Anticancer drugs: How to select small molecule combinations?

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(6), P. 503 - 519

Published: May 22, 2024

Language: Английский

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RAS-ON inhibition overcomes clinical resistance to KRAS G12C-OFF covalent blockade

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 30, 2024

Selective KRAS

Language: Английский

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HRS-4642: The next piece of the puzzle to keep KRAS in check

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(7), P. 1157 - 1159

Published: July 1, 2024

Language: Английский

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Natural products targeting RAS by multiple mechanisms and its therapeutic potential in cancer: An update since 2020

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107577 - 107577

Published: Jan. 5, 2025

RAS proteins, as pivotal signal transduction molecules, are frequently mutated and hyperactivated in various human cancers, closely associated with tumor cell proliferation, survival, metastasis. Despite extensive research on targeted therapies, developing effective inhibitors remains a significant challenge. Natural products, endowed unique chemical structures diverse biological activities through long-term natural selection, have emerged vital resource for discovering novel RAS-targeted therapeutic drugs. This review focuses the latest advancements targeting products categorizes these based their mechanisms of action. Additionally, we discuss challenges faced by during clinical translation, including issues related to pharmacokinetics. Strategies such combination therapy, structural optimization, drug delivery systems anticipated enhance efficacy overcome challenges. multiple mechanisms.

Language: Английский

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Cycling Molecular Assemblies for Selective Cancer Cell Golgi Disruption

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

The Golgi apparatus is a critical organelle responsible for intracellular trafficking and signaling, orchestrating essential processes such as protein lipid sorting

Language: Английский

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Visible Light-Triggered Single-Component Photocage Nanoparticles for Combinatorial Photodynamic Therapy and Chemotherapy

ACS Applied Nano Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Language: Английский

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STAT3 Inhibition Prevents Adaptive Resistance and Augments NK Cell Cytotoxicity to KRAS^G12C Inhibitors in Nonsmall Cell Lung Cancer

Cancer Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

KRASG12C inhibitors exhibit conspicuous clinical response in KRASG12C-mutant lung cancer, yet adaptive resistance, the rapid onset of intrinsic dampens their therapeutic success. Rational combination strategies could tackle this challenging problem. A high-throughput screening a pharmacological library with 423 compounds revealed that napabucasin, signal transducer and activator transcription 3 (STAT3) inhibitor, synergistically potentiated growth inhibition effect inhibitor sotorasib sensitive resistant NSCLC cell lines. Functional assays further coordinated targeting KRAS STAT3 improved inhibitory on tumor augmented infiltration activation natural killer (NK) cells within microenvironment. Mechanistically, induced compensatory STAT3, contingent concomitant suppression downstream ERK signaling, abrogated by napabucasin. Moreover, we unveiled verified binding site phosphorylated at HLA-B promoter, an ligand for NK cells. Our study dissected unknown mechanism resistance to inhibitors, sustaining regrowth under up-regulating dampen cytotoxicity infiltrated

Language: Английский

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Reducing pERKs to Break “RAS”istance to Sotorasib

Journal of Thoracic Oncology, Journal Year: 2025, Volume and Issue: 20(3), P. 259 - 261

Published: March 1, 2025

Language: Английский

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Targeting RAS and associated proteins

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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The Persistent Power of the Taxane/Platin Chemotherapy

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1208 - 1208

Published: April 2, 2025

The cancer chemotherapy regimen of a taxane and platinum combination was developed more than forty years ago, yet remains the cornerstone treatment for several major types today. Although many new agents targeting genes pathways have been evaluated, none sufficient to replace long-established taxane/platinum combination. This leads us ponder why, after four decades colossal efforts, multiple discoveries, tremendous advances in understanding gene mutations biology, development conceptually superior targeted therapies has not achieved overwhelming success replacing cytotoxic chemotherapy. concept therapy is based on idea that blocking altered pathway(s) crucial (and maintenance), disturbance cellular signaling, metabolism, functions will make cells unfit trigger programmed cell death cells, but without significant side effects limit We propose lack anticipated triumphs stems from desensitization during neoplastic transformation malignant progression cells. renders drugs largely ineffective at killing mostly insufficient clinical implements. Recent suggest that, contrast therapies, taxanes kill by physical rupturing nuclear membranes rather triggering apoptosis, making their effect independent intrinsic mechanism. recognition non-programmed mechanism chemotherapeutic agents, such as platinum, may inspire oncologists researchers focus efforts productively developing effective or significantly improve application current standard regimens.

Language: Английский

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