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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Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches

Molecules, Journal Year: 2022, Volume and Issue: 27(17), P. 5730 - 5730

Published: Sept. 5, 2022

Prostate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in globally. Patients affected with prostate present either a localized or advanced disease. In this review, we aim provide holistic overview cancer, including diagnosis disease, mutations leading onset progression treatment options. diagnoses include digital rectal examination, prostate-specific antigen analysis, biopsies. Mutations certain genes are linked onset, progression, metastasis cancer. Treatment for encompasses active surveillance, ablative radiotherapy, radical prostatectomy. Men who relapse metastatic receive androgen deprivation therapy (ADT), salvage chemotherapy. Currently, available options more effective when used as combination therapy; however, despite options, remains be incurable. There has been ongoing research on finding identifying other approaches such use traditional medicine, application nanotechnologies, gene combat drug resistance, well reduce adverse effects come current article, summarize involved alternative

Language: Английский

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Targeting epigenetic regulators to overcome drug resistance in cancers

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

Published: Feb. 17, 2023

Abstract Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic mechanisms, DNA methylation, histone modification, non-coding RNA have been well studied. Increasing evidence has shown that aberrant regulations contribute to tumor resistance. Therefore, targeting regulators represents an effective strategy reverse drug In this review, we summarize roles addition, as essential factors modifications, demethylases mediate or genomic modifications. Herein, comprehensively describe functions demethylase family including lysine-specific family, Jumonji C-domain-containing arginine fully discuss their regulatory mechanisms related therapeutic strategies, small-molecule inhibitors small interfering overcome resistance, are also described.

Language: Английский

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Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends

Journal of Biomedical Science, Journal Year: 2021, Volume and Issue: 28(1)

Published: April 11, 2021

Abstract Epigenetic drug discovery field has evidenced significant advancement in the recent times. A plethora of small molecule inhibitors have progressed to clinical stage investigations and are being explored exhaustively ascertain conclusive benefits diverse malignancies. Literature precedents indicates that substantial amount efforts were directed towards use epigenetic tools monotherapy as well combination regimens at level, however, preclinical/preliminary explorations inclined identification prudent approaches can leverage anticancer potential single agents only. This review article presents an update FDA approved drugs along with undergoing different cancer types. detailed discussion pragmatic strategies expected steer progress therapy through implementation emerging such PROTACS CRISPR/Cas9 logical ways for scaffold fabrication selectively approach enzyme isoforms pursuit garnering amplified antitumor effects been covered. In addition, compilation also rational construction multi-targeting assemblages employing previously identified pharmacophores alternatives therapy.

Language: Английский

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The long and short non-coding RNAs modulating EZH2 signaling in cancer

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 2, 2022

Non-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate developmental and biological processes their abnormal expression affects cancer progression. These can function as upstream mediators different signaling pathways enhancer zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs exert functional roles cells due its methyltransferase activity. gene via inducing H3K27me3. In the present review, our aim provide mechanistic discussion ncRNAs role regulating cancers. MiRNAs dually induce/inhibit affect downstream targets such Wnt, STAT3 EMT. Furthermore, miRNAs regulate therapy response affecting signaling. It noteworthy that reduce miRNA by binding promoter exerting Small-interfering (siRNA) short-hairpin (shRNA) synthetic, short capable reducing suppressing LncRNAs mainly targeting miRNAs. lncRNAs induce modulating expression. Circular (CircRNAs), like lncRNAs, areas discussed review focus on molecular leading clinical translation.

Language: Английский

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Tazemetostat: EZH2 Inhibitor

Journal of the Advanced Practitioner in Oncology, Journal Year: 2022, Volume and Issue: 13(2), P. 158 - 163

Published: March 1, 2022

Epigenetic regulation is a novel approach to cancer treatment. Inhibition of enhancer zeste homolog 2 (EZH2) method provide targeted epigenetic regulation. Tazemetostat first-in-class regulator that specifically inhibits EZH2. This new FDA-approved oral treatment received accelerated approval for patients with hematologic and solid malignancies. was first approved 16 years older metastatic or locally advanced epithelioid sarcoma not eligible complete resection based on the results an international open-label phase II basket trial. Another multicenter trial led relapsed refractory follicular lymphoma EZH2 mutation who have at least two prior systemic therapies no satisfactory alternative options. as inhibitor provides effective tolerable option these patients.

Language: Английский

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Cancer epigenetics: from laboratory studies and clinical trials to precision medicine

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 15, 2024

Abstract Epigenetic dysregulation is a common feature of myriad human diseases, particularly cancer. Defining the epigenetic defects associated with malignant tumors has become focus cancer research resulting in gradual elucidation cell regulation. In fact, most stages tumor progression, including tumorigenesis, promotion, and recurrence are accompanied by alterations, some which can be reversed drugs. The main objective therapy era personalized precision medicine to detect biomarkers improve risk assessment, diagnosis, targeted treatment interventions. Rapid technological advancements streamlining characterization molecular changes cancers have propelled drug development. This review summarizes mechanisms discusses past present examples inhibitors diagnosis treatment, an emphasis on development enzyme or final part, prospect precise considered based better understanding abnormalities

Language: Английский

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Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(11), P. 1049 - 1082

Published: Oct. 20, 2022

Reversible, spatial, and temporal regulation of metabolic reprogramming epigenetic homeostasis are prominent hallmarks carcinogenesis. Cancer cells reprogram their metabolism to meet the high bioenergetic biosynthetic demands for vigorous proliferation. Epigenetic dysregulation is a common feature human cancers, which contributes tumorigenesis maintenance malignant phenotypes by regulating gene expression. The epigenome sensitive changes. Metabolism produces various metabolites that substrates, cofactors, or inhibitors enzymes. Alterations in pathways fluctuations intermediate convey information regarding intracellular status into nucleus modulating activity enzymes thus remodeling landscape, inducing transcriptional responses heterogeneous requirements. regulated machinery at both post-transcriptional levels. modifiers, chromatin remodelers non-coding RNAs integral contributors regulatory networks involved cancer metabolism, facilitating transformation. However, significance close connection between epigenetics context has not been fully deciphered. Thus, it will be constructive summarize update emerging new evidence supporting this bidirectional crosstalk deeply assess how abnormalities could exploited optimize treatment paradigms establish therapeutic options. In review, we central mechanisms reciprocally modulate each other elaborate upon major contributions interplays aberrations rewiring initiation development. Finally, highlight potential opportunities hematological malignancies solid tumors targeting epigenetic-metabolic circuit. summary, endeavored depict current understanding coordination these fundamental more comprehensively provide perspectives utilizing targets treatment.

Language: Английский

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Small cell lung cancer transformation: From pathogenesis to treatment

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 595 - 606

Published: March 8, 2022

Language: Английский

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Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 8, 2024

Abstract Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, exploration of emerging modalities such as immunotherapy integration medicine engineering technology therapy, efficacy these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny inhibitory milieu within GBM has underscored significance cellular constituents microenvironment their interactions with cells neurons. Novel immune targeted therapy strategies have emerged, offering promising avenues for advancing treatment. One pivotal mechanism orchestrating immunosuppression involves aggregation myeloid-derived suppressor (MDSCs), glioma-associated macrophage/microglia (GAM), regulatory T (Tregs). Among these, MDSCs, though constituting minority (4–8%) CD45 + GBM, play central component fostering evasion propelling tumor progression, angiogenesis, invasion, metastasis. MDSCs deploy intricate mechanisms that adapt dynamic (TME). Understanding interplay between provides compelling basis This review seeks elucidate inherent explore existing targets, consolidate insights into MDSC induction contribution immunosuppression. Additionally, comprehensively surveys ongoing clinical trials potential strategies, envisioning future where targeting could reshape landscape GBM. Through synergistic other modalities, this approach can establish multidisciplinary, multi-target paradigm, ultimately improving prognosis quality life patients

Language: Английский

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