Clinical pharmacokinetics of glipizide: a systematic review.

INTRODUCTION: Glipizide is an oral antidiabetic drug widely used to treat non-insulin-dependent type II diabetes mellitus (NIDDM). This systematic review extensively examines all reported pharmacokinetic (PK) parameters of glipizide in healthy and diseased populations. AREAS COVERED: A total of 31 articles were retrieved after screening various databases, i.e. Google Scholar, PubMed, Science Direct, and Cochrane, regarding the PK parameters of glipizide in healthy, diseased, drug-drug, and drug-food interaction studies. The Cmax was 35% higher in healthy Koreans than in Caucasian Americans. In type II diabetes patients, the AUC0-∞ increases ~2-fold after multiple dosage regimen in comparison with a single dose. Furthermore, the Cmax increased in fasting conditions compared to the non-fasting state in diabetic individuals i.e. 1338.28 ± 125.18 ng/mL and 1297.29 ± 47.22 ng/mL, respectively. EXPERT OPINION: The presented data has depicted that glipizide exposure varies between single and multiple dosing and its Cmax also changes between different demographic populations. Since it has a shorter half-life, the development of its new extended-release formulations may assist practitioners in improving adherence among diabetic patients. PROSPERO REGISTRATION NO: CRD42024538428.

Pseudohypoparathyroidism leading to bilateral hip fracture: A case report.

Pseudohypoparathyroidism (PHP) is a group of disorders characterized by end-organ resistance to parathyroid hormone (PTH), resulting in high serum PTH, low calcium, and high phosphate levels. Among its 5 subtypes, PHP type 1a is the most common and leads to hereditary osteodystrophy, marked by short stature, short metacarpals, and electrolyte abnormalities such as hyperphosphatemia and hypocalcemia, which can cause tetany and seizures. Rarely, PHP patients can experience pathological fractures of long bones. This report discusses a 22-year-old female with PHP who presented with myoclonic seizures and bilateral hip fractures. Initial symptoms included fits, flank pain, and later, leg weakness. Diagnosis was based on clinical history, elevated serum PTH, low calcium, high phosphate, bilateral cataracts, hypothyroidism, basal ganglia calcification, and family history. Treatment began with IV calcium, followed by alfacalcidol, oral calcium, and antibiotics, leading to symptom remission. Hip fractures were managed with a POP cast and later closed reduction. The patient was discharged with calcium and 1,25 dihydroxy Vitamin D supplementation and scheduled for regular follow-up.

The direct cost of chronic kidney disease (CKD) reported in Asian countries; a systematic literature review.

BACKGROUND: The direct and indirect costs of chronic kidney disease (CKD) are substantial and increase over time. Concerns regarding our capacity to manage the financial burden that CKD) places on patients, caregivers, and society are raised by its increasing prevalence and progression. Lack of awareness of CKD's economic effects is a major reason that lawmakers and administrators pay little attention to this chronic illness. OBJECTIVE: We aimed to analyze the direct burden of CKD across Asian countries and evaluate the main cost drivers among all mentioned cost centers in previous studies. METHODOLOGY: Related works evaluating the expenditures of CKD from the perspective of the patient were interpreted by a thorough search of PUBMED and GOOGLE SCHOLAR. RESULTS: Country-wise, in Asia, the direct mean average medical costs in RRT patients were reported in 8 studies as $4574, $18668, $2901, $6848, $16669, $3489, $5945, and $6344 in Singapore, Korea, Taiwan, China, Jordan, Vietnam, Lebanon, and India respectively and the direct mean average medical costs in non-RRT patients were reported in six studies as $3412, $2241, $4534, $290 and $1500 in Singapore, Japan, China, Vietnam, and India respectively. CONCLUSION: Hemodialysis is the main cost driver having an average mean cost of $23,358 per patient per year while the average mean cost of disease management is $4977 per patient per year. More research is needed to understand the specific economic challenges disadvantaged populations face, including the impact of income, education, and access to healthcare resources on the financial burden of CKD.

Clinical pharmacokinetics and pharmacodynamics of nicardipine; a systematic review.

INTRODUCTION: Nicardipine is a type of calcium channel blocker that is commonly used in the treatment of angina pectoris, hypertension, and related cardiovascular disorders. This systematic review assesses the reported pharmacokinetic (PK) and associated pharmacodynamic (PD) parameters of nicardipine in humans. AREAS COVERED: An exhaustive literature search using four internet databases was conducted up to 5 October 2023, which yielded 871 papers, of which 32 fulfilled the eligibility requirements by including human PK and related PD data. The area under the plasma concentration vs. time curve from zero to infinity (AUC0-∞) and maximum plasma concentration (Cmax) of nicardipine rise proportionately with increasing dosage. One study revealed that AUC0-∞ of nicardipine was increased by 5-fold in hepatic cirrhosis patients compared to the control subjects. Moreover, related PD data in renal-impaired hypertensive patients revealed that a notable reduction in blood pressure was associated with nicardipine administration. EXPERT OPINION: This review covers comprehensive data on clinical PK, drug-drug interaction studies, effects of dosage form on ADME, and associated PD parameters of nicardipine using all relevant published studies. The present study will also aid in the development and evaluation of PK models for suggesting model-informed dosing regimens. PROSPERO NUMBER: CRD42024533051.

The Economic Burden of Type 2 Diabetes Mellitus in Pakistan: A Cost of Illness Study.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a highly prevalent disease with a chronic nature and poses a significant health burden worldwide, with no exception in Pakistan. Hence, this study aimed to explore the financial burden of T2DM in Pakistan through cost of illness analysis. METHODS: A prevalence-based, cross-sectional study was conducted using a structured data collection tool from the patient's perspective. Through structured interviews by trained data collectors, the data regarding direct medical costs, direct non-medical costs, and indirect costs were collected and further verified through prescriptions and bills. After testing the normality of data, mean and median with interquartile range were used to present cost data, while non-parametric tests, i.e., the Mann-Whitney U test and the Kruskal-Wallis test, were used to assess factors associated with costs, as cost data were not normally distributed. RESULTS: The study included 522 participants, with a majority being female (54%) and aged between 41 and 60 years (64%). The mean annual total cost per patient was USD 235.1 (median = USD 162.8), comprising direct medical costs, 93.2% (mean = USD 219.2; median = USD 150.0), direct non-medical costs, 5.3% (mean = USD 12.4; median = USD 7.1), and indirect costs, 1.5% (mean = USD 3.5; median = USD 1.9). Costs were significantly higher for patients with advanced age, high literacy, higher household incomes, duration of diabetes, more than one complication, and using combination therapy. CONCLUSIONS: The economic burden of T2DM in Pakistan is substantial, with medication costs being the largest component. Effective management strategies and policy interventions are crucial to mitigate this burden and improve the economic and health outcomes for diabetic patients.

A rare adult presentation of chronic recurrent multifocal osteomyelitis (CRMO) in 38-year female with exclusive spinal involvement.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, autoinflammatory bone disorder most often seen in children and adolescents characterized by recurrent episodes of sterile osteolytic osseous lesions. Diagnosing CRMO requires the exclusion of other conditions, which is often challenging due to its varied presentations and progression. However, adult-onset CRMO and exclusive spinal cases are extremely rare events, highlighting the importance of this case. Our case presents a 38-year-old female with chronic back pain for 6 months of postepidural anesthesia during a C-section. The pain was progressive, exacerbated by movement, and partially relieved by painkillers. The patient had tenderness on physical examination in the thoracolumbar region. MRI of the spine showed multiple endplate changes, and extensive laboratory tests and biopsy ruled out infectious cause and malignancy, leading to the diagnosis of CRMO. The connection between pain and epidural anesthesia was only an incidental finding. The patient was treated effectively with steroids and etanercept. CRMO is mainly a childhood disease, with adult cases being very rare. Isolated spinal involvement in CRMO is particularly rare and can make the diagnosis challenging. This case highlights that CRMO should be considered in adults with an atypical isolated spinal lesion. NSAIDs are the main treatment, with corticosteroids and TNF inhibitors used in unresponsive cases. This case underscores the need for heightened awareness of CRMO's potential to present in adults with atypical isolated spinal lesions, which could lead to more timely and accurate diagnoses.

Acute extensive pulmonary embolism after mRNA SARS-CoV-2 immunization.

COVID-19 vaccines, a cornerstone of the fight against the disease have generally proven to be safe with most commonly reported side effects being mild and self-limiting. Uncommon severe adverse effects like thromboembolism have been reported during postmarketing surveillance. Viral-based vector vaccines have been most commonly implicated in these reports. Our report however portrays a case of a 26-year-old female who developed extensive pulmonary embolism following administration of the Pfizer- BNT162b2 mRNA COVID-19 vaccine. The patient did not have any risk factors for thromboembolism. She was admitted, put on enoxaparin, and given Altaplase thrombolytic therapy. Her condition improved and she was discharged on Apixaban. The Thrombophilia screen performed on the 6-month follow-up was negative and following the resolution of thrombosis, Apixaban was stopped. Our case highlights the importance of continued surveillance of uncommon adverse effects and the need for prompt diagnosis and management of such side effects.

Clinical pharmacokinetics of cefpodoxime: a systematic review.

INTRODUCTION: Cefpodoxime, a third-generation cephalosporin, is a broad-spectrum antibiotic widely used to treat acute upper respiratory tract infections (RTI). This systematic review aims to present a comprehensive view of all the available pharmacokinetics (PK) data associated with the pharmacodynamics (PD) parameters of cefpodoxime in humans. AREAS COVERED: The PubMed, Google Scholar, Cochrane Library, and Science Direct, were systematically searched to identify studies on the PK of cefpodoxime. Out of 746 papers, 26 articles meeting the eligibility criteria were included that have reported the PK data. The drug exposure for the patients undergoing hemodialysis was 50% lower than healthy participants. The renal clearance was almost 27% less in pediatric patients than in adults. The plasma concentrations of cefpodoxime exceeded the minimum inhibitory concentration (MIC) for 90% of skin pathogens, including Streptococcus species and Staphylococcus species (i.e.) < 1 µg/mL and 2-4 µg/mL respectively. EXPERT OPINION: The current study includes detailed information on clinical PK of cefpodoxime in healthy, diseased, pediatric populations as well as drug-drug interactions and drug-food interactions. Moreover, this systematic review also explicated PK/PD properties of drug with a specific impact on MIC of drug. The present review will also assist clinicians in the development of PK models for cefpodoxime.

A Comprehensive Physiologically Based Pharmacokinetic Model for Predicting Vildagliptin Pharmacokinetics: Insights into Dosing in Renal Impairment.

Physiologically based pharmacokinetic (PBPK) modeling is of great importance in the field of medicine. This study aims to construct a PBPK model, which can provide reliable drug pharmacokinetic (PK) predictions in both healthy and chronic kidney disease (CKD) subjects. To do so, firstly a review of the literature was thoroughly conducted and the PK information of vildagliptin was collected. PBPK modeling software, PK-Sim®, was then used to build and assess the IV, oral, and drug-specific models. Next, the average fold error, visual predictive checks, and predicted/observed ratios were used for the assessment of the robustness of the model for all the essential PK parameters. This evaluation demonstrated that all PK parameters were within an acceptable limit of error, i.e., 2 fold. Also to display the influence of CKD on the total and unbound AUC (the area under the plasma concentration-time curve) and to make modifications in dose, the analysis results of the model on this aspect were further examined. This PBPK model has successfully depicted the variations of PK of vildagliptin in healthy subjects and patients with CKD, which can be useful for medical practitioners in dosage optimization in renal disease patients.

Navigating Pakistan's immunization landscape: Progress and pitfalls.

Objectives: This study aims to assess the impact of the 2022 floods in Pakistan on the incidence of vaccine-preventable diseases (VPDs) in flood-affected regions, specifically focusing on areas with traditionally low vaccination coverage. Design: Weekly incidence data of VPDs from September to November 2021 and 2022 were collected and analyzed for the provinces of Sindh, Khyber Pakhtunkhwa, and Baluchistan. The study compared year-on-year changes in disease incidence to evaluate the effect of the floods on disease burden. Results: The analysis revealed significant increases in the incidence of various VPDs in the flood-affected regions compared to the previous year. Diseases such as pertussis showed a 171% increase, while mumps exhibited nearly a 1000% increase in reported cases. Other diseases including polio, diphtheria, neonatal tetanus, measles, chickenpox, and rubella also experienced substantial rises in case numbers. Concurrently, cases of lower respiratory tract illnesses and diarrheal diseases in children under five years old surged notably. Conclusions: The findings underscored the failure of relief and healthcare efforts in managing vaccine-preventable diseases in flood-affected areas of Pakistan. The study highlights an urgent need for targeted intervention strategies, including enhanced immunization drives and healthcare infrastructure improvements in vulnerable regions. The post-flood scenario presents a critical opportunity to address existing challenges in vaccination coverage and to mitigate future disease outbreaks through comprehensive public health initiatives.

Rupture of sinus of Valsalva in a young laborer: A rare case report.

Ruptured sinus of Valsalva (RSOV) upon physical exertion is rare but should be considered in differential in young adults. Symptoms of acute heart failure, hemodynamic instability, and continuous heart murmur raises suspicion for RSOV and requires emergent surgical repair of right ventricular outflow tract.

Unveiling an atypical meningioma amidst stroke symptoms: importance of accurate diagnosis and comprehensive follow-up: A case report.

Meningiomas are common brain tumors that are classified as either benign, atypical, or malignant. This case involves a 75-year-old woman with a medical history of ischemic heart disease, hypertension, and diabetes. She was diagnosed with an atypical meningioma while being evaluated for symptoms related to a stroke. Upon her presentation at the hospital, the patient displayed symptoms such as loss of motor function on the right side of her body, weakness, dysphagia, and aphasia, indicating a possible stroke. Imaging tests confirmed both the stroke symptoms and the presence of an atypical meningioma. The primary focus of her treatment was addressing the stroke symptoms. Despite being asymptomatic for the meningioma, the patient opted for conservative treatment and declined invasive procedures. Her decision was respected, and a plan was put in place for regular monitoring and counseling regarding the meningioma. This case emphasizes the significance of tailored treatment decisions in complicated clinical situations involving incidental brain tumors.

Neuroprotective potential of topiramate, pregabalin and lacosamide combination in a rat model of acute SE and intractable epilepsy: Perspectives from electroencephalographic, neurobehavioral and regional degenerative analysis.

The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining. Results revealed that acute electrophysiological (EEG) profiling of the ASD cocktail markedly halted sharp ictogenic spikes as well as altered dynamics of brain wave oscillations thus validating the need for polytherapy vs. monotherapy. In TLE animals, pharmacological intervention for 6 weeks with topiramate 10 mg/kg in combination with PREG and LAC at the dose of 20 mg/kg exhibited marked protection from SRS incidence, improved body weight, offensive aggression, anxiety-like behavior, cognitive impairments, and depressive-like behavior (p < 0.05). Moreover, combination therapy impeded redox impairments as evidenced by decreased MDA and AchE levels and increased activity of antioxidant SOD, GSH enzymes. Furthermore, polytherapy rescued animals from SE-induced neurodegeneration with increased neuronal density in CA1, CA3c, CA3ab, hilus, and granular cell layer (GCL) of the dentate gyrus. In conclusion, early polytherapy with topiramate in combination with pregabalin and lacosamide prompted synergy and prevented epileptogenesis with associated psychological and neuropathologic alterations.

A rare sight: Childhood blepharochalasis presenting as recurrent eyelid swelling: A case report.

INTRODUCTION AND IMPORTANCE: Blepharochalasis is a rare eyelid condition that usually affects the upper eyelids and is characterized by persistent, painless edema. This article emphasizes how difficult it can be to diagnose blepharochalasis and how crucial it is to take it into account when making a differential diagnosis for recurrent eyelid swelling. Additionally, it highlights the necessity of surgical intervention and the limited effectiveness of medicinal therapy. CASE PRESENTATION: This case report features a 12-year-old kid who has experienced recurring swelling of the upper eyelid for the previous six years. This was eventually diagnosed as a rare condition called blepharochalasis, and treated with blepharoplasty. CLINICAL DISCUSSION: When nephrotic syndrome was first suspected, systemic involvement was ruled out by careful investigation. Upon physical examination, there was laxity of the eyelids and bilateral ptosis. Renal and liver function tests, among other laboratory testing, came back within normal ranges. The patient was sent to plastic surgery and had blepharoplasty. CONCLUSION: Blepharochalasis presents with recurrent eyelids swelling and is often misdiagnosed as other pathologies such as nephrotic syndrome. This case highlights the importance of clinical manifestation and management of blepharochalasis.

Neuroprotective Effect of Brivaracetam and Perampanel Combination on Electrographic Seizures and Behavior Anomalies in Pentylenetetrazole-Kindled Mice.

Pentylenetetrazole (PTZ)-induced kindling is a broadly used experimental model to study the anticonvulsive potential of new and existing chemical moieties with the aim of discovering drugs hindering seizure progression and associated neurological comorbidities. In the present study, the impact of brivaracetam (BRV) (10 and 20 mg/kg) as monotherapy as well as in combination with 0.25 mg/kg of perampanel (PRP) was investigated on seizure progression with simultaneous electroencephalographic changes in PTZ kindling mouse model. Subsequently, mice were experimentally analyzed for anxiety, cognition, and depression after which their brains were biochemically evaluated for oxidative stress. The outcomes demonstrated that BRV alone delayed the kindling process, but BRV + PRP combination significantly (p < 0.0001) protected the mice from seizures of higher severity and demonstrated an antikindling effect. The PTZ-kindled mice exhibited anxiety, memory impairment, and depression in behavioral tests, which were remarkably less (p < 0.001) in animals treated with drug combination (in a dose-dependent manner) as these mice explored central, illuminated, and exposed zones of open-field test, light/dark box, and elevated plus maze. Moreover, memory impairment was demonstrated by kindled mice, which was significantly (p < 0.001) protected by BRV + PRP as animal's spontaneous alteration, object discrimination, and step-through latencies were increased in various tests employed for the assessment of cognitive abilities. The brains of PTZ-kindled mice had increased malondialdehyde and reduced antioxidant enzymes while treatment with BRV + PRP combination prevented kindling-induced elevation in oxidative markers. The outcomes of this study demonstrate that combining the PRP at low dose augmented the antiseizure properties of BRV as both drugs when administered simultaneously hindered the process of kindling by reducing PTZ-induced excessive electrical activity and oxidative stress in the brain.

Impact of bevacizumab on clinical outcomes and its comparison with standard chemotherapy in metastatic colorectal cancer patients: a systematic review and meta-analysis.

Background: Advances in targeted therapies have expanded the treatment options for colorectal cancer (CRC), allowing for more tailored and effective approaches to managing the disease. In targeted therapy, Bevacizumab is a commonly prescribed anti-VEGF monoclonal antibody that has a direct anti-vascular impact in cancer patients. Vascular Endothelial Growth Factors (VEGFs), especially VEGF-A, are significant agents in promoting tumour angiogenesis. Objective: To assess the impact of adding Bevacizumab to chemotherapy on progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer. Methodology: Comprehensive searches have been performed on electronic databases such as PubMed, and Google Scholar using the following terms: colorectal cancer, adenocarcinoma, Bevacizumab, chemotherapy, and monoclonal antibody. Results: In the meta-analysis, 16 out of the 24 included studies were analysed. In the final analysis, incorporating Bevacizumab with chеmothеrapy demonstrated favourable outcomes for OS with a hazard ratio (HR = 0.689,95%CI: 0.51-0.83, I² = 39%, p <0.01) and for PFS with a hazard ratio (HR = 0.77 95% CI: 0.60-0.96, I² = 54%, p < 0.01). The subgroup analysis of PFS, categorised by study dеsign (prospеctivе vs rеtrospеctivе), reveals that the Hazard Ratio (HR = 0.82, 95% CI: 0.62-0.97, I² = 21%, p < 0.01) and for OS with a hazard ratio (HR = 0.73, 95% CI: 0.52-0.86, I² = 17%, p < 0.01). Conclusion: Our findings indicate that combining Bevacizumab with chemotherapy enhances clinical outcomes and results in a significant increase in PFS and OS in patients with metastatic colorectal cancer. Positive outcomes are demonstrated by a substantial 23% increase in PFS and 31% increase in OS in patients with metastatic colorectal cancer who undergo Bevacizumab in conjunction with chemotherapy.

Investigating clinical pharmacokinetics of brivaracetam by using a pharmacokinetic modeling approach.

The development of technology and the processing speed of computing machines have facilitated the evaluation of advanced pharmacokinetic (PK) models, making modeling processes simple and faster. The present model aims to analyze the PK of brivaracetam (BRV) in healthy and diseased populations. A comprehensive literature review was conducted to incorporate the BRV plasma concentration data and its input parameters into PK-Sim software, leading to the creation of intravenous (IV) and oral models for both populations. The developed physiologically based pharmacokinetic (PBPK) model of BRV was then assessed using the visual predictive checks, mean observed/predicted ratios (Robs/pre), and average fold error for PK parameters including the maximum systemic concentration (Cmax), the area under the curve at time 0 to t (AUC0-∞), and drug clearance (CL). The PBPK model of BRV demonstrated that mean Robs/pre ratios of the PK parameters remained within the acceptable limits when assessed against a twofold error margin. Furthermore, model predictions were carried out to assess how AUC0-∞ is affected following the administration of BRV in individuals with varying degrees of liver cirrhosis, ranging from different child-pugh (CP) scores like A, B, and C. Moreover, dose adjustments were recommended by considering the variations in Cmax and CL in various kidney disease stages (mild to severe).

Investigation of hybrid ultrasonic machining process of Nomex honeycomb composite using a toothed disc cutter.

Nomex honeycomb composite (NHC) has been increasingly used in the automotive, aerospace and defence applications due to its excellent thermal and mechanical properties. Its complex cellular hexagonal thin-walled configuration along with heterogeneous, soft and brittle nature pose substantial processing defects such as burr formation, tearing of walls, surface roughness, dimensional inaccuracy and low machining quality during conventional machining (CM). These surface defects have a substantial influence on the operating life and functional performance of its sandwiched structural members. Hybrid ultrasonic vibration assisted machining (HUSVAM) technology has been introduced to overcome such limitations. For an in depth research on HUSVAM of NHC using ultrasonic toothed disc cutter (UTDC), three dimensional finite element model was developed and experimental validation was carried out. The numerical simulation and experimental results were found to be in good agreement with one another. The influence of various machining parameters including the ultrasonic tool vibration amplitude (UTVA), feed rate (FR), depth of cut (DoC) and spindle angular speed (SAS) on NHC cutting forces, chip formation and surface quality was investigated using both HUSVAM and CM techniques. Furthermore, stresses, deformation and forces near tool-workpiece interaction along with the surface topography and morphologies were also analysed and compared for various operating conditions. A reduction in the cutting forces was found with the increase of SAS and UTVA (up to 65.47 % and 65.74 %, respectively). Although, the cutting forces were observed to increase by increasing the DoC and FR (up to 159.45 % and 126.33 %, respectively). DoC has a greater impact on the cutting forces among all machining parameters according to 4 levels, 4 factors (L16) orthogonal experiments based on Taguchi method. The results show that the chip formation and machining quality of NHC core can be improved with HUSVAM technique using UTDC. HUSVAM also reduced the cutting forces (up to 73 %) compared to CM. The ultrasonic toothed disc cutter generated large number of burr with very short length, no tearing defects and no uncut fibers as observed from scanning electron microscopy of NHC hexagonal cell structure, walls and triple points. A burr formation of less than 10 % was realized during HUSVAM of NHC cores for Fx≤3N, while it was found up to 20 % if Fx>3N, compared to at least 40 % during CM. The finite element model developed can be used to investigate the influence of HUSVAM on modern difficult to machine materials for enhanced surface quality.

Recent developments in targeting breast cancer stem cells (BCSCs): a descriptive review of therapeutic strategies and emerging therapies.

Despite recent advancements in the diagnosis and treatment of breast cancer (BC), patient outcomes in terms of survival, recurrence, and disease progression remain suboptimal. A significant factor contributing to these challenges is the cellular heterogeneity within BC, particularly the presence of breast cancer stem cells (BCSCs). These cells are thought to serve as the clonogenic nexus for new tumor growth, owing to their hierarchical organization within the tumor. This descriptive review focuses on the evolving strategies to target BCSCs, which have become a pivotal aspect of therapeutic development. We explore a variety of approaches, including targeting specific tumor surface markers (CD133 and CD44), transporters, heat shock proteins, and critical signaling pathways like Notch, Akt, Hedgehog, KLF4, and Wnt/ß-catenin. Additionally, we discuss the modulation of the tumor microenvironment through the CXCR-12/CXCR4 axis, manipulation of pH levels, and targeting hypoxia-inducible factors, vascular endothelial growth factor, and CXCR1/2 receptors. Further, this review focuses on the roles of microRNA expression, strategies to induce apoptosis and differentiation in BCSCs, dietary interventions, dendritic cell vaccination, oncolytic viruses, nanotechnology, immunotherapy, and gene therapy. We particularly focused on studies reporting identification of BCSCs, their unique properties and the efficacy of various therapeutic modalities in targeting these cells. By dissecting these approaches, we aim to provide insights into the complex landscape of BC treatment and the potential pathways for improving patient outcomes through targeted BCSC therapies.