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Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Clinical Pharmaceutics".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 39094

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Special Issue Editors

Dr. Cristina Manuela Dragoi

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Department of Biochemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956 Bucharest, Romania
Interests: nutrition; drug design; drugs mechanisms of action; nutrients-drug interactions; precision medicine; biological drugs; chronobiology; pharmacogenomics
Special Issues, Collections and Topics in MDPI journals

Dr. Alina Crenguța Nicolae

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Guest Editor

Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, 020956 Bucharest, Romania
Interests: biochemistry; nutrition; drug resistance; P-glycoprotein; neuroscience; clinical research; personalized medicine
Special Issues, Collections and Topics in MDPI journals

Dr. Ion-Bogdan Dumitrescu

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Guest Editor

Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, 020956 Bucharest, Romania
Interests: pharmaceutical 3D printing; computer-aided design; clinical pharmacy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Modern medicine is going through an extremely important moment in its evolution in relation to the disease–drug–patient axis, gradually progressing from pure drug development, which initiates from the need to prevent or treat certain diseases, to the expansion of coherent therapeutic strategies which are personalized for each individual, in recognition of the fact that each patient is a distinct physio-pathological case. Remarkable advances in recent decades in the prevention strategies, diagnostic procedures and available treatments have paved the way to major improvements in patient care. Personalized medicine is approachable if comprehensive details are known about the pathogenesis; the therapeutic agents developed for the management of the pathology in question; the biochemical mechanisms of action of the drugs; the interactions of the drugs with each other and with other endogenous or exogenous factors; and the genetic and epigenetic background of the patient, their chronobiological, nutritional and socio-demographic characteristics.

In this framework, the aim of this Special Issue on “Emerging strategies in drug development and clinical care in the era of personalized and precision medicine” is to unify the most relevant papers addressing the state-of-the-art knowledge and future directions in drug development, therapeutic strategies, and innovative drug formulations, with a focus on biochemical mechanisms of action and drug design, as well as the relevant preclinical and clinical testing of efficacy, pharmacokinetics and toxicity in the era of precision and personalized medicine.

We welcome articles dealing with all aspects of pharmaceutical and medical care, from basic to clinical research, and invite scientists and drug specialists to publish their original research works, review articles, and communications on this wide health domain.

Dr. Cristina Manuela Drăgoi
Dr. Alina Crenguța Nicolae
Dr. Ion-Bogdan Dumitrescu
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

drug development
therapeutic strategies
preclinical and clinical drug research
drug design
drug–drug interactions
clinical care
toxicological studies
disease risk, disease prognosis and response to therapy
biomarkers identification and application
biochemistry of drug uptake, action, and metabolism
drug target discovery
individualized therapy
pharmacogenomics
novel therapeutics
non-drug-related health interferences
nutritional interventions
chronobiology
medicinal chemistry
phytochemicals
biologics
personalized medicine
precision medicine

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Published Papers (14 papers)

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Editorial

Jump to: Research, Review

7 pages, 218 KiB

Open AccessEditorial

Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine

by Cristina Manuela Drăgoi, Alina Crenguța Nicolae and Ion-Bogdan Dumitrescu

Pharmaceutics 2024, 16(8), 1107; https://doi.org/10.3390/pharmaceutics16081107 - 22 Aug 2024

Viewed by 784

Abstract

In the ever-changing landscape of modern medicine, we face an important moment where the interplay of disease, drugs, and patients defines a new paradigm [...] Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

Research

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12 pages, 250 KiB

Open AccessArticle

Point Prevalence Survey of Acute Hospital Patients with Difficulty Swallowing Solid Oral Dose Forms

by Anne Harnett, Stephen Byrne, Jennifer O’Connor, Eimear Burke, Laura South, Declan Lyons and Laura J. Sahm

Pharmaceutics 2024, 16(5), 584; https://doi.org/10.3390/pharmaceutics16050584 - 25 Apr 2024

Viewed by 1007

Abstract

The safe administration of solid oral dose forms in hospital inpatients with swallowing difficulties is challenging. The aim of this study was to establish the prevalence of difficulties in swallowing solid oral dose forms in acute hospital inpatients. A point prevalence study was completed at three time points. The following data were collected: the prevalence of swallowing difficulties, methods used to modify solid oral dose forms to facilitate administration, the appropriateness of the modification, and patient co-morbidities. The prevalence of acute hospital inpatients with swallowing difficulties was an average of 15.4% with a 95% CI [13.4, 17.6] across the three studies. On average, 9.6% of patients with swallowing difficulties had no enteral feeding tube in situ, with 6.0% of these patients receiving at least one modified medicine. The most common method of solid oral dose form modification was crushing, with an administration error rate of approximately 14.4%. The most common co-morbid condition in these patients was hypertension, with dysphagia appearing on the problem list of two (5.5%) acute hospital inpatients with swallowing difficulties. Inappropriate modifications to solid oral dose forms to facilitate administration can result in patient harm. A proactive approach, such as the use of a screening tool to identify acute hospital inpatients with swallowing difficulties, is required, to mitigate the risk of inappropriate modifications to medicines to overcome swallowing difficulties. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

16 pages, 1346 KiB

Open AccessArticle

Exploring the Impact of Model-Informed Precision Dosing on Procalcitonin Concentrations in Critically Ill Patients: A Secondary Analysis of the DOLPHIN Trial

by Sarah Dräger, Tim M. J. Ewoldt, Alan Abdulla, Wim J. R. Rietdijk, Nelianne Verkaik, Christian Ramakers, Evelien de Jong, Michael Osthoff, Birgit C. P. Koch and Henrik Endeman

Pharmaceutics 2024, 16(2), 270; https://doi.org/10.3390/pharmaceutics16020270 - 14 Feb 2024

Viewed by 1240

Abstract

Model-informed precision dosing (MIPD) might be used to optimize antibiotic treatment. Procalcitonin (PCT) is a biomarker for severity of infection and response to antibiotic treatment. The aim of this study was to assess the impact of MIPD on the course of PCT and to investigate the association of PCT with pharmacodynamic target (PDT) attainment in critically ill patients. This is a secondary analysis of the DOLPHIN trial, a multicentre, open-label, randomised controlled trial. Patients with a PCT value available at day 1 (T1), day 3 (T3), or day 5 (T5) after randomisation were included. The primary outcome was the absolute difference in PCT concentration at T1, T3, and T5 between the MIPD and the standard dosing group. In total, 662 PCT concentrations from 351 critically ill patients were analysed. There was no statistically significant difference in PCT concentration between the trial arms at T1, T3, or T5. The median PCT concentration was highest in patients who exceeded 10× PDT at T1 [13.15 ng/mL (IQR 5.43–22.75)]. In 28-day non-survivors and in patients that exceeded PDT at T1, PCT decreased significantly between T1 and T3, but plateaued between T3 and T5. PCT concentrations were not significantly different between patients receiving antibiotic treatment with or without MIPD guidance. The potential of PCT to guide antibiotic dosing merits further investigation. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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14 pages, 5481 KiB

Open AccessArticle

Exploring Metabolic Pathways of Anamorelin, a Selective Agonist of the Growth Hormone Secretagogue Receptor, via Molecular Networking

by Young Beom Kwak, Jeong In Seo and Hye Hyun Yoo

Pharmaceutics 2023, 15(12), 2700; https://doi.org/10.3390/pharmaceutics15122700 - 29 Nov 2023

Cited by 5 | Viewed by 1827

Abstract

In this study, we delineated the poorly characterized metabolism of anamorelin, a growth hormone secretagogue receptor agonist, in vitro using human liver microsomes (HLM), based on classical molecular networking (MN) and feature-based molecular networking (FBMN) from the Global Natural Products Social Molecular Networking platform. Following the in vitro HLM reaction, the MN analysis showed 11 neighboring nodes whose information propagated from the node corresponding to anamorelin. The FBMN analysis described the separation of six nodes that the MN analysis could not achieve. In addition, the similarity among neighboring nodes could be discerned via their respective metabolic pathways. Collectively, 18 metabolites (M1–M12) were successfully identified, suggesting that the metabolic pathways involved were demethylation, hydroxylation, dealkylation, desaturation, and N-oxidation, whereas 6 metabolites (M13a*-b*, M14a*-b*, and M15a*-b*) remained unidentified. Furthermore, the major metabolites detected in HLM, M1 and M7, were dissimilar from those observed in the CYP3A4 isozyme assay, which is recognized to be markedly inhibited by anamorelin. Specifically, M7, M8, and M9 were identified as the major metabolites in the CYP3A4 isozyme assay. Therefore, a thorough investigation of metabolism is imperative for future in vivo studies. These findings may offer prospective therapeutic opportunities for anamorelin. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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15 pages, 4118 KiB

Open AccessArticle

Selegiline Modulates Lipid Metabolism by Activating AMPK Pathways of Epididymal White Adipose Tissues in HFD-Fed Obese Mice

by Hye-Young Joung, Jung-Mi Oh, Min-Suk Song, Young-Bae Kwon and Sungkun Chun

Pharmaceutics 2023, 15(11), 2539; https://doi.org/10.3390/pharmaceutics15112539 - 27 Oct 2023

Cited by 1 | Viewed by 2092

Abstract

Obesity, as a major cause of many chronic diseases such as diabetes, cardiovascular disease, and cancer, is among the most serious health problems. Increased monoamine oxidase (MAO) activity has been observed in the adipose tissue of obese humans and animals. Although previous studies have already demonstrated the potential of MAO-B inhibitors as a treatment for this condition, the mechanism of their effect has been insufficiently elucidated. In this study, we investigated the anti-obesity effect of selegiline, a selective MAO-B inhibitor, using in vivo animal models. The effect was evaluated through an assessment of body energy homeostasis, glucose tolerance tests, and biochemical analysis. Pharmacological inhibition of MAO-B by selegiline was observed to reduce body weight and fat accumulation, and improved glucose metabolism without a corresponding change in food intake, in HFD-fed obese mice. We also observed that both the expression of adipogenenic markers, including C/EBPα and FABP4, and lipogenic markers such as pACC were significantly reduced in epididymal white adipose tissues (eWATs). Conversely, increased expression of lipolytic markers such as ATGL and pHSL and AMPK phosphorylation were noted. Treating obese mice with selegiline significantly increased expression levels of UCP1 and promoted eWAT browning, indicating increased energy expenditure. These results suggest that selegiline, by inhibiting MAO-B activity, is a potential anti-obesity treatment. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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16 pages, 3154 KiB

Open AccessArticle

Toward Stability Enhancement of NTS₁R-Targeted Radioligands: Structural Interventions on [^99mTc]Tc-DT1

by Panagiotis Kanellopoulos, Berthold A. Nock, Eric P. Krenning and Theodosia Maina

Pharmaceutics 2023, 15(8), 2092; https://doi.org/10.3390/pharmaceutics15082092 - 7 Aug 2023

Cited by 2 | Viewed by 1294

Abstract

The neurotensin subtype 1 receptor (NTS₁R) is overexpressed in a number of human tumors, thereby representing a valid target for cancer theranostics with radiolabeled neurotensin (NT) analogs like [^99mTc]Tc-DT1 (DT1, N₄-Gly⁷-NT(8-13)). Thus far, the fast degradation of intravenously injected NT–radioligands by neprilysin (NEP) and angiotensin-converting enzyme (ACE) has compromised their clinical applicability. Aiming at metabolic stability enhancements, we herein introduce (i) DT7 ([DAsn¹⁴]DT1) and (ii) DT8 ([β-Homoleucine¹³]DT1), modified at the C-terminus, along with (iii) DT9 ([(palmitoyl)Lys⁷]DT1), carrying an albumin-binding domain (ABD) at Lys⁷. The biological profiles of the new [^99mTc]Tc–radioligands were compared with [^99mTc]Tc-DT1, using NTS₁R-expressing AsPC-1 cells and mice models without or during NEP/ACE inhibition. The radioligands showed enhanced in vivo stability vs. [^99mTc]Tc-DT1, with [^99mTc]Tc-DT9 displaying full resistance to both peptidases. Furthermore, [^99mTc]Tc-DT9 achieved the highest cell internalization and tumor uptake even without NEP/ACE-inhibition but with unfavorably high background radioactivity levels. Hence, unlike C-terminal modification, the introduction of a pendant ABD group in the linker turned out to be the most promising strategy toward metabolic stability, cell uptake, and tumor accumulation of [^99mTc]Tc-DT1 mimics. To improve the observed suboptimal pharmacokinetics of [^99mTc]Tc-DT9, the replacement of palmitoyl on Lys⁷ by other ABD groups is currently being pursued. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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16 pages, 6110 KiB

Open AccessArticle

Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy

by Rui Silva, Helena Colom, Joana Bicker, Anabela Almeida, Ana Silva, Francisco Sales, Isabel Santana, Amílcar Falcão and Ana Fortuna

Pharmaceutics 2023, 15(6), 1704; https://doi.org/10.3390/pharmaceutics15061704 - 10 Jun 2023

Cited by 2 | Viewed by 1588

Abstract

Perampanel is a promising antiepileptic drug (AED) for refractory epilepsy treatment due to its innovative mechanism of action. This study aimed to develop a population pharmacokinetic (PopPK) model to be further used in initial dose optimization of perampanel in patients diagnosed with refractory epilepsy. A total of seventy-two plasma concentrations of perampanel obtained from forty-four patients were analyzed through a population pharmacokinetic approach by means of nonlinear mixed effects modeling (NONMEM). A one-compartment model with first-order elimination best described the pharmacokinetic profiles of perampanel. Interpatient variability (IPV) was entered on clearance (CL), while the residual error (RE) was modeled as proportional. The presence of enzyme-inducing AEDs (EIAEDs) and body mass index (BMI) were found as significant covariates for CL and volume of distribution (V), respectively. The mean (relative standard error) estimates for CL and V of the final model were 0.419 L/h (5.56%) and 29.50 (6.41%), respectively. IPV was 30.84% and the proportional RE was 6.44%. Internal validation demonstrated an acceptable predictive performance of the final model. A reliable population pharmacokinetic model was successfully developed, and it is the first enrolling real-life adults diagnosed with refractory epilepsy. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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16 pages, 1857 KiB

Open AccessArticle

Angiotensin II Receptor Blockers Reduce Tau/Aß42 Ratio: A Cerebrospinal Fluid Biomarkers’ Case-Control Study

by Gemma García-Lluch, Carmen Peña-Bautista, Lucrecia Moreno Royo, Miguel Baquero, Antonio José Cañada-Martínez and Consuelo Cháfer-Pericás

Pharmaceutics 2023, 15(3), 924; https://doi.org/10.3390/pharmaceutics15030924 - 12 Mar 2023

Cited by 5 | Viewed by 2209

Abstract

(1) Background: The role of antihypertensives in Alzheimer’s Disease (AD) prevention is controversial. This case-control study aims to assess whether antihypertensive medication has a protective role by studying its association with amyloid and tau abnormal levels. Furthermore, it suggests a holistic view of the involved pathways between renin-angiotensin drugs and the tau/amyloidß42 ratio (tau/Aß42 ratio); (2) Methods: The medical records of the participant patients were reviewed, with a focus on prescribed antihypertensive drugs and clinical variables, such as arterial blood pressure. The Anatomical Therapeutic Chemical classification was used to classify each drug. The patients were divided into two groups: patients with AD diagnosis (cases) and cognitively healthy patients (control); (3) Results: Age and high systolic blood pressure are associated with a higher risk of developing AD. In addition, combinations of angiotensin II receptor blockers are associated with a 30% lower t-tau/Aß42 ratio than plain angiotensin-converting enzyme inhibitor consumption; (4) Conclusions: Angiotensin II receptor blockers may play a potential role in neuroprotection and AD prevention. Likewise, several mechanisms, such as the PI3K/Akt/GSK3ß or the ACE1/AngII/AT1R axis, may link cardiovascular pathologies and AD presence, making its modulation a pivotal point in AD prevention. The present work highlights the central pathways in which antihypertensives may affect the presence of pathological amyloid and tau hyperphosphorylation. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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21 pages, 3336 KiB

Open AccessArticle

Kinin B₁ and B₂ Receptors Contribute to Cisplatin-Induced Painful Peripheral Neuropathy in Male Mice

by Gabriela Becker, Maria Fernanda Pessano Fialho, Indiara Brusco and Sara Marchesan Oliveira

Pharmaceutics 2023, 15(3), 852; https://doi.org/10.3390/pharmaceutics15030852 - 6 Mar 2023

Cited by 4 | Viewed by 2300

Abstract

Cisplatin is the preferential chemotherapeutic drug for highly prevalent solid tumours. However, its clinical efficacy is frequently limited due to neurotoxic effects such as peripheral neuropathy. Chemotherapy-induced peripheral neuropathy is a dose-dependent adverse condition that negatively impacts quality of life, and it may determine dosage limitations or even cancer treatment cessation. Thus, it is urgently necessary to identify pathophysiological mechanisms underlying these painful symptoms. As kinins and their B₁ and B₂ receptors contribute to the development of chronic painful conditions, including those induced by chemotherapy, the contribution of these receptors to cisplatin-induced peripheral neuropathy was evaluated via pharmacological antagonism and genetic manipulation in male Swiss mice. Cisplatin causes painful symptoms and impaired working and spatial memory. Kinin B₁ (DALBK) and B₂ (Icatibant) receptor antagonists attenuated some painful parameters. Local administration of kinin B₁ and B₂ receptor agonists (in sub-nociceptive doses) intensified the cisplatin-induced mechanical nociception attenuated by DALBK and Icatibant, respectively. In addition, antisense oligonucleotides to kinin B₁ and B₂ receptors reduced cisplatin-induced mechanical allodynia. Thus, kinin B₁ and B₂ receptors appear to be potential targets for the treatment of cisplatin-induced painful symptoms and may improve patients’ adherence to treatment and their quality of life. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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9 pages, 2589 KiB

Open AccessArticle

Clinical and Electrophysiological Changes in Pediatric Spinal Muscular Atrophy after 2 Years of Nusinersen Treatment

by Mihaela Axente, Andrada Mirea, Corina Sporea, Liliana Pădure, Cristina Manuela Drăgoi, Alina Crenguța Nicolae and Daniela Adriana Ion

Pharmaceutics 2022, 14(10), 2074; https://doi.org/10.3390/pharmaceutics14102074 - 29 Sep 2022

Cited by 8 | Viewed by 2398

Abstract

In the new therapeutic era, disease-modifying treatment (nusinersen) has changed the natural evolution of spinal muscular atrophy (SMA), creating new phenotypes. The main purpose of the retrospective observational study was to explore changes in clinical evolution and electrophysiological data after 2 years of nusinersen treatment. We assessed distal compound motor action potential (CMAP) on the ulnar nerve and motor abilities in 34 SMA patients, aged between 1 and 16 years old, under nusinersen treatment, using specific motor scales for types 1, 2 and 3. The evaluations were performed at treatment initiation and 26 months later. There were registered increased values for CMAP amplitudes after 2 years of nusinersen, significantly correlated with motor function evolution in SMA type 1 patients (p < 0.005, r = 0.667). In total, 45% of non-sitters became sitters and 25% of sitters became walkers. For SMA types 1 and 2, the age at the treatment initialization is highly significant (p < 0.0001) and correlated with treatment yield. A strong negative correlation (r = −0.633) was observed for SMA type 1 and a very strong negative correlation (r = −0.813) for SMA type 2. In treated SMA cases, the distal amplitude of the CMAP and motor functional scales are important prognostic factors, and early diagnosis and treatment are essential for a better outcome. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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Review

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41 pages, 2720 KiB

Open AccessReview

Advancing Precision Medicine: A Review of Innovative In Silico Approaches for Drug Development, Clinical Pharmacology and Personalized Healthcare

by Lara Marques, Bárbara Costa, Mariana Pereira, Abigail Silva, Joana Santos, Leonor Saldanha, Isabel Silva, Paulo Magalhães, Stephan Schmidt and Nuno Vale

Pharmaceutics 2024, 16(3), 332; https://doi.org/10.3390/pharmaceutics16030332 - 27 Feb 2024

Cited by 25 | Viewed by 11984

Abstract

The landscape of medical treatments is undergoing a transformative shift. Precision medicine has ushered in a revolutionary era in healthcare by individualizing diagnostics and treatments according to each patient’s uniquely evolving health status. This groundbreaking method of tailoring disease prevention and treatment considers individual variations in genes, environments, and lifestyles. The goal of precision medicine is to target the “five rights”: the right patient, the right drug, the right time, the right dose, and the right route. In this pursuit, in silico techniques have emerged as an anchor, driving precision medicine forward and making this a realistic and promising avenue for personalized therapies. With the advancements in high-throughput DNA sequencing technologies, genomic data, including genetic variants and their interactions with each other and the environment, can be incorporated into clinical decision-making. Pharmacometrics, gathering pharmacokinetic (PK) and pharmacodynamic (PD) data, and mathematical models further contribute to drug optimization, drug behavior prediction, and drug–drug interaction identification. Digital health, wearables, and computational tools offer continuous monitoring and real-time data collection, enabling treatment adjustments. Furthermore, the incorporation of extensive datasets in computational tools, such as electronic health records (EHRs) and omics data, is also another pathway to acquire meaningful information in this field. Although they are fairly new, machine learning (ML) algorithms and artificial intelligence (AI) techniques are also resources researchers use to analyze big data and develop predictive models. This review explores the interplay of these multiple in silico approaches in advancing precision medicine and fostering individual healthcare. Despite intrinsic challenges, such as ethical considerations, data protection, and the need for more comprehensive research, this marks a new era of patient-centered healthcare. Innovative in silico techniques hold the potential to reshape the future of medicine for generations to come. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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38 pages, 1294 KiB

Open AccessReview

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

by María Del Mar Sánchez Suárez, Alicia Martín Roldán, Carolina Alarcón-Payer, Miguel Ángel Rodríguez-Gil, Jaime Eduardo Poquet-Jornet, José Manuel Puerta Puerta and Alberto Jiménez Morales

Pharmaceutics 2024, 16(1), 55; https://doi.org/10.3390/pharmaceutics16010055 - 29 Dec 2023

Viewed by 2646

Abstract

Chronic lymphocytic leukemia is a lymphoproliferative disorder marked by the expansion of monoclonal, mature CD5+CD23+ B cells in peripheral blood, secondary lymphoid tissues, and bone marrow. The disease exhibits significant heterogeneity, with numerous somatic genetic alterations identified in the neoplastic clone, notably mutated TP53 and immunoglobulin heavy chain mutational statuses. Recent studies emphasize the pivotal roles of genetics and patient fragility in treatment decisions. This complexity underscores the need for a personalized approach, tailoring interventions to individual genetic profiles for heightened efficacy. The era of personalized treatment in CLL signifies a transformative shift, holding the potential for improved outcomes in the conquest of this intricate hematologic disorder. This review plays a role in elucidating the evolving CLL treatment landscape, encompassing all reported genetic factors. Through a comprehensive historical analysis, it provides insights into the evolution of CLL management. Beyond its retrospective nature, this review could be a valuable resource for clinicians, researchers, and stakeholders, offering a window into the latest advancements. In essence, it serves as a dynamic exploration of our current position and the promising prospects on the horizon. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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17 pages, 1420 KiB

Open AccessReview

DNA and RNA Molecules as a Foundation of Therapy Strategies for Treatment of Cardiovascular Diseases

by Ljiljana Rakicevic

Pharmaceutics 2023, 15(8), 2141; https://doi.org/10.3390/pharmaceutics15082141 - 15 Aug 2023

Viewed by 1997

Abstract

There has always been a tendency of medicine to take an individualised approach to treating patients, but the most significant advances were achieved through the methods of molecular biology, where the nucleic acids are in the limelight. Decades of research of molecular biology resulted in setting medicine on a completely new platform. The most significant current research is related to the possibilities that DNA and RNA analyses can offer in terms of more precise diagnostics and more subtle stratification of patients in order to identify patients for specific therapy treatments. Additionally, principles of structure and functioning of nucleic acids have become a motive for creating entirely new therapy strategies and an innovative generation of drugs. All this also applies to cardiovascular diseases (CVDs) which are the leading cause of mortality in developed countries. This review considers the most up-to-date achievements related to the use of translatory potential of DNA and RNA in treatment of cardiovascular diseases, and considers the challenges and prospects in this field. The foundations which allow the use of translatory potential are also presented. The first part of this review focuses on the potential of the DNA variants which impact conventional therapies and on the DNA variants which are starting points for designing new pharmacotherapeutics. The second part of this review considers the translatory potential of non-coding RNA molecules which can be used to formulate new generations of therapeutics for CVDs. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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15 pages, 1677 KiB

Open AccessReview

Applications of Exosomes in Diagnosing Muscle Invasive Bladder Cancer

by Jillian Marie Walker, Padraic O’Malley and Mei He

Pharmaceutics 2022, 14(10), 2027; https://doi.org/10.3390/pharmaceutics14102027 - 23 Sep 2022

Cited by 3 | Viewed by 3129

Abstract

Muscle Invasive Bladder Cancer (MIBC) is a subset of bladder cancer with a significant risk for metastases and death. It accounts for nearly 25% of bladder cancer diagnoses. A diagnostic work-up for MIBC is inclusive of urologic evaluation, radiographic imaging with a CT scan, urinalysis, and cystoscopy. These evaluations, especially cystoscopy, are invasive and carry the risk of secondary health concerns. Non-invasive diagnostics such as urine cytology are an attractive alternative currently being investigated to mitigate the requirement for cystoscopy. A pitfall in urine cytology is the lack of available options with high reliability, specificity, and sensitivity to malignant bladder cells. Exosomes are a novel biomarker source which could resolve some of the concerns with urine cytology, due to the high specificity as the surrogates of tumor cells. This review serves to define muscle invasive bladder cancer, current urine cytology methods, the role of exosomes in MIBC, and exosomes application as a diagnostic tool in MIBC. Urinary exosomes as the specific populations of extracellular vesicles could provide additional biomarkers with specificity and sensitivity to bladder malignancies, which are a consistent source of cellular information to direct clinicians for developing treatment strategies. Given its strong presence and differentiation ability between normal and cancerous cells, exosome-based urine cytology is highly promising in providing a perspective of a patient’s bladder cancer. Full article

(This article belongs to the Special Issue Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine)

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