Trials and Tribulations of MicroRNA Therapeutics

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1469 - 1469

Published: Jan. 25, 2024

The discovery of the link between microRNAs (miRNAs) and a myriad human diseases, particularly various cancer types, has generated significant interest in exploring their potential as novel class drugs. This led to substantial investments interdisciplinary research fields such biology, chemistry, medical science for development miRNA-based therapies. Furthermore, recent global success SARS-CoV-2 mRNA vaccines against COVID-19 pandemic further revitalized RNA-based immunotherapies, including approaches treatment. Consequently, RNA therapeutics have emerged highly adaptable modular options therapy. Moreover, advancements chemistry delivery methods been pivotal shaping landscape immunotherapy, approaches. biotechnology pharmaceutical industry witnessed resurgence incorporating immunotherapies miRNA into programs. Despite progress preclinical research, field remains its early stages, with only few progressing clinical development, none reaching phase III trials or being approved by US Food Drug Administration (FDA), several facing termination due toxicity issues. These setbacks highlight existing challenges that must be addressed broad application therapeutics. Key include establishing sensitivity, specificity, selectivity towards intended targets, mitigating immunogenic reactions off-target effects, developing enhanced targeted delivery, determining optimal dosing therapeutic efficacy while minimizing side effects. Additionally, limited understanding precise functions miRNAs limits utilization. viable treatment, they technically economically feasible widespread adoption As result, thorough risk evaluation is crucial minimize prevent overdosing, address other Nevertheless, diseases evident, future investigations are essential determine applicability settings.

Language: Английский

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Liquid biopsy techniques and pancreatic cancer: diagnosis, monitoring, and evaluation

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

Published: Oct. 6, 2023

Abstract Pancreatic cancer (PC) is one of the most common malignancies. Surgical resection a potential curative approach for PC, but patients are unsuitable operations when at time diagnosis. Even with surgery, some may still experience tumour metastasis during operation or shortly after as precise prognosis evaluation not always possible. If miss opportunity surgery and resort to chemotherapy, they face challenging issue chemotherapy resistance. In recent years, liquid biopsy has shown promising prospects in disease diagnosis, treatment monitoring, assessment. As noninvasive detection method, offers advantages over traditional diagnostic procedures, such tissue biopsy, terms both cost-effectiveness convenience. The information provided by helps clinical practitioners understand molecular mechanisms underlying occurrence development, enabling formulation more personalized decisions each patient. This review introduces biomarkers methods including circulating cells (CTCs), DNA (ctDNA), noncoding RNAs (ncRNAs), extracellular vesicles (EVs) exosomes. Additionally, we summarize applications early response, resistance assessment, prognostic PC.

Language: Английский

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Beyond blood: Advancing the frontiers of liquid biopsy in oncology and personalized medicine

Cancer Science, Journal Year: 2024, Volume and Issue: 115(4), P. 1060 - 1072

Published: Feb. 3, 2024

Abstract Liquid biopsy is emerging as a pivotal tool in precision oncology, offering noninvasive and comprehensive approach to cancer diagnostics management. By harnessing biofluids such blood, urine, saliva, cerebrospinal fluid, pleural effusions, this technique profiles key biomarkers including circulating tumor DNA, cells, microRNAs, extracellular vesicles. This review discusses the extended scope of liquid biopsy, highlighting its indispensable role enhancing patient outcomes through early detection, continuous monitoring, tailored therapy. While advantages are notable, we also address challenges, emphasizing necessity for precision, cost‐effectiveness, standardized methodologies broader application. The future trajectory set expand reach personalized medicine, fueled by technological advancements collaborative research.

Language: Английский

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Circulating microRNAs as Potential Biomarkers in Pancreatic Cancer—Advances and Challenges

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13340 - 13340

Published: Aug. 28, 2023

There is an urgent unmet need for robust and reliable biomarkers early diagnosis, prognosis, prediction of response to specific treatments many aggressive deadly cancers, such as pancreatic cancer, liquid biopsy-based miRNA profiling has the potential this. MiRNAs are a subset non-coding RNAs that regulate expression multitude genes post-transcriptionally thus diagnostic, prognostic, predictive have also emerged therapeutics. Because miRNAs involved in post-transcriptional regulation their target mRNAs via repressing gene expression, defects biogenesis pathway perturb oncogenic or tumor-suppressive pathogenesis various cancers. As such, numerous been identified be downregulated upregulated functioning either oncomes oncosuppressor miRs. Moreover, dysregulation pathways can change function cancer. Profiling dysregulated cancer shown correlate with disease indicate optimal treatment options predict therapy. Specific signatures track stages hold markers, well therapeutics mimics inhibitors (antagomirs). Furthermore, they along downstream used therapeutic targets. However, limited understanding validation roles miRNAs, lack tissue specificity, methodological, technical, analytical reproducibility, harmonization isolation quantification methods, use standard operating procedures, availability automated standardized assays improve reproducibility between independent studies limit bench-to-bedside translation clinical applications. Here I review recent findings on markers.

Language: Английский

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Circulating Liquid Biopsy Biomarkers in Glioblastoma: Advances and Challenges

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7974 - 7974

Published: July 21, 2024

Gliomas, particularly glioblastoma (GBM), represent the most prevalent and aggressive tumors of central nervous system (CNS). Despite recent treatment advancements, patient survival rates remain low. The diagnosis GBM traditionally relies on neuroimaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scans postoperative confirmation via histopathological molecular analysis. Imaging techniques struggle to differentiate between tumor progression treatment-related changes, leading potential misinterpretation delays. Similarly, tissue biopsies, while informative, are invasive not suitable for monitoring ongoing treatments. These challenges have led emergence liquid biopsy, through blood samples, a promising alternative monitoring. Presently, cerebrospinal fluid (CSF) sampling offers minimally means obtaining tumor-related information guide therapy. idea that any biofluid tests can be used screen many cancer types has huge potential. Tumors release various components into bloodstream other biofluids, including cell-free nucleic acids microRNAs (miRNAs), circulating DNA (ctDNA), cells (CTCs), proteins, extracellular vesicles (EVs) exosomes, metabolites, factors. factors been shown cross blood-brain barrier (BBB), presenting an opportunity well real-time assessment distinct genetic, epigenetic, transcriptomic, proteomic, metabolomic changes associated with brain tumors. their potential, clinical utility biopsy-based biomarkers is somewhat constrained by limitations absence standardized methodologies CSF collection, analyte extraction, analysis methods, small cohort sizes. Additionally, biopsies offer more precise insights morphology microenvironment. Therefore, objective biopsy should complement enhance diagnostic accuracy patients providing additional alongside traditional biopsies. Moreover, utilizing combination diverse biomarker may effectiveness compared solely relying one category, potentially improving sensitivity specificity addressing some existing GBM. This review presents overview latest research found in discusses diagnostic, predictive, prognostic indicators, future perspectives.

Language: Английский

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Genetic Signature of Human Pancreatic Cancer and Personalized Targeting

Cells, Journal Year: 2024, Volume and Issue: 13(7), P. 602 - 602

Published: March 29, 2024

Pancreatic cancer is a highly lethal disease with 5-year survival rate of around 11–12%. Surgery, being the treatment choice, only possible in 20% symptomatic patients. The main reason that when it becomes symptomatic, IT IS tumor usually locally advanced and/or has metastasized to distant organs; thus, early diagnosis infrequent. lack specific symptoms an important cause late diagnosis. Unfortunately, diagnostic markers become positive at stage, and there early-stage markers. Surgical non-surgical cases are treated neoadjuvant adjuvant chemotherapy, results poor. However, personalized targeted therapy directed against drivers may improve this situation. Until recently, many pancreatic driver genes/proteins were considered untargetable. Chemical physical characteristics mutated KRAS formidable challenge overcome. This situation slowly changing. For first time, candidate drugs can target gene cancer: KRAS. Indeed, inhibition been clinically achieved lung and, pre-clinical level, as well. will probably change very poor outlook for disease. paper reviews genetic sporadic hereditary predisposition possibilities according signature.

Language: Английский

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Therapeutic Approaches in Pancreatic Cancer: Recent Updates

Biomedicines, Journal Year: 2023, Volume and Issue: 11(6), P. 1611 - 1611

Published: June 1, 2023

Cancer is a significant challenge for effective treatment due to its complex mechanism, different progressing stages, and lack of adequate procedures screening identification. Pancreatic cancer typically identified in advanced progression phase with low survival ~5 years. Among cancers, pancreatic also considered high mortality-causing casualty over other accidental or disease-based mortality, it ranked seventh among all mortality-associated cancers globally. Henceforth, developing diagnostic early detection, understanding cancer-linked mechanisms, various therapeutic strategies are crucial. This review describes the recent development progression, approaches, including molecular techniques biomedicines effectively treating cancer.

Language: Английский

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Advancements and Applications of Liquid Biopsies in Oncology: A Narrative Review

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: July 31, 2023

According to the World Health Organization (WHO), nearly 10 million people died from cancer worldwide in 2020, making it leading cause of mortality. Liquid biopsies, which provide non-invasive and real-time monitoring tumor dynamics, have evolved into innovative diagnostic techniques field oncology. biopsies offer important insights heterogeneity, treatment response, minimum residual disease identification, personalized through analysis circulating DNA (ctDNA), cells (CTCs), extracellular vesicles, microRNAs. They several advantages over traditional tissue such as being less invasive, more convenient, representative heterogeneity informative for guiding decisions. are utilized increasingly clinical oncology, particularly patients with metastatic who require ongoing modification. In this narrative review article, we latest developments liquid biopsy technologies, their applications limitations, potential transform diagnosis, prognosis, management patients.

Language: Английский

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The expansion of liquid biopsies to vascular care: an overview of existing principles, techniques and potential applications to vascular malformation diagnostics

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 18, 2024

Vascular malformations are congenital lesions that occur due to mutations in major cellular signalling pathways which govern angiogenesis, cell proliferation, motility, and death. These have been widely studied oncology substrates for various small molecule inhibitors. Given their common molecular biology, there is now a potential repurpose these cancer drugs vascular malformation care; however, diagnosis required order tailour specific the individual patient’s mutational profile. Liquid biopsies (LBs), emerging as transformative tool field of oncology, hold significant promise this feat. This paper explores principles technologies underlying LBs evaluates revolutionize management malformations. The review begins by delineating fundamental LBs, focusing on detection analysis circulating biomarkers such cell-free DNA, tumor cells, extracellular vesicles. Subsequently, an in-depth technological advancements driving LB platforms presented. Lastly, highlights current state research applying malformations, uses aforementioned techniques conceptualize liquid biopsy framework unique clinical care.

Language: Английский

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The Current Role of Circulating Tumor DNA in the Management of Pancreatic Cancer

Journal of Gastrointestinal Cancer, Journal Year: 2025, Volume and Issue: 56(1)

Published: Jan. 14, 2025

Language: Английский

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