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Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F.
In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain, and sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation.
Small-molecule p21-activated kinase inhibitor PF-3758309 is a potent inhibitor of oncogenic signaling and tumor growth
PAK4-related pathways are defined, additional support for PAK4 as a therapeutic target with a unique combination of functions (apoptotic, cytoskeletal, cell-cycle), and a potent, orally available small-molecule PAK inhibitor with significant promise for the treatment of human cancers is identified.
Spectrum and Degree of CDK Drug Interactions Predicts Clinical Performance
Therapeutically targeting aberrant intracellular kinase signaling is attractive from a biological perspective but drug development is often hindered by toxicities and inadequate efficacy, so understanding the molecular components of potency and selectivity facilitates rational design of future generations of kinase-directed drugs.
Targeting activin receptor-like kinase 1 inhibits angiogenesis and tumorigenesis through a mechanism of action complementary to anti-VEGF therapies.
Given the observation of its expression in the vasculature of many human tumor types and in circulating ECs from patients with advanced cancers, ALK1 blockade may represent an effective therapeutic opportunity complementary to the current antiangiogenic modalities in the clinic.
Covalent EGFR inhibitor analysis reveals importance of reversible interactions to potency and mechanisms of drug resistance
Previously uncharacterized investigational covalent drugs reported here are shown to be extremely effective epidermal growth factor receptor (EGFR) inhibitors, despite their low specific reactivity, which is compensated for by high binding affinities.
Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity
The mechanism of action and robust anti-tumor efficacy of PF-05082566 support its clinical development for the treatment of a broad spectrum of human malignancies.
Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer
The data indicated that treatment of tumor bearing mice with AOM1 as a single agent or in combination with Carboplatin significantly inhibited growth of large metastatic tumors in the lung further supporting a role for OPN in tumor metastasis and progression.