HDAC inhibition synergizes with ALK inhibitors to overcome resistance in a novel ALK mutated lung adenocarcinoma model

Objectives: Somatic chromosomal rearrangements resulting in ALK fusion oncogenes are observed in 3–7 % of lung adenocarcinomas. ALK tyrosine kinase inhibitors (ALKi) induce initially response, however, various resistance mechanisms limit their efficacy. Novel therapeutic approaches are of utmost importance to tailor these targeted therapies... Conclusion: Using a patient-derived ALKi resistant lung cancer model we demonstrated the synergism of HDAC and ALK inhibition. Furthermore, our findings provide strong evidence for intratumoral heterogeneity under targeted therapy and highlight the importance of site-specific mutational analysis. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.04.002

Authors: Paul Stockhammer, Cassandra Su Lyn Ho, Luca Hegedus, Gabor Lotz, Eszter Molnár, Agnes Bankfalvi, Thomas Herold, Stavros Kalbourtzis, Till Ploenes, Wilfried E. E. Eberhardt, Martin Schuler, Clemens Aigner, Alexander Schramm, Balazs Hegedus

Pre-ClinicalKirk SmithJune 1, 2020Anaplastic lymphoma kinase, Targeted therapy, Lung adenocarcinoma, Treatment resistance, Tumor heterogeneity

Concise Review: Resistance to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer: The Role of Cancer Stem Cells

Among the potential mechanisms involved in resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer, the manifestation of stem-like properties in cancer cells seems to have a crucial role. Alterations involved in the development of TKI resistance may be acquired in a very early phase of tumorigenesis, supporting the hypothesis that these aberrations may be present in cancer stem cells (CSCs). In this regard, the characterization of tumor subclones in the initial phase and the identification of the CSCs may be helpful in planning a specific treatment to target selected biomarkers, suppress tumor growth, and prevent drug resistance. The aim of this review is to elucidate the role of CSCs in the development of resistance to TKIs and its implication for the management of patients. READ ARTICLE

Stem Cells DOI:10.1002/stem.2787

Authors: Marzia Del Re, Elena Arrigoni, Giuliana Restante, Antonio Passaro, Eleonora Rofi, Stefania Crucitta, Filippo De Marinis, Antonello Di Paolo, Romano Danesi

Review PaperKirk SmithFebruary 5, 2018Cancer stem cells, Treatment resistance, Tyrosine kinase inhibitors, Biomarkers, Tumor heterogeneity