitful translation of these fundamental findings into recent treatment advances in head and neck squamous cell cancer (HNSCC) are highlighted. In contrast to a number of contemporary reviews of the EGFR, many of which focus on colorectal and nonsmall cell lung cancer, this review discusses the EGFR as a validated therapeutic target in HNSCC. Recent data confirm a survival advantage for the addition of the anti-EGFR monoclonal antibody cetuximab to definitive radiation therapy in locoregionally advanced HNSCC patients, as well as palliative benefits for patients with incurable recurrent and metastatic HNSCC. Small-molecule EGFR tyrosine kinase inhibitors also show considerable promise in this disease, both alone and in combination with radiation and chemotherapy. Both classes of anti-EGFR agent are generally well tolerated, with side effects (notably skin rash) that are distinct from the toxicities of conventional chemotherapy. Ongoing clinical trials will more clearly define the role for EGFR inhibitors in all treatment phases of HNSCC.

Drug Delivery Systems↗

Image guidance for precise conformal radiotherapy.

PURPOSE: To review the state of the art in image-guided precision conformal radiotherapy and to describe how helical tomotherapy compares with the image-guided practices being developed for conventional radiotherapy. MATERIALS AND METHODS: Image guidance is beginning to be the fundamental basis for radiotherapy planning, delivery, and verification. Radiotherapy planning requires more precision in the extension and localization of disease. When greater precision is not possible, conformal avoidance methodology may be indicated whereby the margin of disease extension is generous, except where sensitive normal tissues exist. Radiotherapy delivery requires better precision in the definition of treatment volume, on a daily basis if necessary. Helical tomotherapy has been designed to use CT imaging technology to plan, deliver, and verify that the delivery has been carried out as planned. The image-guided processes of helical tomotherapy that enable this goal are described. RESULTS: Examples of the results of helical tomotherapy processes for image-guided intensity-modulated radiotherapy are presented. These processes include megavoltage CT acquisition, automated segmentation of CT images, dose reconstruction using the CT image set, deformable registration of CT images, and reoptimization. CONCLUSIONS: Image-guided precision conformal radiotherapy can be used as a tool to treat the tumor yet spare critical structures. Helical tomotherapy has been designed from the ground up as an integrated image-guided intensity-modulated radiotherapy system and allows new verification processes based on megavoltage CT images to be implemented.

Animals↗

Interference with EGFR signaling: paradigm for improving radiation response in cancer treatment.

The introduction of biologically active agents that interfere with the epidermal growth factor receptor (EGFR) provides a promising opportunity to improve cancer treatment outcomes. Several EGFR-selective agents, such as humanized monoclonal antibodies and small molecule, orally available tyrosine kinase inhibitors have shown antitumor activity in early clinical trials in advanced cancer patients. Preclinical studies have demonstrated enhanced radiation- and chemotherapy-induced tumor cytotoxicity when EGFR antagonists are implemented. More broadly, recent clinical trials have confirmed improved survival with combinations of HER-2 (a member of the ErbB family of receptors) targeted antibodies and chemotherapy in patients with advanced breast cancer. A landmark trial combining C225 antiEGFR antibody with radiation therapy for patients with locally advanced head and neck cancer has just completed accrual. Thus, emerging rapidly are cancer treatment strategies based on an improved understanding of the specific cellular and molecular abnormalities of individual tumors.

Animals↗