... targeted and non-targeted therapies. Here we report the first safety and interim efficacy of sotorasib and afatinib, a pan-ErbB tyrosine kinase inhibitor, that had displayed synergistic antitumor activity in vitro. Methods: Patients with advanced KRAS p.G12C mutated NSCLC who had...

... Format: Jeff Hsu, Colin Chong, Jeffrey Serrill, Sharon Wu, Kevin Leong, Ted Yun, Lynne Bannen, Peter Lamb, Wei Xu, Peiwen Yu. The tyrosine kinase inhibitor XL092 promotes an immune-permissive tumor microenvironment and enhances the anti-tumor activity of immune checkpoint inhibitors in preclinical...

... are associated with treatment-free remission following discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia . Mol Cancer Ther 2021 ; 20 : 142 – 9 . ...

... are clinically effective in MET-amplified and MET exon 14 deletion mutant (METex14) non–small cell lung cancers (NSCLCs), but their efficacy is limited by the development of drug resistance. Structurally distinct MET tyrosine kinase inhibitors (TKIs) (type I/II) have been developed...

... clinical benefit and response durability. Entrectinib, a NTRK/ROS1/ALK targeted tyrosine kinase inhibitor (TKI), was approved for the treatment of ROS1 fusion-positive non–small cell lung cancer (NSCLC) in 2019. In addition, lorlatinib and repotrectinib are actively being explored in the setting...

... no. HHSN261200800001E. Citation Format: Thomas S. Dexheimer, Julie Laudeman, Thomas Silvers, Rene Delosh, Russell Reinhart, Chad Ogle, Eric Jones, Nathan P. Coussens, Beverly A. Teicher, Naoko Takebe, Alice Chen, James H. Doroshow. Combinations of receptor tyrosine kinase inhibitors targeting the tumor and stromal...

... abolished their remaining ERK activity. SHP099 administered in combination with molecular-targeted therapy resulted in marked growth inhibition of cancer cells both in vitro and in vivo. Thus, treatment combining an SHP2 inhibitor and a tyrosine kinase inhibitor may be a promising...

...Nicolas Floc'h; Sangbin Lim; Sue Bickerton; Afshan Ahmed; Jonathan Orme; Jelena Urosevic; Matthew J. Martin; Darren A.E. Cross; Byoung Chul Cho; Paul D. Smith Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI...

... of development, but resistance remains an important clinical problem. FF-10101 is the first irreversible, covalent inhibitor of FLT3 which has previously shown activity against FLT3 tyrosine kinase inhibitor resistance–causing FLT3 F691L and D835 mutations. We report that FF-10101 is also active against...

... between TFR and polymorphisms of KIRs and HLAs in patients who discontinued tyrosine kinase inhibitors (TKI). Seventy-six patients were enrolled, and their KIR and HLA polymorphisms and natural killer (NK) cell activation status were investigated as previously described...

...-targeted small-molecule tyrosine kinase inhibitor. In both biochemical and cell signaling experiments, tucatinib inhibits HER2 kinase activity with single-digit nanomolar potency and provides exceptional selectivity for HER2 compared with the related receptor tyrosine kinase EGFR, with a >1,000-fold...

... support further study of RRSP-DTB as an unprecedented RAS biodegrader for RAS-addicted tumors. Clinical outcomes in FLT3-mutant acute myeloid leukemia (AML) remain exceedingly poor due to FLT3 tyrosine kinase inhibitor (TKI) resistance. FF-10101 is the first covalent FLT3 inhibitor...

... patients with advanced NSCLC [1, 2]. EGFR tyrosine kinase inhibitors 24 (TKIs) have revolutionized the treatment paradigm for NSCLC patients. The first and 25 second generation EGFR TKIs, such as gefitinib, erlotinib and afatinib, provide 26 dramatic clinical benefits for NSCLC patients with sensitizing...

... mutations dominate in AML driven by the mutant forms of this enzyme, other receptor tyrosine kinases, their ligands and a host of intracellular signaling pathways, including RAS/MAPK and AURK, mediate resistance to inhibitors of FLT3 or other important targets for AML, such as BCL2 (5-10). Collectively...

... target for overcoming EGFR inhibitor resistance. Clin Cancer Res, 2013. 19(1): p. 27990. Quinn, J.M., M.M. Greenwade, M.L. Palisoul, G. Opara, K. Massad, L. Guo, et al., Therapeutic Inhibition of the Receptor Tyrosine Kinase AXL Improves Sensitivity to Platinum and Taxane in Ovarian Cancer. Mol Cancer...

... , . CDK4/6 inhibition as maintenance and combination therapy for high grade serous ovarian cancer . Oncotarget 2018 ; 9 : 15658 – 72 . 21. Kelland LR . Flavopiridol, the first cyclin-dependent kinase inhibitor to enter the clinic: current status . Expert Opin Investig Drugs 2000 ; 9...

... carcinoma. Cancer Res, 2014. 74(24): p. 7191-7. 51. Kesarwani, M., Z. Kincaid, A. Gomaa, E. Huber, S. Rohrabaugh, Z. Siddiqui, et al., Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia. Nat Med, 2017. 23(4): p. 472-482. 52. Jandial, D.D...

... metastases: a retrospective, exploratory analysis in EMILIA . Ann Oncol 2015 ; 26 : 113 – 9 . 24. Kulukian A , Lee P , Taylor J , Rosler R , de Vries P , Watson D , . Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single...

... to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells . Head Neck 2014 ; 36 : 1547 – 54 . 43. Rampias T , Giagini A , Siolos S , Matsuzaki H , Sasaki C , Scorilas A , . RAS/PI3K crosstalk...

... approaches involving more than one HER receptor. Because the tyrosine kinase activity of HER3 is impaired, conventional targeting approaches involving ATP-competitive small-molecule inhibitors are not effective. Functional blockade is rather achieved by antibodies directed toward the extracellular domain...