ALK-tyrosine kinase inhibitor intrinsic resistance due to -amplification in metastatic -rearranged non-small cell lung cancer effectively treated by alectinib-crizotinib combination-case report.

Background: Most patients with advanced anaplastic lymphoma kinase ()-rearranged (+) non-small cell lung cancer (NSCLC) experience prolonged response to second-generation (2G) ALK-tyrosine kinase inhibitors (TKIs). Herein, we present a case of metastatic + NSCLC rapidly progressing on first-line treatment due to amplification of the mesenchymal-epithelial transition factor () gene, which is a still elusive and underrecognized mechanism of primary resistance to ALK-TKIs.

Case Description: A 43-year-old, female diagnosed with T4N3M1c NSCLC harboring the echinoderm microtubule-associated protein-like 4 () fusion variant 1 ( v.

Real-World Data on Combined EGFR-TKI and Crizotinib Treatment for Acquired and De Novo Amplification in Patients with Metastatic -Mutated NSCLC.

Amplification of the () gene is a mechanism of acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine-kinase-inhibitors (TKIs) in over 20% of patients with advanced -mutated (m+) non-small lung cancer (NSCLC). However, it may also occur de novo in 2-8% of m+ NSCLC cases as a potential mechanism of intrinsic resistance. These patients represent a group with unmet needs, since there is no standard therapy currently approved.

Functional Proteomic Profiling of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that comprises various disease entities, all of which share a set of common features: a lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, respectively. Because of their receptor status, conventional chemotherapy remains the main therapeutic option for TNBC patients. We employed a reverse phase protein array approach (RPPA), complemented by immunohistochemistry, to quantitatively profile the activation state of 84 actionable key signaling intermediates and phosphoproteins in a set of 44 TNBC samples.

Intrinsic resistance to EGFR-Tyrosine Kinase Inhibitors in -Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance.

Activating mutations in the gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced -mutated (M+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20-30% of patients do not respond or respond for a very short time (<3 months) because of intrinsic resistance.