Targeting RAS–RAF–MEK–ERK signaling pathway in human cancer: Current status in clinical trials

Genes & Diseases, Год журнала: 2022, Номер 10(1), С. 76 - 88

Опубликована: Май 20, 2022

Molecular target inhibitors have been regularly approved by Food and Drug Administration (FDA) for tumor treatment, most of them intervene in cell proliferation metabolism. The RAS-RAF-MEK-ERK pathway is a conserved signaling that plays vital roles proliferation, survival, differentiation. aberrant activation the induces tumors. About 33% tumors harbor RAS mutations, while 8% are driven RAF mutations. Great efforts dedicated to targeting cancer treatment past decades. In this review, we summarized development with an emphasis on those used clinical treatment. Moreover, discussed potential combinations other pathways. essentially modified therapeutic strategy against various cancers deserve more attention current research

Язык: Английский

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Metastasis and MAPK Pathways

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(7), С. 3847 - 3847

Опубликована: Март 31, 2022

Cancer is a leading cause of death worldwide. In many cases, the treatment disease limited due to metastasis cells distant locations body through blood and lymphatic drainage. Most anticancer therapeutic options focus mainly on inhibition tumor cell growth or induction death, do not consider molecular basis metastasis. The aim this work provide comprehensive review focusing cancer mitogen-activated protein kinase (MAPK) pathway (ERK/JNK/P38 signaling) as crucial modulator process.

Язык: Английский

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Targeting MAPK-ERK/JNK pathway: A potential intervention mechanism of myocardial fibrosis in heart failure

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 173, С. 116413 - 116413

Опубликована: Март 9, 2024

Myocardial fibrosis is a significant pathological basis of heart failure. Overactivation the ERK1/2 and JNK1/2 signaling pathways MAPK family members synergistically promotes proliferation myocardial fibroblasts accelerates development fibrosis. In addition to some small molecule inhibitors Western drugs, many Chinese medicines can also inhibit activity JNK1/2, thus slowing down fibrosis, are generally safe effective. However, specific biological mechanisms in still need be fully understood, there no systematic review existing drugs methods them from improving This study aims summarize roles cross-linking systematically sort out small-molecule inhibitors, traditional medicines, non-pharmacological therapies that alleviate future, we hope conduct more in-depth research perspective precision-targeted therapy, using this as for developing new provide perspectives on prevention treatment

Язык: Английский

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Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies

Orthopaedic Surgery, Год журнала: 2024, Номер 16(3), С. 532 - 550

Опубликована: Янв. 31, 2024

Osteoarthritis (OA) is the most common chronic degenerative joint disease in middle‐aged and elderly people, characterized by pain dysfunction. Macrophages are key players OA pathology, their activation state has been studied extensively. Various studies have suggested that macrophages might respond to stimuli microenvironment changing phenotypes pro‐inflammatory or anti‐inflammatory phenotypes, which called macrophage polarization. accumulate become polarized (M1 M2) many tissues, such as synovium, adipose tissue, bone marrow, mesenchymal tissues joints, while resident well other stromal cells, including fibroblasts, chondrocytes, osteoblasts, form function an integrated unit. In this study, we focus exclusively on synovial macrophages, tissue osteoclasts, investigate roles development of OA. We review recent findings related polarization OA, pathogenesis, molecular pathways, therapeutics. summarize several signaling pathways reprogramming NF‐κB, MAPK, TGF‐β, JAK/STAT, PI3K/Akt/mTOR, NLRP3. Of note, despite increasing availability treatments for osteoarthritis, like intra‐articular injections, surgery, cellular therapy, demand more effective clinical therapies remained steady. Therefore, also describe current prospective therapeutic methods deem be a target, physical stimulus, chemical compounds, biological molecules, enhance cartilage repair alleviate progression

Язык: Английский

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Natural products modulating MAPK for CRC treatment: a promising strategy

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 5, 2025

Colorectal cancer (CRC) is a common malignant tumor of the digestive system, and pathogenic mechanism still unclear, mostly related to genetics, immunity, inflammation, abnormal activation tumor-related signaling pathways. MAPK belongs Ser/Thr kinase family, which plays an important role in complex cellular programs such as regulation cell proliferation, differentiation, apoptosis, angiogenesis, metastasis. Increasing evidence supports that highly correlated with risk CRC. Targeting may be therapeutic strategy, natural products show great potential regulating MAPK-related proteins. In this paper, we searched PubMed, Web Science CNKI databases keywords "colorectal cancer, products, pathway, ERK, P38, JNK" for relevant studies last 14 years from 2010 2024. This work retrieved 47 studies, aiming provide new strategies CRC patients lay foundation drug development.

Язык: Английский

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The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer

International Journal of Molecular Sciences, Год журнала: 2021, Номер 23(1), С. 370 - 370

Опубликована: Дек. 29, 2021

The mitogen-activated protein kinase (MAPK) family is an important bridge in the transduction of extracellular and intracellular signals different responses at cellular level. Within this MAPK family, p38 kinases can be found altered various diseases, including cancer, where these play a fundamental role, sometimes with antagonistic mechanisms action, depending on several factors. In fact, has immense number functionalities, many them yet to discovered terms regulation action types being directly involved response cancer therapies. To date, three main groups MAPKs have been identified mammals: signal-regulated (ERK), Jun N-terminal (JNK), isoforms (α, β, γ, δ). review, we highlight mechanism kinases, taking into account their extensive level through modifications modulations, wide variety microRNAs. We also analyze importance expressed tissues possible role as biomarkers molecular targets. addition, include latest preclinical clinical trials p38-related drugs that are ongoing hopeful expectations present/future developing precision medicine cancer.

Язык: Английский

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The multifaceted mechanisms of Paeoniflorin in the treatment of tumors: State-of-the-Art

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 149, С. 112800 - 112800

Опубликована: Март 9, 2022

Paeoniflorin is a water-soluble monoterpenoid glycoside that can be derived from multiple herbaceous plants, such as Radix Paeoniae Rubra, Alba, Paeonia suffruticosa and Cimicifugae Foetidae. Multiple studies have suggested possesses an excellent anti-tumor effect in variety of tumors, including liver cancer, gastric breast lung pancreatic colorectal cancer bladder cancer. It induce cell apoptosis, inhibit proliferation, invasion metastasis via different molecular mechanisms, which are mainly involved nuclear transcription factor kappα (NF-κB), B-cell lymphoma-2(Bcl-2) family, MicroRNA, neural precursor expressed developmentally down-regulated protein 4(NEDD4) signaling pathway, activating (STAT3), p21, p53/14-3-3 transforming growth factor-β1(TGF-β1)/Smads Mitogen-activated kinase (MAPK) pathway Notch-1. Current on mechanism action remain unclear. Therefore, this study reviews the research progress attempt to provide new thought theoretical basis for further development clinical application Paeoniflorin.

Язык: Английский

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Exosomal miR-155-5p drives widespread macrophage M1 polarization in hypervirulent Klebsiella pneumoniae-induced acute lung injury via the MSK1/p38-MAPK axis

Cellular & Molecular Biology Letters, Год журнала: 2023, Номер 28(1)

Опубликована: Ноя. 13, 2023

Hypervirulent Klebsiella pneumoniae (hvKp) infection-induced sepsis-associated acute lung injury (ALI) has emerged as a significant clinical challenge. Increasing evidence suggests that activated inflammatory macrophages contribute to tissue damage in sepsis. However, the underlying causes of widespread macrophage activation remain unclear.BALB/c mice were intravenously injected with inactivated hvKp (iHvKp) observe damage, inflammation, and M1 polarization. In vitro, RAW264.7 macrophage-derived exosomes (iHvKp-exo) isolated their role ALI formation was investigated. RT-PCR conducted identify changes exosomal miRNA. Bioinformatics analysis dual-luciferase reporter assays performed validate MSK1 direct target miR-155-5p. Further vivo vitro experiments explore specific mechanisms involved.iHvKp successfully induced upregulated expression vivo, injection iHvKp-exo found promote response polarization through p38-MAPK pathway. revealed exposure time-dependent increased levels miR-155-5p iHvKp-exo. Dual-luciferase confirmed functional mediating effects by targeting MSK1. Additionally, inhibition reduced resulting decreased inflammation or iHvKp.The aforementioned results indicate drives hvKp-induced MSK1/p38-MAPK Axis.

Язык: Английский

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Comparison of Quantitative Mass Spectrometric Methods for Drug Target Identification by Thermal Proteome Profiling

Journal of Proteome Research, Год журнала: 2023, Номер 22(8), С. 2629 - 2640

Опубликована: Июль 13, 2023

Thermal proteome profiling (TPP) provides a powerful approach to studying proteome-wide interactions of small therapeutic molecules and their target off-target proteins, complementing phenotypic-based drug screens. Detecting differences in thermal stability due engagement requires high quantitative accuracy consistent detection. Isobaric tandem mass tags (TMTs) are used multiplex samples increase quantification precision TPP analysis by data-dependent acquisition (DDA). However, advances data-independent (DIA) can provide higher sensitivity protein coverage with reduced costs sample preparation steps. Herein, we explored the performance different DIA-based label-free approaches compared TMT-DDA for shift quantitation. Acute myeloid leukemia cells were treated losmapimod, known inhibitor MAPK14 (p38α). Label-free DIA approaches, particularly library-free mode DIA-NN, comparable ability detect losmapimod one its downstream targets, MAPKAPK3. Using quantitation is cost-effective alternative labeled pipeline.

Язык: Английский

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Targeting PI3K/Akt in Cerebral Ischemia Reperfusion Injury Alleviation: From Signaling Networks to Targeted Therapy

Molecular Neurobiology, Год журнала: 2024, Номер 61(10), С. 7930 - 7949

Опубликована: Март 5, 2024

Язык: Английский

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