Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 3, 2024

Abstract Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as crucial contributor development, advancement, resistance This review article explores implications of PI3K in predictive, preventive, personalized medicine for BC. It emphasizes identification predictive biomarkers, such PIK3CA mutations, utility profiling guiding treatment decisions. The also discusses potential targeting preventive strategies customization therapy based on tumor stage, subtypes, genetic alterations. Overcoming inhibitors exploring combination therapies are addressed important considerations. While this field holds promise improving patient outcomes, further research clinical trials needed validate these approaches translate them into practice. Graphical

Language: Английский

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Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial

The Lancet Oncology, Journal Year: 2019, Volume and Issue: 20(12), P. 1750 - 1759

Published: Oct. 24, 2019

Language: Английский

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Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications

The Journal of Pathology, Journal Year: 2018, Volume and Issue: 247(2), P. 214 - 227

Published: Oct. 23, 2018

Abstract Metaplastic breast carcinoma (MBC) is relatively rare but accounts for a significant proportion of global cancer mortality. This group extremely heterogeneous and by definition exhibits metaplastic change to squamous and/or mesenchymal elements, including spindle, squamous, chondroid, osseous, rhabdomyoid features. Clinically, patients are more likely present with large primary tumours (higher stage), distant metastases, overall, have shorter 5‐year survival compared invasive carcinomas no special type. The current World Health Organisation (WHO) diagnostic classification this type based purely on morphology – the biological basis clinical relevance its seven sub‐categories currently unclear. By establishing Asia‐Pacific MBC (AP‐MBC) Consortium, we amassed series MBCs ( n = 347) analysed mutation profile subset, expression 14 biomarkers, clinicopathological correlates, contextualising our findings within WHO guidelines. most indicators poor prognosis were tumour size (T3; p 0.004), loss cytokeratin (lack staining pan‐cytokeratin AE1/3 antibody; 0.007), EGFR overexpression 0.01), ‘mixed’ MBC, presence than three distinct morphological entities 0.007). Conversely, fewer components negativity favourable indicators. Exome sequencing 30 cases confirmed enrichment TP53 PTEN mutations, intriguingly, concurrent mutations , PIK3CA . Mutations in neurofibromatosis‐1 NF1 ) also overrepresented [16.7% ∼5% cancers overall; 0.028; significance 0.006 (OncodriveFM)], consistent published case reports implicating germline risk. Taken together, propose practically minor clinically modification guidelines: all WHO_1 mixed‐type should number morphologies recorded, as mechanism refining prognosis, that important prognostic markers. Copyright © 2018 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.

Language: Английский

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Biomarkers of response and resistance to PI3K inhibitors in estrogen receptor-positive breast cancer patients and combination therapies involving PI3K inhibitors

Annals of Oncology, Journal Year: 2019, Volume and Issue: 30, P. x27 - x42

Published: Aug. 11, 2019

In this review, we discuss biomarkers of response and resistance to PI3K inhibitors (PI3Ki) in estrogen receptor-positive breast cancer, both the early advanced settings. We analyse data regarding PIK3CA mutations, pathway activation, PTEN expression loss, Akt signalling, insulin levels, 18FFDG-PET/CT imaging, FGFR1/2 amplification, KRAS TP53 mutations. Most discussed comprise retrospective exploratory studies, hence many results are not conclusive. Therefore, among all these biomarkers, only mutations have proved a predictive value for treatment with α-selective PI3Ki alpelisib (SOLAR-1 trial) β-sparing taselisib (SANDPIPER setting. Since accuracy current individual is optimal, composite biomarker, including DNA, RNA protein data, more precisely assess PI3K/AKT/mTOR activation status, may arise as promising approach. Finally, describe rational new combination therapies involving anti-HER2 agents, chemotherapy, CDK4/6 inhibitors, mTOR or endocrine treatments ongoing trials field.

Language: Английский

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Epithelial-to-Mesenchymal Transition Signaling Pathways Responsible for Breast Cancer Metastasis

Cellular and Molecular Bioengineering, Journal Year: 2021, Volume and Issue: 15(1), P. 1 - 13

Published: Sept. 2, 2021

Language: Английский

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The Role of Extracellular Matrix Proteins in Breast Cancer

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(5), P. 1250 - 1250

Published: Feb. 25, 2022

The extracellular matrix is a structure composed of many molecules, including fibrillar (types I, II, III, V, XI, XXIV, XXVII) and non-fibrillar collagens (mainly basement membrane collagens: types IV, VIII, X), non-collagenous glycoproteins (elastin, laminin, fibronectin, thrombospondin, tenascin, osteopontin, osteonectin, entactin, periostin) embedded in gel negatively charged water-retaining glycosaminoglycans (GAGs) such as non-sulfated hyaluronic acid (HA) sulfated GAGs which are linked to core protein form proteoglycans (PGs). This highly dynamic molecular network provides critical biochemical biomechanical cues that mediate the cell-cell cell-matrix interactions, influence cell growth, migration differentiation serve reservoir cytokines growth factors' action. breakdown normal ECM its replacement with tumor modulate microenvironment (TME) composition an essential part tumorigenesis metastasis, acting key driver for malignant progression. Abnormal also deregulate behavior stromal cells well facilitating tumor-associated angiogenesis inflammation. Thus, modulates each classically defined hallmarks cancer promoting survival invasion cancer. Moreover, various ECM-derived components immune response affecting T cells, macrophages (TAM), dendritic cancer-associated fibroblasts (CAF). review article considers role play breast Determining detailed connections between cellular processes has helped identify novel disease markers therapeutic targets.

Language: Английский

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Potential miRNA Use as a Biomarker: From Breast Cancer Diagnosis to Metastasis

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 525 - 525

Published: Feb. 6, 2023

Breast cancer is the most common in women. Despite advances diagnosis and prognosis, distal metastases occur these patients up to 15% of cases within 3 years diagnosis. The main organs which BC metastasises are bones, lungs, liver, brain. Unfortunately, 90% metastatic will die, making this an incurable disease. Researchers therefore seeking biomarkers for metastasis different organs. Optimally, such should be easy detect using, preferably, non-invasive methods, as using miRNA molecules, small molecules about 22 nt that have their function post-transcriptional regulation genes. Furthermore, due uncomplicated detection reproducibility laboratory, they a tool complementary interest diagnosis, treatment. With mind, review, we focus on describing current studies propose independently potential biomarker prediction brain, lung, bone metastases, well open window opportunity deepen area study eventually use miRNAs clinical practice benefit patients.

Language: Английский

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Next-Generation sequencing transforming clinical practice and precision medicine

Clinica Chimica Acta, Journal Year: 2023, Volume and Issue: 551, P. 117568 - 117568

Published: Oct. 13, 2023

Language: Английский

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Distinct mRNA expression profiles and miRNA regulators of the PI3K/AKT/mTOR pathway in breast cancer: insights into tumor progression and therapeutic targets

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 9, 2025

Breast cancer remains a leading cause of mortality among women, driven by the molecular complexity its various subtypes. This study aimed to investigate differential expression genes and miRNAs involved in PI3K/AKT/mTOR signaling pathway, critical regulator progression. We analyzed tumor tissues from five breast subtypes-luminal A, luminal B HER2-negative, HER2-positive, triple-negative (TNBC)-and compared them with non-cancerous tissues. Microarray qRT-PCR techniques were employed profile mRNAs miRNAs, while bioinformatic tools predicted miRNA-mRNA interactions. Statistical analysis was performed statistical significance threshold (p) < 0.05. identified several upregulated across all subtypes, TNBC HER2-positive cancers showing most significant changes. Key such as COL1A1, COL4A1, PIK3CA, PIK3R1, mTOR found be overexpressed, correlating increased aggressiveness. miRNA revealed that miR-190a-3p, miR-4729, miR-19a-3p potentially regulate these genes, influencing pathway. For instance, reduced miR-190a-3p may contribute overexpression PIK3CA other pathway components, enhancing metastatic potential. Our findings suggest regulators play crucial roles progression, particularly aggressive subtypes like TNBC. The hold potential biomarkers for diagnosis treatment, but further validation functional studies is required. provides foundation targeted therapies at modulating this improve outcomes.

Language: Английский

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Study Relation between Female Workers’ History and Their Knowledge About Breast Cancer, Breast-Self-Examination and Preventive Measures

Published: Feb. 14, 2025

Background: Breast cancer incidence is significantly higher in patients with a family history, attributed to epigenetic modifications and environmental triggers, regardless of age. Aim: study relation between female workers’ history their knowledge about breast cancer, breast-self-examination preventive measures. Subjects Methods: A 323 Beni-Suef University working women was conducted, focusing on various faculties, from December 2023 May 2024. Tools: Tool I: structured interviewing questionnaire sheet II: women’s self-examination Results: 70.0% females do not have problems, 33.0% discharge issues, 48.3% them were unaware how perform 74.9% did practice it. Moreover, 73.1% didn’t 44.9% get information social media. Regarding total level measures (71.80%, 24.2%, 4%) the following levels: poor, average good, respectively. Conclusion: Based findings present study, it can be concluded that no statistically significant having mammogram problems studied workers

Language: Английский

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