Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 28, 2023

Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel LAG-3 drugs have also been approved clinical application. With the widespread use of drug, we must deeply analyze dilemma agents seek a breakthrough treatment prospect. Over past decades, these demonstrated dramatic efficacy, especially patients with melanoma non-small cell lung cancer (NSCLC). Nonetheless, field broad concept solid tumours, non-specific indications, inseparable immune response side effects, unconfirmed progressive disease, complex regulatory networks resistance are four barriers that limit its Fortunately, successful trials ICB combination therapies, advent era oncolytic virus gene editing, technical mRNA vaccines nano-delivery systems made remarkable breakthroughs currently. In this review, enumerate mechanisms each checkpoint targets, associations between tumour mutation burden, key or signalling pathways, specific evidence efficacy classical targets new among different types put forward dialectical thoughts on drug safety. Finally, discuss importance accurate triage based recent advances predictive biomarkers diagnostic testing techniques.

Language: Английский

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Properties of FDA-approved small molecule protein kinase inhibitors: A 2023 update

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106552 - 106552

Published: Nov. 17, 2022

Owing to the dysregulation of protein kinase activity in many diseases including cancer, this enzyme family has become one most important drug targets 21st century. There are 72 FDA-approved therapeutic agents that target about two dozen different kinases and three these drugs were approved 2022. Of drugs, twelve protein-serine/threonine kinases, four directed against dual specificity (MEK1/2), sixteen block nonreceptor protein-tyrosine 40 receptor kinases. The data indicate 62 prescribed for treatment neoplasms (57 solid tumors breast, lung, colon, ten nonsolid such as leukemia, both tumors: acalabrutinib, ibrutinib, imatinib, midostaurin). Four (abrocitinib, baricitinib, tofacitinib, upadacitinib) used inflammatory (atopic dermatitis, psoriatic arthritis, rheumatoid Crohn disease, ulcerative colitis). eighteen multiple diseases. following received FDA approval 2022 specified diseases: abrocitinib dermatitis), futibatinib (cholangiocarcinomas), pacritinib (myelofibrosis). All orally effective with exception netarsudil, temsirolimus, trilaciclib. This review summarizes physicochemical properties all small molecule inhibitors lipophilic efficiency ligand efficiency.

Language: Английский

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Properties of FDA-approved small molecule protein kinase inhibitors: A 2024 update

Pharmacological Research, Journal Year: 2024, Volume and Issue: 200, P. 107059 - 107059

Published: Jan. 11, 2024

Owing to the dysregulation of protein kinase activity in many diseases including cancer, this enzyme family has become one most important drug targets 21st century. There are 80 FDA-approved therapeutic agents that target about two dozen different kinases and seven these drugs were approved 2023. Of drugs, thirteen protein-serine/threonine kinases, four directed against dual specificity (MEK1/2), twenty block nonreceptor protein-tyrosine 43 inhibit receptor kinases. The data indicate 69 prescribed for treatment neoplasms. Six (abrocitinib, baricitinib, deucravacitinib, ritlecitinib, tofacitinib, upadacitinib) used inflammatory (atopic dermatitis, rheumatoid arthritis, psoriasis, alopecia areata, ulcerative colitis). nearly multiple diseases. following received FDA approval 2023: capivasertib (HER2-positive breast cancer), fruquintinib (metastatic colorectal momelotinib (myelofibrosis), pirtobrutinib (mantle cell lymphoma, chronic lymphocytic leukemia, small lymphoma), quizartinib (Flt3-mutant acute myelogenous leukemia), repotrectinib (ROS1-positive lung ritlecitinib (alopecia areata). All orally effective with exception netarsudil, temsirolimus, trilaciclib. This review summarizes physicochemical properties all molecule inhibitors molecular weight, number hydrogen bond donors/acceptors, polar surface area, potency, solubility, lipophilic efficiency, ligand efficiency.

Language: Английский

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Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Nov. 28, 2023

The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. formation is multifaceted process influenced by genetic, epigenetic, and environmental factors. offer distinctive platform investigating the origin cancer, paving way novel approaches to treatment, drug testing, tailored medical interventions. This review article will provide an overview science behind iPSCs, current limitations challenges iPSC-based therapy, ethical social implications, comparative analysis with other types also discuss applications tumorigenesis, future tumorigenesis highlight successful case studies utilizing research. conclusion summarize advancements made research importance continued investment iPSC unlock full potential these cells.

Language: Английский

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Emerging Therapeutic Strategies to Overcome Drug Resistance in Cancer Cells

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2478 - 2478

Published: July 7, 2024

The rise of drug resistance in cancer cells presents a formidable challenge modern oncology, necessitating the exploration innovative therapeutic strategies. This review investigates latest advancements overcoming mechanisms employed by cells, focusing on emerging modalities. intricate molecular insights into resistance, including genetic mutations, efflux pumps, altered signaling pathways, and microenvironmental influences, are discussed. Furthermore, promising avenues offered targeted therapies, combination treatments, immunotherapies, precision medicine approaches highlighted. Specifically, synergistic effects combining traditional cytotoxic agents with molecularly inhibitors to circumvent pathways examined. Additionally, evolving landscape immunotherapeutic interventions, immune checkpoint adoptive cell is explored terms bolstering anti-tumor responses evasion mechanisms. Moreover, significance biomarker-driven strategies for predicting monitoring treatment underscored, thereby optimizing outcomes. For future direction paradigms, current focused prevailing challenges improving patient outcomes, through an integrative analysis these

Language: Английский

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Recent advances in biological and medicinal profile of schiff bases and their metal complexes: An updated version (2018–2023)

Results in Chemistry, Journal Year: 2024, Volume and Issue: 7, P. 101350 - 101350

Published: Jan. 1, 2024

Schiff bases are most the widely used class of molecules in organic as well inorganic chemistry and known for fabricating stable metal complexes. their complexes utilized pharmaceutically medicinally important scaffolds because versatile biological profile. So herein, this review, we summarized recently developed biologically active with V, Fe, Co, Ni, Cu, Zn, Zr, Rh, Pd, Cd, Sn, Ir, Pt, Pb metals. The anti-bacterial, anti-fungal, anti-viral, anti-microbial, anti-cancer, corrosion inhibiting studies have been compiled present review. Anti-bacterial activities has described against both gram-positive (S. aureus, B. subtilis) gram-negative (E. coli, proteus) bacteria. anti-fungal action various Candida albicans, tropicalis, glabrata, Aspergillusniger, other fungal strains included. in-vitro anti-viral examination in-silico evaluation main protease (MPro) protein SARS-CoV-2 virus (PDB ID: 7BZ5, 6LU7, 7C8U), chikungunya nsP4 4RY5) HIV-1 6MQA) also summarized. Additionally, results cytotoxic properties cell lines including MCF-7, HeLa, HCT116, Dalton's Lymphoma, SGC-7901, BGC-823, HEK-293, HEPG2, DU-145 discussed. Thus ultimately, review highlights recent development (2018–2023) base potency strains.

Language: Английский

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Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 984 - 984

Published: Feb. 28, 2024

Anticancer drugs induce apoptotic and non-apoptotic cell death in various cancer types. The signaling pathways for anticancer drug-induced have been shown to differ between drug-sensitive drug-resistant cells. In atypical multidrug-resistant leukemia cells, the c-Jun/activator protein 1 (AP-1)/p53 pathway leading is altered. Cancer cells treated with undergo c-Jun/AP-1–mediated are involved c-Jun N-terminal kinase activation growth arrest- DNA damage-inducible gene 153 (Gadd153)/CCAAT/enhancer-binding homologous induction, regardless of p53 genotype. Gadd153 induction associated mitochondrial membrane permeabilization after drug treatment involves a coupled endoplasmic reticulum stress response. apoptosis by mediated intrinsic (cytochrome c, Cyt c) subsequent caspase cascade via proapoptotic genes (e.g., Bax Bcl-xS) their interactions. caspase-dependent caspase-independent occurs extrinsic pathways. targeting antiapoptotic such as Bcl-2 enhances efficacy. modulation Bcl-xS transduction increases sensitivity multidrug resistance-related protein-overexpressing epidermoid carcinoma drugs. significance autophagy therapy remains be elucidated. this review, we summarize current knowledge death-related alterations during discuss potential strategies enhance

Language: Английский

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Injecting hope: the potential of intratumoral immunotherapy for locally advanced and metastatic cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Despite enormous progress, advanced cancers are still one of the most serious medical problems in current society. Although various agents and therapeutic strategies with anticancer activity known used, they often fail to achieve satisfactory long-term patient outcomes survival. Recently, immunotherapy has shown success patients by harnessing important interactions between immune system cancer. However, many these therapies lead frequent side effects when administered systemically, prompting treatment modifications or discontinuation or, severe cases, fatalities. New approaches like intratumoral immunotherapy, characterized reduced effects, cost, systemic toxicity, offer promising prospects for future applications clinical oncology. In context locally metastatic cancer, combining diverse immunotherapeutic other targeting multiple cancer hallmarks appears crucial. Such combination hold promise improving survival promoting a sustained response. This review aims provide overview approaches, specifically focusing on administration drugs cancers. It also explores integration modalities maximize Additionally, summarizes recent advances discusses novel outlining directions field.

Language: Английский

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Insights into tumor-derived exosome inhibition in cancer therapy

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 285, P. 117278 - 117278

Published: Jan. 13, 2025

Language: Английский

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Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 15, 2025

The efficacy of cancer immunotherapy relies on a sufficient amount functional immune cells. Triple-negative breast lacks enough cell infiltration, and adjuvant therapy is necessary to prime anti-tumor immunity. However, the improvement in unsatisfactory with concern about inducing systemic immunotoxicity. Herein, we create an abemaciclib-loaded supramolecular peptide hydrogel formed by peptide-drug amphiphiles for neoadjuvant triple-negative cancer, where amphiphile conjugate β-sheet-forming 1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethanol (NLG919), inhibitor indoleamine 2,3-dioxygenase 1. can be injected into tumor site retained at least one week sustained release both abemaciclib NLG919. able induce immunogenic death cells increase interleukin-2 secretion cytotoxic T lymphocytes. Abemaciclib adversely upregulates 1, whose kynurenine production activity inhibited reduces recurrence pulmonary metastasis prolongs survival animals. This provides potential platform reduced toxicity compared free abemaciclib. recruited. Here this group designs achieving after intratumoral injection effectively IL-2 secretion, thereby exerting cancer.

Language: Английский

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