Guide to Targeted Therapies: Treatment Resistance in Lung by Federico Cappuzzo

By Federico Cappuzzo

This textual content is a concise and updated evaluation, which discusses the heritage, improvement and mechanisms of resistance, checking out equipment and expertise, present and rising treatments and assets that clinicians promises to their sufferers. Busy healthcare pros who desire a speedy assessment of therapy resistance in lung melanoma in addition to a precis of present treatments will reap the benefits of this succinct guide.

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2012;13:1011-1019. 68 Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALKpositive lung cancer. N Engl J Med, 2013; 368: 2385–94. 69 Mok T, Kim D-W, Wu Y-L, et al. First-line crizotinib versus pemetrexed–cisplatin or pemetrexed– carboplatin in patients (pts) with advanced ALK-positive non-squamous non-small cell lung cancer (NSCLC): results of a phase III study (PROFILE 1014). J Clin Oncol. 2014; 32:5s (suppl; abstr 8002). 70 Kwak EL, Camidge DR, Clark J, et al. Clinical activity observed in a phase I dose escalation trial of an oral anti c-met and ALK inhibitor, PF-02341066.

Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol. 2010; 28: 357-360. 2 Chaft JE, Oxnard GR, Sima CS, et al. Disease flare after tyrosine kinase inhibitor discontinuation in patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib: implications for clinical trial design. Clin Cancer Res. 2011;17:6298-6303. 48 • GUID E TO TA R G E TE D THE R A P IE S: T RE AT M E N T RE S IS TA N CE IN LU N G C AN C E R 3 Guo R, Chen X, Wang T, et al.

A randomized phase II study of erlotinib alone or in combination with linsitinib (OSI-906), an orally bioavailable small molecule inhibitor of IGF1R, in patients with advanced EGFR mut+ NSCLC was prematurely closed for futility (NCT01221077). The potential efficacy of rociletinib in the T790M-negative population could be, at least in part, related to IGF1R inhibition. Hyperglycemia, a frequent adverse event associated with rociletinib exposure, is related to a rociletinib metabolite that is able to inhibit IGF1R.

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