R Perez-Soler

..Other uses are being tested, such as imatinib for gastrointestinal stromal tumor. These compounds will alter cancer care as adjuncts to currently available treatment options...

..The cause of the possible relationship between rash and clinical benefit remains unclear at this time, and additional studies are needed to determine the clinical utility of this observation...

..Although there are still significant challenges to implementing genomic and proteomic testing in clinical practice, the rapid development of newer technologies provides hope for overcoming these barriers...

..The increasing use of HER1/EGFR-targeted agents makes managing rash important. We hope the outcomes from this Forum provide background for future studies...

..We hypothesized that phosphatase inhibition in the skin keratinocytes may prevent receptor dephosphorylation caused by EGFR inhibitors and be used as a new potential strategy for the prevention or treatment of this side effect...

..It is important to remember that intracellular targeting of HER is a relatively novel approach, and our knowledge of how best to optimize such treatment is still unfolding. More clinical experience is needed...

..Clinical studies addressing these five areas are ongoing and are briefly described in this review...

..This phase II study of erlotinib in patients with HER1/EGFR-expressing non-small-cell lung cancer previously treated with platinum-based chemotherapy evaluated tumor response, survival, and symptom improvement...

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..Erlotinib is active and well tolerated in patients with NSCLC as first- and second-line therapy. Cutaneous rash appears to be a surrogate marker of clinical benefit, but this finding needs to be confirmed in ongoing and future studies...

..Rational treatments based on the biological mechanisms of the skin toxicity must be developed and tested in well-controlled clinical trials...

..NSCLC heterotransplants deserve to be explored to evaluate new agents for lung cancer and to predict clinical response on an individual basis in selected groups of patients...

..We studied the combination of these two novel biologic agents in vitro using a panel of non-small cell lung cancer cell lines...

..In this study, we examined whether inhibition of EGFR N-glycosylation and stimulation of endoplasmic reticulum (ER) stress by tunicamycin enhances erlotinib-induced growth inhibition in NSCLC cell lines...

..A priori screening of colon tumors for PTEN expression status and PIK3CA and Ras/BRAF mutation status could help stratify patients likely to benefit from this therapy...

..Taken together, these results suggest that erlotinib inhibits human NSCLC cell growth predominantly by inducing p27(KIP1) expression and by suppressing cell-cycle events involved in the G1/S transition...

..Our data indicate that activation of BAX and BAK plays a critical role in the initiation of erlotinib-induced apoptotic cascades...

..These findings are significant and indicate that this combination may have broad therapeutic applications in a diverse range of lung tumors with different intrinsic chemosensitivities...

..These results have provided a rational basis for an ongoing clinical trial to explore this combination in patients with advanced malignant solid tumours...

..This study was undertaken to select the optimal combination schedule of erlotinib and pemetrexed for the treatment of relapsed non-small cell lung cancer (NSCLC) using a panel of human NSCLC lines...

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..A randomized, double-blinded, placebo-controlled study has been initiated to evaluate the clinical efficacy of menadione topical cream, in the treatment or prevention of EGFR inhibitor-induced skin toxicity...

..Grade 3 toxicities included fatigue (N=1, 8%), deep vein thrombosis (N=1, 8%) and thrombocytopenia (N=1, 8%). Although well tolerated, bortezomib monotherapy is not active in this cohort of chemotherapy-naïve, metastatic NSCLC...

..Further study of EGFR-modulated apoptotic pathways may facilitate the rational development of improved combination regimens...

..These data (a) provide evidence that both pathways converge on factors that regulate translation initiation and (b) support therapeutic strategies in lung cancer that simultaneously suppress the RAS and AKT signaling network...

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..This drug has demonstrated promising antitumor activity in Phase II trials in several solid tumors and definitive Phase III studies to demonstrate clinical benefit have completed accrual...

..All our data demonstrate that the caspase-mediated cleavage of beta-catenin, gamma-catenin, and APC protein might contribute to paclitaxel-induced apoptosis...

..Considered together, our results indicate that Ras proto-oncogenes can enhance or inhibit the malignant phenotype in vivo in different systems...

..The results indicate that loss of H-cadherin is frequent in human NSCLC and suggest that it facilitates the implantation and local growth of human NSCLC tumors...

..To develop an optimal nonviral aerosol formulation for locoregional treatment of early lung cancer...

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..This rationale becomes even more striking when one observes overexpression of Bcl2 in 70% of breast cancer, 30-60% of prostate cancer, 80% of B-cell lymphomas, 90% of colorectal adenocarcinomas, and many other forms of cancer...

..Most management strategies for these toxicities have been based on anecdotal experience; clinical trials are needed to provide uniform characterization to allow for evidence-based treatment strategies...

..Besides being a novel lead for the design of new anticancer tubulin ligands, the activity of 3-IAABE in the cell cycle may also help us to understand the molecular pharmacology of microtubule-active drugs...

..HER1/EGFR tyrosine kinase inhibitors may be more effective as second- or third-line treatment for certain patients with tumors that were previously treated with multiple chemotherapy regimens...

..This article will review several of these agents as well as their role in the treatment of non-small cell lung cancer...

..Thus ROS generation plays a critical role in the initiation of the bortezomib-induced apoptotic cascade by mediation of the disruption of Delta psi m and the release of cytochrome c from mitochondria...

..Taken together, our results indicate that wild-type N-ras has "tumor suppressor" activity, even in the absence of its oncogenic allele...

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..The resulting disturbance of cell cycle progression leads either to growth inhibition or to the initiation of apoptotic pathways...

..To investigate the safety and pharmacokinetics of aerosolized Sustained Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with lung carcinoma...

..DB67 and liposomal DB67 are more effective than irinotecan in the treatment of liver metastases after resection of the primary tumor...

..CONCLUSIONS: Our data suggest a role for Skp2 overexpression in prostate cancer pathogenesis that might not be exclusively related to p27 degradation. More studies are needed to determine the mechanistic role of Skp2 in prostate cancer...

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..Thus, endogenous thrombin contributes to tumor implantation, seeding, and spontaneous metastasis. A potent antithrombin agent should be of clinical benefit to patients with cancer...

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..To confirm the predictive value of the algorithm in a group of patients with chemoresistant NSCLC selected for their high probability of achieving a response or stable disease with single agent erlotinib therapy. ..

..To confirm the predictive value of the algorithm in a group of patients with chemoresistant NSCLC selected for their high probability of achieving a response or stable disease with single agent erlotinib therapy. ..

..abstract_text> ..

..Four such candidates have already been identified. It is anticipated that a total of ten young clinical investigators will be mentored during a five-year period. ..

..The results of this study will provide initial but very valuable information on the potential use of this new strategy in the treatment of bronchial premalignancy, carcinoma in situ, and endobronchial lung tumors. ..

..Ultimately, we will seek formulation(s) that display optimized drug retention and in vivo and in vitro performance. PROPOSED COMMERCIAL APPLICATION: Not Available ..