Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 15, 2024

Abstract Cancer is a major public health problem worldwide with more than an estimated 19.3 million new cases in 2020. The occurrence rises dramatically age, and the overall risk accumulation combined tendency for cellular repair mechanisms to be less effective older individuals. Conventional cancer treatments, such as radiotherapy, surgery, chemotherapy, have been used decades combat cancer. However, emergence of novel fields research has led exploration innovative treatment approaches focused on immunotherapy, epigenetic therapy, targeted multi-omics, also multi-target therapy. hypothesis was based that drugs designed act against individual targets cannot usually battle multigenic diseases like Multi-target therapies, either combination or sequential order, recommended acquired intrinsic resistance anti-cancer treatments. Several studies multi-targeting treatments due their advantages include; overcoming clonal heterogeneity, lower multi-drug (MDR), decreased drug toxicity, thereby side effects. In this study, we'll discuss about drugs, benefits improving recent advances field multi-targeted drugs. Also, we will study performed clinical trials using therapeutic agents treatment.

Язык: Английский

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Therapeutic advances of targeting receptor tyrosine kinases in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 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.

Язык: Английский

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Liquid biopsy for human cancer: cancer screening, monitoring, and treatment

MedComm, Год журнала: 2024, Номер 5(6)

Опубликована: Май 28, 2024

Currently, tumor treatment modalities such as immunotherapy and targeted therapy have more stringent requirements for obtaining growth information require accurate easy-to-operate detection methods. Compared with traditional tissue biopsy, liquid biopsy is a novel, minimally invasive, real-time tool detecting directly or indirectly released by tumors in human body fluids, which suitable the of new modalities. Liquid has not been widely used clinical practice, there are fewer reviews related applications. This review summarizes applications components (e.g., circulating cells, DNA, extracellular vesicles, etc.) tumorigenesis progression. includes development process techniques biopsies, early screening tumors, detection, guiding therapeutic strategies (liquid biopsy-based personalized medicine prediction response). Finally, current challenges future directions proposed. In sum, this will inspire researchers to use technology promote realization individualized therapy, improve efficacy provide better options patients.

Язык: Английский

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Journey of PROTAC: From Bench to Clinical Trial and Beyond

Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Proteolysis-targeting chimeras (PROTACs) represent a transformative advancement in drug discovery, offering method to degrade specific intracellular proteins. Unlike traditional inhibitors, PROTACs are bifunctional molecules that target proteins for elimination, enabling the potential treatment of previously "undruggable" This concept, pioneered by Crews and his team, introduced use small link protein an E3 ubiquitin ligase, inducing ubiquitination subsequent degradation protein. By promoting rather than merely inhibiting function, present novel therapeutic strategy with enhanced specificity effectiveness, especially areas such as cancer neurodegenerative diseases. Since their initial field PROTAC research has rapidly expanded numerous now designed wide range disease-relevant The substantial research, investment, collaboration across academia pharmaceutical industry reflect growing interest PROTACs. Review discusses journey from discovery clinical trials, highlighting advancements challenges. Additionally, recent developments fluorescent photogenic PROTACs, used real-time tracking degradation, presented, showcasing evolving targeted therapy.

Язык: Английский

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Model-informed precision dosing: State of the art and future perspectives

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 215, С. 115421 - 115421

Опубликована: Авг. 17, 2024

Model-informed precision dosing (MIPD) stands as a significant development in personalized medicine to tailor drug individual patient characteristics. MIPD moves beyond traditional therapeutic monitoring (TDM) by integrating mathematical predictions of dosing, and considering patient-specific factors (patient characteristics, measurements) well different sources variability. For this purpose, rigorous model qualification is required for the application patients. This review delves into new methods selection validation, also highlighting role machine learning improving MIPD, utilization biosensors real-time monitoring, potential models biomarkers efficacy or toxicity dosing. The clinical evidence TDM discussed various medical fields including infection medicine, oncology, transplant inflammatory bowel diseases, thereby underscoring pharmacokinetics/pharmacodynamics specific biomarkers. Further research, particularly randomized trials, warranted corroborate value enhancing outcomes advancing medicine.

Язык: Английский

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CAR-based immunotherapy for breast cancer: peculiarities, ongoing investigations, and future strategies

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 12, 2024

Surgery, chemotherapy, and endocrine therapy have improved the overall survival postoperative recurrence rates of Luminal A, B, HER2-positive breast cancers but treatment modalities for triple-negative cancer (TNBC) with poor prognosis remain limited. The effective application rapidly developing chimeric antigen receptor (CAR)-T cell in hematological tumors provides new ideas cancer. Choosing suitable specific targets is crucial applying CAR-T treatment. In this paper, we summarize therapy’s potential different subtypes based on existing research progress, especially TNBC. CAR-based immunotherapy has resulted advancements CAR-macrophages, CAR-NK cells, CAR-mesenchymal stem cells (MSCs) may be more safer treating solid tumors, such as However, tumor microenvironment (TME) side effects pose challenges to immunotherapy. cells-derived exosomes are advantageous therapy. Exosomes carrying CAR immense value provide a modality good effects. review, an overview development discuss progress CAR-expressing We elaborate TNBC prospects using CAR-MSCs

Язык: Английский

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Theranostic Uses of the Heme Pathway in Neuro-Oncology: Protoporphyrin IX (PpIX) and Its Journey from Photodynamic Therapy (PDT) through Photodynamic Diagnosis (PDD) to Sonodynamic Therapy (SDT)

Cancers, Год журнала: 2024, Номер 16(4), С. 740 - 740

Опубликована: Фев. 10, 2024

ALA PDT, first approved as a topical therapy to treat precancerous skin lesions in 1999, targets the heme pathway selectively cancers. When provided with excess ALA, fluorescent photosensitizer PpIX accumulates primarily cancer tissue, and PDD is used identify bladder brain cancers visual aid for surgical resection. PDT has shown promising anecdotal clinical results recurrent glioblastoma multiforme. SDT represents noninvasive way activate potential achieve success treatment of both intracranial extracranial This review describes creation evolution from malignant tumors and, most recently, into form SDT. Current trials high-grade gliomas adults, pediatric trial lethal brainstem cancer, diffuse intrinsic pontine glioma (DIPG), are also described.

Язык: Английский

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Risk Factors Analysis of Cutaneous Adverse Drug Reactions Caused by Targeted Therapy and Immunotherapy Drugs for Oncology and Establishment of a Prediction Model

Clinical and Translational Science, Год журнала: 2025, Номер 18(1)

Опубликована: Янв. 1, 2025

Targeted therapy and immunotherapy drugs for oncology have greater efficacy tolerability than cytotoxic chemotherapeutic drugs. However, the cutaneous adverse drug reactions associated with these newer therapies are more common remain poorly predicted. An effective prediction model is urgently needed essential. This retrospective study included 1052 patients, divided into train set, test external validation set. As a data-driven study, total of 76 variables were collected. Univariate logistic analysis, least absolute shrinkage selection operator regression, stepwise regression utilized feature screening. Finally, nine machine-learning models constructed compared, grid search was performed to adjust parameters. Model performance evaluated using calibration curve area under receiver operating characteristic (AUROC). Nine risk factors eventually identified: age, treatment modality, cancer types, history allergies, age-corrected Charlson comorbidity index, percentage eosinophils, number monocytes, Eastern Cooperative Oncology Group Performance Status, C-reactive protein. Among models, best, demonstrating strong in set (AUROC = 0.734) 0.817). identified significant developed nomogram model. These findings important implications optimizing therapeutic maintaining quality life patients from perspective managing reactions. Trial Registration: ChiCTR2400088422.

Язык: Английский

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A novel imatinib analogue inhibitor of chronic myeloid leukaemia: design, synthesis and characterization—explanation of its folded conformation

Royal Society Open Science, Год журнала: 2025, Номер 12(1)

Опубликована: Янв. 1, 2025

Chronic myeloid leukaemia (CML) is primarily treated using imatinib mesylate, a tyrosine kinase inhibitor (TKI) targeting the BCR::ABL1 oncoprotein. However, development of drug resistance and adverse side effects necessitate exploration alternative therapeutic agents. This study presents synthesis characterization novel analogue, 3-chloro-N-(2-methyl-5-((4-(pyridin-2-yl)pyrimidin-2-yl)amino)phenyl)benzamide (PAPP1). The compound's structure was elucidated X-ray crystallography spectroscopic techniques, including NMR, infrared UV-visible. Crystallographic analysis reveals that PAPP1 consists phenyl-amino-pyridine-pyrimidine (PAPP) scaffold with substituted aromatic rings forming nearly coplanar geometry. Additionally, supramolecular interactions in crystal are mediated by hydrogen bonds dispersion forces, dimers layered structures. Molecular docking studies demonstrate strong binding affinity to ABL1 enzyme, showing comparable energy imatinib, indicating its potential as lead compound for further development. Computational studies, molecular electrostatic vibrational analysis, provide support structural stability bioactivity PAPP1. These findings suggest PAPP could be promising future CML design, offering existing TKIs, susceptible optimization.

Язык: Английский

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Versatile New Lanthanide Complexes Containing Organic Ligand Derived From Vitamin B6 as Potential Tyrosinase Inhibitors: Synthesis, Characterizations, and Structure Activity Investigations

Applied Organometallic Chemistry, Год журнала: 2025, Номер 39(3)

Опубликована: Янв. 30, 2025

ABSTRACT The synthesis, characterizations, and tyrosinase enzyme inhibition experiments on eight novel lanthanide metal complexes ( 1 – 8 ) are reported. A multidonor versatile ligand L was prepared from the condensation reaction of picolinohydrazide with pyridoxal. synthesized were analyzed using FT‐IR UV‐vis spectroscopies, elemental (CHN) analysis, single‐crystal X‐ray diffraction analysis. These exhibited significant IC 50 values in range 9.67 ± 0.17–21.88 0.57 μM. molecular docking results most active complex 2 correlate well vitro observations.

Язык: Английский

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