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4d
MICALL2 promotes angiogenesis of colorectal cancer by regulating the EGFR/PI3K/AKT/KLF5/VEGFA axis. (PubMed, Biochem Pharmacol)
Pharmacological inhibition of PI3K via LY294002 reversed MICALL2-induced angiogenesis. Therefore, MICALL2 facilitates CRC angiogenesis through the EGFR/PI3K/AKT/KLF5/VEGFA axis and may serve as a promising target for anti-angiogenic therapy.
Journal
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EGFR (Epidermal growth factor receptor)
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LY294002
4d
Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis. (PubMed, Sci Adv)
Pharmacological inhibition of FAK with single agent VS-4718 did not significantly reduce macroscopic tumor volume; however, its use in combination with the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib resulted in both a significant reduction in tumor volume and the preservation of dorsal root ganglion architecture. Our findings establish a critical role for FAK in schwannoma development and provide rationale for evaluation of combination FAK plus MEK inhibition in future clinical trials for NF2-associated SWN.
Preclinical • Journal
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HGF (Hepatocyte growth factor) • NF2 (Neurofibromin 2) • NLRC5 (NLR Family CARD Domain Containing 5) • PTK2 (Protein Tyrosine Kinase 2)
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Koselugo (selumetinib) • VS-4718
6d
Overexpression of IL7R Attenuates Cerebral Ischemia-Reperfusion Injury by Inhibiting Apoptosis. (PubMed, J Integr Neurosci)
Overexpression of IL7R was shown to alleviate CIRI by suppressing apoptosis. These findings indicate IL7R as a novel target for IS treatment.
Journal • IO biomarker
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IL7R (Interleukin 7 Receptor) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • IL7 (Interleukin 7)
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LY294002
7d
A Study of Avutometinib (VS-6766) and Defactinib in People With Mesonephric Gynecologic Cancer (clinicaltrials.gov)
P2, N=40, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027
Trial completion date • Trial primary completion date
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Avmapki (avutometinib) • Fakzynja (defactinib)
13d
Mechanisms of electroacupuncture at Foot Shaoyang meridian acupoints on inflammatory response in postmenopausal osteoporosis rats based on the PI3K/AKT signaling pathway (PubMed, Zhen Ci Yan Jiu)
EA at Foot Shaoyang meridian acupoints can alleviate inflammatory responses and bone loss in postmenopausal osteoporosis rats, and its mechanism may be related to the activation of the PI3K/AKT pathway.
Preclinical • Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL1B (Interleukin 1, beta) • RUNX2 (RUNX Family Transcription Factor 2)
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LY294002
14d
Downregulation of OPCML is associated with activation of AKT signaling and aggressive phenotypes in glioblastoma cells. (PubMed, Front Oncol)
Functional validation used a single OPCML small interfering RNA (siRNA) with a non-targeting siRNA control (siNC) in U87 and U251 cells with Transwell invasion, wound healing, colony formation, CCK-8 proliferation, and Western blotting for p-AKT and p-mTOR, with LY294002 rescue...Loss of OPCML aligns with proliferative programs and a GBM-specific immune pattern. These data nominate OPCML as a prognostic marker and a surface-level modulator that could be leveraged alongside RTK/PI3K axis inhibitors in GBM.
Journal
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OPCML (Opioid Binding Protein/Cell Adhesion Molecule Like)
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IDH wild-type
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LY294002
14d
Long lasting response to the combination of Avutometinib and Defactinib after progression on Binimetinib in a patient with recurrent low grade serous ovarian carcinoma - A case report. (PubMed, Gynecol Oncol Rep)
The oral drug combination was well tolerated with no dose-limiting toxicity or need for dose reduction over the 4 year period. The Avutometinib and Defactinib combination may represent a new standard treatment option for platinum-resistant and AI-resistant/recurrent LGSOC who have failed other MEKi.
Journal
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KRAS (KRAS proto-oncogene GTPase) • MUC16 (Mucin 16, Cell Surface Associated)
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KRAS mutation
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Mektovi (binimetinib) • Avmapki (avutometinib) • Fakzynja (defactinib)
14d
Targeting focal adhesion kinase (FAK) in non-small cell lung cancer (NSCLC): Molecular mechanisms and combination therapeutic strategies. (PubMed, Biochem Pharmacol)
Several FAK targeted inhibitors have advanced into clinical evaluation; for example, CEP-37440 is undergoing phase I trials, whereas GSK-2256098 has reached phase II trials. This review summarizes the structure and functional characteristics of FAK, its role in the pathogenesis of NSCLC, the research progress on FAK inhibitors, and the current status and prospects of combining FAK inhibitors with other therapies for NSCLC. The aim is to provide new insights for future clinical trial design and combination therapy strategies for NSCLC.
Review • Journal
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
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GSK2256098 • CEP-37440
18d
a Study to Evaluate the Safety and Efficacy of D-1553 Combined With IN10018 in KRAS G12C Mutant Solid Tumors (clinicaltrials.gov)
P1/2, N=140, Recruiting, InxMed (Shanghai) Co., Ltd. | Trial completion date: Dec 2026 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2027
Trial completion date • Trial primary completion date
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KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12
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Anfangning (garsorasib) • ifebemtinib (IN10018)
18d
Enrollment open
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12C • KRAS G12
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cisplatin • carboplatin • Tevimbra (tislelizumab-jsgr) • pemetrexed • Anfangning (garsorasib) • ifebemtinib (IN10018)
19d
IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma (clinicaltrials.gov)
P1, N=51, Completed, InxMed (Shanghai) Co., Ltd. | Active, not recruiting --> Completed | N=120 --> 51
Trial completion • Enrollment change
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NRAS (Neuroblastoma RAS viral oncogene homolog)
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NRAS mutation • NRAS Q61 • NRAS G12 • NRAS G13
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Tecentriq (atezolizumab) • Cotellic (cobimetinib) • ifebemtinib (IN10018)
22d
RAMP 203: Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients (clinicaltrials.gov)
P1/2, N=153, Active, not recruiting, Verastem, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2025 --> Jun 2026
Enrollment closed • Trial primary completion date
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KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12
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Lumakras (sotorasib) • Avmapki (avutometinib) • Fakzynja (defactinib)