Anaplastic lymphoma kinase (ALK) is a tyrosine kinase associated with Anaplastic Large Cell lymphoma (ALCL) through oncogenic translocations mainly NPM-ALK. Chemotherapy is effective in ALK (+) ALCL patients and induces remission rates of approximately 80%.

Upfront polytherapy targeting ALK and MEK in ALK+ lung adenocarcinoma. Shown is a schematic of the critical role of RAS-RAF-MEK-ERK (RAS-MAPK) signaling in ALK+ (EML4-ALK positive) tumor cells, and the rational co-targeting strategy to inhibit both ALK and MEK to enhance response. MAPK, mitogen activated protein kinase; ALK, anaplastic lymphoma ...

Jan 11, 2018 · We document that ALK activation induces ETV5 protein upregulation through stabilization in a MEK/ERK-dependent manner. We show that RNAi-mediated inhibition of ETV5 decreases RET expression. Reporter assays indicate that ETV5 is …

Nov 2, 2024 · Here, we use optogenetics and live-cell imaging to find that EML4-ALK assemblies suppress transmembrane receptor tyrosine kinase (RTK) signaling by sequestering RTK adapter proteins including...

Mar 7, 2025 · In this Review, we discuss recent advances in ALK oncogenic signalling, together with existing and promising new modalities to treat ALK-driven tumours, including currently approved ALK-directed...

Oct 29, 2015 · ALK (anaplastic lymphoma kinase) inhibitors are approved in for ALK gene rearrangement positive (ALK+) lung cancer, but resistance remains a challenge. We discovered that RAS-RAF-MEK-ERK signaling controls the ALK inhibitor response in ALK+ lung cancer and is critical for ALK inhibitor resistance.

Note: EML4-ALK is localized in the cytoplasm and primarily promotes cell proliferation, invasion, metastasis, and inhibits apoptosis through three signaling pathways: the MAPK/MEK/ERK, PI3K/AKT, and JAK/STAT3 pathways. In the figure, purple represents genes, pink denotes kinases, and light yellow indicates transcription factors.

Apr 10, 2025 · Raf/MEK/ERK signalling is considered to be a major RAS effector pathway, but single-agent activity for MAPK inhibitors in KRASMT CRC has shown to be ineffective [6, 7]. ... Tan W, et al. Pharmacokinetics (PK) of PF-02341066, a dual ALK/MET inhibitor after multiple oral doses to advanced cancer patients. J Clin Oncol. 2010;28:2596.

Anaplastic lymphoma kinase (ALK) alterations in non-small cell lung cancer (NSCLC) can be effectively treated with a variety of ALK-targeted drugs. After the approval of the first-generation ALK inhibitor crizotinib which achieved better results in ...

Jan 11, 2018 · We document that ALK activation induces ETV5 protein upregulation through stabilization in a MEK/ERK-dependent manner. We show that RNAi-mediated inhibition of ETV5 decreases RET expression....