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Therefore, the activity of the anticancer marine drug fascaplysin was tested against primary NSCLC cell lines established from pleural effusions. Cytotoxicity of the drug or combinations were determined using MTT assays and changes in intracellular phosphorylation by Western blot arrays. Fascaplysin revealed high cytotoxicity against NSCLC cells and exhibit an activity pattern different of the standard drug cisplatin. Furthermore, fascaplysin synergizes with the EGFR tyrosine kinase inhibitor (TKI) afatinib to yield a twofold increased antitumor effect. Interaction with the Chk1\/2 inhibitor AZD7762 confirm the differential effects of fascplysin and cisplatin. Protein phosphorylation assays showed hypophosphorylation of Akt1\/2\/3 and ERK1\/2 as well as hyperphosphorylation of stress response mediators of H1299 NSCLC cells. In conclusion, fascaplysin shows high cytotoxicity against pleural primary NSCLC lines that could be further boosted when combined with the EGFR TKI afatinib.<\/jats:p>","DOI":"10.1007\/s10637-021-01181-8","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T05:11:31Z","timestamp":1633065091000},"page":"215-223","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synergistic cytotoxicity of the CDK4 inhibitor Fascaplysin in combination with EGFR inhibitor Afatinib against Non-small Cell Lung Cancer"],"prefix":"10.1007","volume":"40","author":[{"given":"Adelina","family":"Plangger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Rath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Hochmair","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Funovics","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Neumayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Zeillinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4038-5182","authenticated-orcid":false,"given":"Gerhard","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"issue":"Suppl2","key":"1181_CR1","doi-asserted-by":"publisher","first-page":"s41","DOI":"10.7861\/clinmedicine.18-2-s41","volume":"18","author":"GS Jones","year":"2018","unstructured":"Jones GS, Baldwin DR (2018) Recent advances in the management of lung cancer. 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The authors declare no conflict of interest related to the present work.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}