Biologics, theranostics, and personalized medicine in drug delivery systems

Pharmacological Research, Journal Year: 2024, Volume and Issue: 201, P. 107086 - 107086

Published: Jan. 29, 2024

The progress in human disease treatment can be greatly advanced through the implementation of nanomedicine. This approach involves targeted and cell-specific therapy, controlled drug release, personalized dosage forms, wearable delivery, companion diagnostics. By integrating cutting-edge technologies with delivery systems, greater precision achieved at tissue cellular levels use stimuli-responsive nanoparticles, development electrochemical sensor systems. targeting – by virtue nanotechnology allows for therapy to directed specifically affected tissues while reducing side effects on healthy tissues. As such, nanomedicine has potential transform conditions such as cancer, genetic diseases, chronic illnesses facilitating precise delivery. Additionally, forms devices offer ability tailor unique needs each patient, thereby increasing therapeutic effectiveness compliance. Companion diagnostics further enable efficient monitoring response, enabling customized adjustments plan. question whether all approaches outlined here are viable alternatives current treatments is also discussed. In general, application field biomedicine may provide a strong alternative existing several reasons. this review, we aim present evidence that, although early stages, fully merging technology innovative shows promise successful across various areas, including cancer or diseases.

Language: Английский

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Chemical Scaffolds for the Clinical Development of Mutant-Selective and Reversible Fourth-Generation EGFR-TKIs in NSCLC

ACS Chemical Biology, Journal Year: 2024, Volume and Issue: 19(4), P. 839 - 854

Published: March 29, 2024

In nonsmall cell lung cancer (NSCLC), as well in other tumors, the targeted therapy is mainly represented by tyrosine kinase inhibitors (TKIs), small molecules able to target oncogenic driver alterations affecting gene encoding epidermal growth factor receptor (EGFR). Up now, several different TKIs have been developed. However, cells showed an incredible adaptive tumor response inhibition of sequentially mutated EGFR (EGFRM+), triggering need explore novel pharmacochemical strategies. This Review summarizes recent efforts development new reversible next-generation fight resistance against T790M and C797S mutations. Specifically, after giving overview role EGFR's signaling pathways progression, we are going discuss most relevant approved drugs drug candidates terms chemical structure, binding modalities, their potency selectivity over wild-type form. could provide important guidelines rationale for discovery iterative drugs.

Language: Английский

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Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor models

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 10, 2025

Introduction TAVO412, a multi-specific antibody targeting epidermal growth factor receptor (EGFR), mesenchymal epithelial transition (c-Met), and vascular endothelial A (VEGF-A), is undergoing clinical development for the treatment of solid tumors. TAVO412 has multiple mechanisms action tumor inhibition that include shutting down EGFR, c-Met, VEGF signaling pathways, having enhanced Fc effector functions, addressing drug resistance can be mediated by crosstalk amongst these three targets, as well inhibiting angiogenesis. demonstrated strong in vivo 23 cell-line derived xenograft (CDX) models representing diverse cancer types, 9 patient-derived (PDX) lung models. Methods Using preclinical CDX data, we established transcriptomic biomarkers based on gene expression profiles were correlated with anti-tumor response or distinguished between responders non-responders. Together specific driver mutation associated efficacy targets set 21-gene biomarker was identified to predict efficacy. predictor formulated Linear Prediction Score (LPS) estimate probability patients model treatment. Results This 78% accuracy training The further validated PDX data resulted comparable accuracy. Conclusions In implementing precision medicine leveraging predictive empowered next-generation sequencing could optimize selection may benefit most from

Language: Английский

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Design, Synthesis, and Mechanistic Anticancer Evaluation of New Pyrimidine-Tethered Compounds

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 270 - 270

Published: Feb. 19, 2025

Background: Despite recent breakthroughs in cancer treatment, non-small cell lung (NSCLC) and breast remain major causes of death from all malignancies. The epidermal growth factor receptor (EGFR) is an important mediator the pathways involved proliferation, apoptosis, angiogenesis. Thus, its overexpression triggers several types cancer, including NSCLC cancer. Methods: In current study, we synthesized new pyrimidine-tethered compounds (chalcone derivative (B-4), pyrazoline-carbothioamide (B-9), pyrazoline-thiazole hybrids (BH1-7)). These were then tested for cytotoxicity against A549 MCF-7 cells. Results: Of these, B-4 displayed significant both cells (IC50 = 6.70 ± 1.02 µM MCF-7; IC50 20.49 2.7 A549) compared to standard agent lapatinib 9.71 1.12 18.21 3.25 A549). anticancer potential between Jurkat leukemic T peripheral blood mononuclear (PBMCs) (healthy) was found be selective. Mechanistically, 11.9% 10.2% treated with B-4, respectively, underwent apoptosis produced 46% EGFR inhibition at a concentration 10 μM. B-4/EGFR complex obtained after induced fit docking subjected 300 ns molecular dynamics simulation, which confirmed stability mimicked biological environment. On other hand, shown have drug-like properties by silico pharmacokinetic estimation. Conclusions: inhibitor inducer future studies.

Language: Английский

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Extracellular Vesicles in Lung Cancer: Implementation in Diagnosis and Therapeutic Perspectives

Cancers, Journal Year: 2024, Volume and Issue: 16(11), P. 1967 - 1967

Published: May 22, 2024

Lung cancer represents the leading cause of cancer-related mortality worldwide, with around 1.8 million deaths in 2020. For this reason, there is an enormous interest finding early diagnostic tools and novel therapeutic approaches, one which extracellular vesicles (EVs). EVs are nanoscale membranous particles that can carry proteins, lipids, nucleic acids (DNA RNA), mediating various biological processes, especially cell–cell communication. As such, they represent interesting biomarker for analysis be performed easily by liquid biopsy. Moreover, their growing dataset shows promising results as drug delivery cargo. The aim our work to summarize recent advances possible implications diagnosis innovative therapies lung cancer.

Language: Английский

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Role of Folate Receptor and CD44 in Targeting of Docetaxel and Paclitaxel Fabricated Conjugates for Efficient Cancer Therapy

Journal of Medicine Surgery and Public Health, Journal Year: 2024, Volume and Issue: unknown, P. 100163 - 100163

Published: Dec. 1, 2024

Language: Английский

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Transformation of lung adenocarcinoma to small cell lung cancer following osimertinib treatment: a case report and literature review

Anti-Cancer Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) effectively treat EGFR-mutant lung adenocarcinoma, demonstrating initial efficacy but eventually leading to acquired resistance. Small cell transformation is a rare resistance mechanism EGFR-TKIs in which can complicate clinical diagnosis and treatment. We present patient with adenocarcinoma who underwent prior pneumonectomy adjuvant chemotherapy was treated osimertinib after the recurrence of cancer. occurred approximately 20 months starting After this transformation, radiotherapy cisplatin–etoposide chemotherapy, stabilized disease. Following confirmation small cancer (SCLC) via thyroid puncture, treatments irinotecan, irinotecan plus atezolizumab, radiotherapy, adrenal head were sequentially administered, yet disease continued progress. The succumbed May 2023 because progression organ failure, an overall survival 52.7 months, including 16 post transformation. This case highlights possibility causing transform into SCLC underscores rebiopsies’ importance identifying mechanisms EGFR-TKIs. Increased levels neuron-specific enolase pro-gastrin releasing peptide signal early SCLC.

Language: Английский

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Targeted cancer treatment using a novel EGFR-specific Fc-fusion peptide based on GE11 peptide

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 11, 2025

Fc-fusion peptides, also known as peptibodies, are a promising new category of targeted therapeutics that offer alternatives to monoclonal antibodies (mAbs) for cancer treatment. This study focuses on an peptide consisting the Fc region IgG1 and epidermal growth factor receptor (EGFR)-targeting peptide, GE11, which was identified using phage display method demonstrated high affinity receptor. The fusion (FcIgG-GE11) successfully expressed in Escherichia coli purified ion-exchange chromatography. Flow cytometry confirmed its specific binding EGFR. Like Cetuximab, FcIgG-GE11 peptibody exhibited effective, dose- time-dependent inhibition EGFR-overexpressing cell lines. Additionally, results showed induced death or cycle arrest certain lines, with varying responses depending type. In-Cell ELISA when comparing effects Cetuximab Tyr 1173 phosphorylation were similar. In addition, relative potency compared assessed MTT by Slope Ratio Analysis. These findings suggest can provide efficient tool both targeting treating cells.

Language: Английский

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Establishment and validation of a survival prediction model for stage IV non-small cell lung cancer: a real-world study

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 6, 2025

The aim of this study is to develop and validate a predictive model for predicting survival in individual advanced non-small cell lung cancer patients by integrating basic patient information clinical data. A total 462 with collected from Shanxi Cancer Hospital were randomly assigned (in 7:3 ratio) training cohort an internal validation cohort. Independent factors affecting patients' 3-year screened models created using single-factor followed multifactor Cox regression analysis. Evaluate the performance consistency index (C-index), calibration curves, receiver operating characteristic curves (ROC) decision curve analysis (DCA). who received chemotherapy alone those combined immunotherapy statistically paired propensity score matching between two groups, subgroup analyses performed among variables. better prognostic was nomogram chart visualizing drawn. Based on median risk cohort, all individuals categorized into high- low-risk high-risk group having worse OS both cohorts (P<0.05). results showed that versus NSCLC affected OS. developed predict cancer. demonstrated superior alone.

Language: Английский

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Current diagnostic and therapeutical approaches to bone metastases in patients with non-small cell lung cancer: A cross-sectional study

Lung Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 108531 - 108531

Published: April 1, 2025

The current study aims to investigate the practice of bone metastasis management in patients with non-small cell lung cancer. An online questionnaire was administered 92 oncologists. A survey developed and revised by dedicated experts composed five sections: i) general work characteristics, ii) diagnostic issues, bone-targeted agents iii) radiotherapy iv) supportive care issues. Descriptive statistics applied. 18F-FDG PET is preferred evaluation for skeletal assessment both (62 %) without (54 lesions at CT scan; MRI (63 (61 are most chosen radiographic assessments when a oligoprogression suspected. number metastatic main factor considered deciding whether start (57 %). In choosing between agents, renal toxicity Over half participants did not stop systemic treatment during stereotactic (68 re-irradiation on progressive metastases least 6 months after prior (55 Overall, 64 % 41 assessed patients' body weight physical activity, respectively. Oral nutritional supplements or specific diet were recommended 34 46 clinicians; 40 them also advised their increase activity levels, while 54 worried that exercise might risk skeletal-related adverse events. Lung-cancer clinicians pay great attention metastases-related diagnostic, whereas integration approaches seem less standardized.

Language: Английский

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