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Article
Targeting a lineage-specific PI3Kɣ–Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule
Dose-limiting toxicity poses a major limitation to the clinical utility of targeted cancer therapies, often arising from target engagement in nonmalignant tissues. This obstacle can be minimized by targeting c...
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Article
Open AccessPI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer
The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to...
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Article
Open AccessExecutioner caspases restrict mitochondrial RNA-driven Type I IFN induction during chemotherapy-induced apoptosis
During apoptosis, mitochondrial outer membrane permeabilization (MOMP) enables certain mitochondrial matrix macromolecules to escape into the cytosol. However, the fate of mitochondrial RNA (mtRNA) during apop...
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Article
P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia
Selinexor is a first-in-class inhibitor of the nuclear exportin XPO1 that was recently approved by the US Food and Drug Administration for the treatment of multiple myeloma and diffuse large B-cell lymphoma. I...
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Article
Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer
Local adaptation directs populations towards environment-specific fitness maxima through acquisition of positively selected traits. However, rapid environmental changes can identify hidden fitness trade-offs t...
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Article
Eccentric Enlargement of the Aortic Sinuses in Pediatric and Adult Patients with Bicuspid Aortic Valves: A Cardiac MRI Study
Aortic root size and cusp fusion pattern have been related to disease outcomes in bicuspid aortic valve (BAV). This study seeks to characterize symmetry of the aortic sinuses in adult and pediatric BAV patient...
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Article
Open AccessSynthetic lethality between HER2 and transaldolase in intrinsically resistant HER2-positive breast cancers
Intrinsic resistance to anti-HER2 therapy in breast cancer remains an obstacle in the clinic, limiting its efficacy. However, the biological basis for intrinsic resistance is poorly understood. Here we perform...
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Article
Open AccessSystematic map** of BCL-2 gene dependencies in cancer reveals molecular determinants of BH3 mimetic sensitivity
While inhibitors of BCL-2 family proteins (BH3 mimetics) have shown promise as anti-cancer agents, the various dependencies or co-dependencies of diverse cancers on BCL-2 genes remain poorly understood. Here w...
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Article
The Quantitative Structural and Compositional Analyses of Degenerating Intervertebral Discs Using Magnetic Resonance Imaging and Contrast-Enhanced Micro-Computed Tomography
The intervertebral disc (IVD) is susceptible to degenerative changes that are associated with low back pain. Murine models are often used to investigate the mechanistic changes in the development, aging, and ...
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Article
Open AccessPostnatal Development of the Murine Notochord Remnants Quantified by High-resolution Contrast-enhanced MicroCT
The notochord gives rise to spinal segments during development, and it becomes embedded within the nucleus pulposus of the intervertebral disc (IVD) during maturation. The disruption of the notochord band has ...
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Article
Open AccessTargeting MCL-1/BCL-XL Forestalls the Acquisition of Resistance to ABT-199 in Acute Myeloid Leukemia
ABT-199, a potent and selective small-molecule antagonist of BCL-2, is being clinically vetted as pharmacotherapy for the treatment of acute myeloid leukemia (AML). However, given that prolonged monotherapy te...
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Article
Open AccessVertical suppression of the EGFR pathway prevents onset of resistance in colorectal cancers
Molecular targeted drugs are clinically effective anti-cancer therapies. However, tumours treated with single agents usually develop resistance. Here we use colorectal cancer (CRC) as a model to study how the ...
