Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: May 31, 2021

Abstract Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since first tyrosine kinase inhibitor imatinib was approved enter market by US Food Drug Administration (FDA) 2001, an increasing number of small-molecule been developed for treatment malignancies. By December 2020, 89 antitumor FDA National Medical Products (NMPA) China. Despite great progress, anti-cancer still face many challenges, such as a low response rate drug resistance. To better promote development we conducted comprehensive review according target classification. We present all well important candidates clinical trials each target, discuss current provide insights perspectives research drugs.

Language: Английский

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Targeting TGFβ signal transduction for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Jan. 7, 2021

Abstract Transforming growth factor-β (TGFβ) family members are structurally and functionally related cytokines that have diverse effects on the regulation of cell fate during embryonic development in maintenance adult tissue homeostasis. Dysregulation TGFβ signaling can lead to a plethora developmental disorders diseases, including cancer, immune dysfunction, fibrosis. In this review, we focus TGFβ, well-characterized member has dichotomous role cancer progression, acting early stages as tumor suppressor late promoter. The functions not limited proliferation, differentiation, apoptosis, epithelial–mesenchymal transition, metastasis cells. Recent reports cells present microenvironment through stimulation extracellular matrix deposition, promotion angiogenesis, suppression anti-tumor reaction. pro-oncogenic roles attracted considerable attention because their intervention provides therapeutic approach for patients. However, critical function maintaining homeostasis makes targeting challenge. Here, review pleiotropic initiation summarize recent clinical advancements regarding interventions treatment, discuss remaining challenges opportunities pathway. We provide perspective synergistic therapies combine anti-TGFβ therapy with cytotoxic chemotherapy, targeted therapy, radiotherapy, or immunotherapy.

Language: Английский

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Autophagy as a therapeutic target in pancreatic cancer

British Journal of Cancer, Journal Year: 2020, Volume and Issue: 124(2), P. 333 - 344

Published: Sept. 15, 2020

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterised by early metastasis and resistance to anti-cancer therapy, leading an overall poor prognosis. Despite continued research efforts, no targeted therapy has yet shown meaningful efficacy in PDAC; mutations the oncogene KRAS tumour suppressor TP53, which are most common genomic alterations PDAC, have so far clinical actionability. Autophagy, a conserved process allowing cells recycle altered or unused organelles cellular components, been be upregulated PDAC implicated both cytotoxic chemotherapy therapy. Autophagy thus regarded as potential therapeutic target other cancers. Although molecular mechanisms of autophagy activation only beginning emerge, several groups reported interesting results when combining inhibitors extracellular-signal-regulated kinase/mitogen-activated protein kinase pathway models KRAS-driven In this article, we review existing preclinical data regarding role well relevant trials with agents that modulate cancer.

Language: Английский

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Mechanisms of Resistance and Current Treatment Options for Glioblastoma Multiforme (GBM)

Cancers, Journal Year: 2023, Volume and Issue: 15(7), P. 2116 - 2116

Published: April 1, 2023

Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer that difficult to treat due its resistance both radiation and chemotherapy. This largely the unique biology GBM cells, which can evade effects conventional treatments through mechanisms such as increased cell death rapid regeneration cancerous cells. Additionally, blood–brain barrier makes it for chemotherapy drugs reach leading reduced effectiveness. Despite these challenges, there are several treatment options available GBM. The standard care newly diagnosed patients involves surgical resection followed by concurrent chemoradiotherapy adjuvant Emerging include immunotherapy, checkpoint inhibitors, targeted therapies, bevacizumab, attempt attack specific vulnerabilities in Another promising approach use tumor-treating fields, type electric field therapy has been shown slow growth Clinical trials ongoing evaluate safety efficacy other innovative GBM, intending improve with outcomes patients.

Language: Английский

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Molecular mechanism of VEGF and its role in pathological angiogenesis

Journal of Cellular Biochemistry, Journal Year: 2022, Volume and Issue: 123(12), P. 1938 - 1965

Published: Oct. 26, 2022

Abstract Over the last seven decades, a significant scientific contribution took place in delineation of implications vascular endothelial‐derived growth factor (VEGF) processes angiogenesis. Under pathological conditions, mainly response to hypoxia or ischemia, elevated VEGF levels promote damage and abnormal blood vessels. Indeed, development biology has revolutionized our understanding its role conditions. Hence, targeting VEGF‐mediated molecular pathways could be an excellent therapeutic strategy for managing cancers intraocular neovascular disorders. Although anti‐VEGF therapies, such as monoclonal antibodies small‐molecule tyrosine kinase inhibitors, have limited clinical efficacy, they can still significantly improve overall survival rate. This thus demands further investigation through alternative strategies management review article focuses on recent developments toward functional tumor eye pathologies. Moreover, angiogenesis, exciting frontier treatment ischemic disorders, is highlighted this review, including wound healing.

Language: Английский

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Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy

Molecular Biomedicine, Journal Year: 2022, Volume and Issue: 3(1)

Published: March 4, 2022

Abstract Triple negative breast cancer (TNBC) is a subtype of cancer, with estrogen receptor, human epidermal growth factor receptor 2 and progesterone negative. TNBC characterized by high heterogeneity, rates metastasis, poor prognosis, lack therapeutic targets. Now the treatment still based on surgery chemotherapy, which effective only in initial stage but almost useless advanced stage. And due to hormone target, hormonal therapies have little beneficial effects. In recent years, signaling pathways receptor-specific targets been reported be patients under specific clinical conditions. targeted approved for many other cancers even subtypes options are limited. Most showed no response, may related heterogeneity TNBC, therefore more treatments predictive biomarkers needed. present review, we summarize potential opinions dysregulated receptors pathways, play significant role multiple stages development. We also focus application immunotherapy preclinical trials therapy TNBC. hope accelerate research development new drugs understanding relevant mechanisms, improve survival.

Language: Английский

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Receptor tyrosine kinase inhibitors in cancer

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(4)

Published: March 22, 2023

Language: Английский

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Targeted therapy for osteosarcoma: a review

Journal of Cancer Research and Clinical Oncology, Journal Year: 2023, Volume and Issue: 149(9), P. 6785 - 6797

Published: Feb. 18, 2023

Language: Английский

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Therapeutic advances of targeting receptor tyrosine kinases in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 14, 2024

Abstract Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression certain RTKs, are critical creating environments conducive tumor development. Following discovery, extensive research has revealed how RTK dysregulation contributes oncogenesis, with many subtypes showing dependency on aberrant signaling for proliferation, survival progression. These findings paved the way targeted therapies that aim inhibit crucial biological pathways cancer. As result, RTKs emerged as primary targets anticancer therapeutic Over past two decades, this led synthesis validation numerous small molecule kinase inhibitors (TKIs), now effectively utilized treating various types. In manuscript we provide comprehensive understanding context We explored alterations specific receptors across different malignancies, special dedicated examination current inhibitors, highlighting potential therapies. By integrating latest evidence, seek elucidate pivotal biology efficacy inhibition promising treatment outcomes.

Language: Английский

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Advances in pyrazolo[1,5-a]pyrimidines: synthesis and their role as protein kinase inhibitors in cancer treatment

RSC Advances, Journal Year: 2025, Volume and Issue: 15(5), P. 3756 - 3828

Published: Jan. 1, 2025

Pyrazolo[1,5- a ]pyrimidines are notable class of heterocyclic compounds with potent protein kinase inhibitor (PKI) activity, playing critical role in targeted cancer therapy.

Language: Английский

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