Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Окт. 8, 2022

Abstract The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, gene therapy products) have approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 these were identified cancer therapeutics cancer-related drugs, 120 them classified therapeutic for solid tumors according to their initial indications. These evolved from small molecules with broad-spectrum antitumor properties early stage monoclonal antibodies (mAbs) antibody‒drug conjugates (ADCs) more precise targeting effect during most recent decade. extended indications other malignancies, constituting treatment system monotherapy combined therapy. However, available targets are still mainly limited receptor tyrosine kinases (RTKs), restricting development drugs. In this review, summarized indications, characteristics, functions. Additionally, RTK-targeted therapies immune checkpoint-based immunotherapies also discussed. Our analysis existing challenges potential opportunities may advance tumor future.

Язык: Английский

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Therapeutic potential of pyrrole and pyrrolidine analogs: an update

Molecular Diversity, Год журнала: 2022, Номер 26(5), С. 2915 - 2937

Опубликована: Янв. 25, 2022

Язык: Английский

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Cellular senescence and the tumour microenvironment

Molecular Oncology, Год журнала: 2022, Номер 16(18), С. 3333 - 3351

Опубликована: Июнь 8, 2022

The senescence-associated secretory phenotype (SASP), where senescent cells produce a variety of secreted proteins including inflammatory cytokines, chemokines, matrix remodelling factors, growth factors and so on, plays pivotal but varying roles in the tumour microenvironment. effects SASP on surrounding microenvironment depend cell type process cellular senescence induction, which is often associated with innate immunity. Via SASP-mediated paracrine effects, can remodel tissues by modulating character adjacent cells, such as stromal, immune well cancer cells. both tumour-suppressive tumour-promoting observed surveillance (tumour-suppressive) suppression anti-tumour immunity most cancer-associated fibroblasts T (tumour-promoting). In this review, we discuss features emphasis their context-dependency that determines whether they promote or suppress development. Potential usage recently developed drugs (senomorphics) selectively kill (senolytics) therapy are also discussed.

Язык: Английский

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Small molecule inhibitors targeting the cancers

MedComm, Год журнала: 2022, Номер 3(4)

Опубликована: Окт. 13, 2022

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary therapies for cancer. Due to their advantages a wide range targets, convenient medication, ability penetrate into central nervous system, many efforts have been devoted developing more small inhibitors. To date, 88 approved by United States Food Drug Administration treat cancers. Despite remarkable progress, cancer treatment still face obstacles, such as low response rate, short duration response, toxicity, biomarkers, resistance. better promote development targeting cancers, we comprehensively reviewed involved all agents pivotal drug candidates clinical trials arranged signaling pathways classification We discussed lessons learned from these agents, proper strategies overcome resistance arising different mechanisms, combination concerned Through our review, hoped provide insights perspectives research treatment.

Язык: Английский

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Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

The Lancet Oncology, Год журнала: 2023, Номер 24(6), С. 646 - 657

Опубликована: Май 11, 2023

Язык: Английский

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Targeting Breast Cancer: An Overlook on Current Strategies

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 3643 - 3643

Опубликована: Фев. 11, 2023

Breast cancer (BC) is one of the most widely diagnosed cancers and a leading cause death among women worldwide. Globally, BC second frequent first gynecological one, affecting with relatively low case-mortality rate. Surgery, radiotherapy, chemotherapy are main treatments for BC, even though latter often not aways successful because common side effects damage caused to healthy tissues organs. Aggressive metastatic BCs difficult treat, thus new studies needed in order find therapies strategies managing these diseases. In this review, we intend give an overview field, presenting data from literature concerning classification drugs used therapy treatment BCs, along clinical studies.

Язык: Английский

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The CDK inhibitor AT7519 inhibits human glioblastoma cell growth by inducing apoptosis, pyroptosis and cell cycle arrest

Cell Death and Disease, Год журнала: 2023, Номер 14(1)

Опубликована: Янв. 9, 2023

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor with a poor median survival of less than 15 months. However, clinical strategies and effective therapies are limited. Here, we found that second-generation small molecule multi-CDK inhibitor AT7519 potential drug for GBM treatment according to high-throughput screening via Approved Drug Library Clinical Compound (2718 compounds). We significantly inhibited cell viability proliferation U87MG, U251, patient-derived cells in dose-dependent manner. Furthermore, also phosphorylation CDK1/2 arrested cycle at G1-S G2-M phases. More importantly, induced intrinsic apoptosis pyroptosis caspase-3-mediated cleavage gasdermin E (GSDME). In glioblastoma intracranial subcutaneous xenograft assays, volume was reduced after AT7519. summary, induces death through multiple pathways inhibits growth, indicating chemical available treatment.

Язык: Английский

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Revolutionizing cancer care strategies: immunotherapy, gene therapy, and molecular targeted therapy

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Янв. 28, 2024

Abstract Despite the availability of technological advances in traditional anti-cancer therapies, there is a need for more precise and targeted cancer treatment strategies. The wide-ranging shortfalls conventional anticancer therapies such as systematic toxicity, compromised life quality, limited to severe side effects are major areas concern approaches. Owing expansion knowledge advancements field biology, innovative safe anti-cancerous approaches immune therapy, gene therapy rapidly evolving with aim address limitations therapies. concept immunotherapy began capability coley toxins stimulate toll-like receptors cells provoke an response against cancers. With in-depth understating molecular mechanisms carcinogenesis their relationship disease prognosis, approaches, that inhibit or specific cancer-promoting cancer-inhibitory molecules respectively, have offered promising outcomes. In this review, we evaluate achievement challenges these technically advanced presenting overall progress perspective each approach.

Язык: Английский

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A Review of Approaches to Potentiate the Activity of Temozolomide against Glioblastoma to Overcome Resistance

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3217 - 3217

Опубликована: Март 12, 2024

A glioblastoma (GBM) is one of the most aggressive, infiltrative, and treatment-resistant malignancies central nervous system (CNS). The current standard care for GBMs include maximally safe tumor resection, followed by concurrent adjuvant radiation treatment chemotherapy with DNA alkylating agent temozolomide (TMZ), which was approved FDA in 2005 based on a marginal increase (~2 months) overall survival (OS) levels. This approach, while initially successful containing treating GBM, almost invariably fails to prevent recurrence. In addition limited therapeutic benefit, TMZ also causes debilitating adverse events (AEs) that significantly impact quality life GBM patients. Some common AEs hematologic (e.g., thrombocytopenia, neutropenia, anemia) non-hematologic nausea, vomiting, constipation, dizziness) toxicities. Recurrent are often resistant other DNA-damaging agents. Thus, there an urgent need devise strategies potentiate activity, overcome drug resistance, reduce dose-dependent AEs. Here, we analyze major mechanisms resistance-mediated intracellular signaling activation repair pathways overexpression transporters. We review some approaches investigated counteract these resistance TMZ, including use chemosensitizers delivery enhance tumoral exposure.

Язык: Английский

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CDK4 selective inhibition improves preclinical anti-tumor efficacy and safety

Cancer Cell, Год журнала: 2025, Номер 43(3), С. 464 - 481.e14

Опубликована: Март 1, 2025

Highlights•Atirmociclib (PF-07220060) is a next-generation CDK4 selective inhibitor•Impact reduction on neutrophils was in proportion to increase selectivity•Greater target coverage results deeper anti-tumor responses•Combinatorial agents further atirmociclib efficacySummaryCDK4/6 inhibitors have revolutionized treatment of hormone receptor positive (HR+), HER2 non-amplified (HER2−) breast cancer. Yet, all "dual" CDK4/6 show common dose-limiting hematologic toxicities, foremost neutropenia. This poses challenges provide these at concentrations necessary extinguish cell cycling tumors. HR+ cancer cells are highly dependent but not CDK6. By contrast, dispensable for human bone marrow derived cells, due the primary and compensatory role CDK6 hematopoiesis. prompted us develop (PF-07220060), inhibitor. Atirmociclib's impact circulating reduced, with its versus selectivity. Realized dose intensification led greater inhibition responses, pointing as limiting factor inhibitor efficacy. We also highlight combinatorial that may counter acquired resistance widen clinical application.Graphical abstract

Язык: Английский

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