Breast cancer: pathogenesis and treatments

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 18, 2025

Abstract Breast cancer, characterized by unique epidemiological patterns and significant heterogeneity, remains one of the leading causes malignancy-related deaths in women. The increasingly nuanced molecular subtypes breast cancer have enhanced comprehension precision treatment this disease. mechanisms tumorigenesis progression been central to scientific research, with investigations spanning various perspectives such as tumor stemness, intra-tumoral microbiota, circadian rhythms. Technological advancements, particularly those integrated artificial intelligence, significantly improved accuracy detection diagnosis. emergence novel therapeutic concepts drugs represents a paradigm shift towards personalized medicine. Evidence suggests that optimal diagnosis models tailored individual patient risk expected are crucial, supporting era oncology for cancer. Despite rapid advancements increasing emphasis on clinical comprehensive update summary panoramic knowledge related disease needed. In review, we provide thorough overview global status including its epidemiology, factors, pathophysiology, subtyping. Additionally, elaborate latest research into contributing progression, emerging strategies, long-term management. This review offers valuable insights Cancer Research, thereby facilitating future progress both basic application.

Язык: Английский

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Resistance to Targeted Inhibitors of the PI3K/AKT/mTOR Pathway in Advanced Oestrogen-Receptor-Positive Breast Cancer

Cancers, Год журнала: 2024, Номер 16(12), С. 2259 - 2259

Опубликована: Июнь 18, 2024

The PI3K/AKT/mTOR signalling pathway is one of the most frequently activated pathways in breast cancer and also plays a central role regulation several physiologic functions. There are major efforts ongoing to exploit precision medicine by developing inhibitors that target three kinases (PI3K, AKT, mTOR). Although multiple compounds have been developed, at present, there just approved this patients with advanced ER-positive, HER2-negative cancer: everolimus (mTOR inhibitor), alpelisib (PIK3CA capivasertib (AKT inhibitor). Like targeted drugs, resistance poses problem clinical setting factor has limited overall efficacy these agents. Drug can be categorised into intrinsic or acquired depending on timeframe it developed within. Whereas exists prior specific treatment, induced therapy. majority will likely offered an inhibitor some point their journey, options available approval criteria place cancer’s mutation status. Within large cohort patients, develop point, which makes area interest unmet need present. Herein, we review common mechanisms agents pathway, elaborate current management approaches, discuss trials attempting mitigate significant issue. We highlight for additional studies AKT1 particular.

Язык: Английский

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Endogenous Protein‐Modified Gold Nanorods as Immune‐Inert Biomodulators for Tumor‐Specific Imaging and Therapy

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Abstract Engineered modifications of nanomaterials inspired by nature hold great promise for disease‐specific imaging and therapies. However, conventional polyethylene glycol modification is limited immune system rejection. The manipulation gold nanorods (Au NRs) modified endogenous proteins (eP@Au) reported as an engineered biomodulator enhanced breast tumor therapy. results show that eP@Au NRs neither activate inflammatory factors in vitro nor elicit rejection responses vivo. Tumor‐specific exhibit a dual‐modal capability trigger mild photothermal effect under near‐infrared light irradiation, enabling highly efficient therapy tumors. Transcriptome sequencing confirmatory experiments reveal the antitumor mainly attributed to repression PI3K‐Akt/MAPK signaling pathways at molecular level. This powerful surprising situ eP‐regulated biomodulation demonstrates advantages convenient fabrication, inert immunogenicity, biocompatibility, providing alternative strategy biomedical

Язык: Английский

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Discovery of 5-Phenylthiazol-2-amine Derivatives as Novel PI4KIIIβ Inhibitors with Efficacious Antitumor Activity by Inhibiting the PI3K/AKT Axis

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

To develop novel PI4KIIIβ inhibitors and explore their antitumor activity, a series of 5-phenylthiazol-2-amine derivatives were synthesized by structural modifications PIK93. Biological assay results indicated that compounds 16 43 exhibited superior selective inhibitory antiproliferative activity than Mechanistic studies revealed the two inhibit PI3K/AKT pathway more effectively, thereby inducing cancer cell apoptosis, cycle arrest in G2/M phase autophagy. Importantly, vivo toxicity pharmacodynamics showed safety to commercially available axis inhibitor alpelisib, obviously small lung H446 xenograft models. Overall, this work highlights therapeutic potential treatment tumors, provides candidates viable drug development strategies for inhibitors.

Язык: Английский

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FGA influences invasion and metastasis of hepatocellular carcinoma through the PI3K/AKT pathway

Aging, Год журнала: 2024, Номер unknown

Опубликована: Июль 9, 2024

Fibrinogen is an important plasma protein composed of three polypeptide chains, fibrinogen alpha (FGA), beta, and gamma. Apart from being inflammation regulator, also plays a role in tumor progression. Liver cancer usually has poor prognosis, with chronic hepatitis the main cause liver cirrhosis hepatocellular carcinoma (HCC). FGA serves as serological marker for hepatitis, but its relationship remains unclear. Through bioinformatics analysis agarose gel electrophoresis, we found that was downregulated HCC correlated stage grade. By constructing both

Язык: Английский

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Epigenetic Therapy in Hormone Positive Breast Cancer: The Role of PIK3CA

Current Breast Cancer Reports, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 31, 2025

Язык: Английский

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PIK3CA gene mutation status associated with poor prognosis of breast cancer: a retrospective cohort study

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 27, 2025

PIK3CA gene mutations have been identified in various malignancies, but the prevalence of specific and their role breast cancer development remain uncertain. This study aimed to investigate clinicopathological significance prognostic impact cancer. Five common (H1047R H1047L exon 20, E542K, E545K, E545D 9) were patients using amplification refractory mutation system (ARMS) allele-specific PCR. The examined relationships between these clinicopathologic factors, such as age, HR status, Her2 lymph node involvement, distant metastasis, stage, progression-free survival (PFS). A total 40 female included this study. Twenty detected, with 12 located 20 8 9. most frequent was H1047R present 11 (14.8%). more commonly observed + (P < 0.05). No significant correlation found or Ki-67 expression. Database analysis from cBioPortal online database showed that median PFS (95%CI) unaltered group [22.93 (17.25–48.30) months] higher than altered [12.98 (8.18–18.14) months]. In study, mutant-type [13.00 (10.56–15.45) had lower wild-type [25.00 (13.46–36.55) all patients, difference = 0.004). Further, compared wild-type, associated poor addition, positive Our data public research show is a change cancer, shorter all, patients. confirmed important

Язык: Английский

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Targeting p70S6K1 Inhibits Glycated Albumin-Induced Triple-Negative Breast Cancer Cell Invasion and Overexpression of Galectin-3, a Potential Prognostic Marker in Diabetic Patients with Invasive Breast Cancer

Biomedicines, Год журнала: 2025, Номер 13(3), С. 612 - 612

Опубликована: Март 3, 2025

Background: There is an urgent need to identify new biomarkers for early diagnosis and development of therapeutic strategies diabetes mellitus (DM) patients who have invasive breast cancer (BC). We previously reported the increased activated form 70 kDa ribosomal protein S6 kinase 1 (phospho-p70S6K1) in a triple-negative BC (TNBC) cell line MDA-MB-231 exposed glycated albumin (GA) ductal carcinoma tissues from T2DM patients, compared untreated cells their non-diabetic counterparts, respectively. Objective: aimed explore function p70S6K1 GA-promoted TNBC progression. Methods: By employing small interference (si)RNA technology or blocking its activity using specific pharmacological inhibitor, we monitored invasion Transwell® inserts expression levels signaling proteins cancer-related Western blot. Results: In silico analysis revealed that high mRNA were associated with unfavorable prognosis progression advanced stages DM patients. The downregulation/blockade inhibited phosphorylation ERK1/2, downstream effector, key oncogenic protein, suppression GA-upregulated proteins, including enolase-2, capping CapG, galectin-3, cathepsin D, was observed after downregulation/blockade. Further validation analyses gene galectin-3 resulting poor overall survival disease-free survival. Conclusions: Targeting may present valuable strategy, while could serve as potential prognostic biomarker

Язык: Английский

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Strategic advancements in targeting the PI3K/AKT/mTOR pathway for Breast cancer therapy

Biochemical Pharmacology, Год журнала: 2025, Номер unknown, С. 116850 - 116850

Опубликована: Март 1, 2025

Breast cancer (BC) is a complex disease that affects millions of women worldwide. Its growing impact calls for advanced treatment strategies to improve patient outcomes. The PI3K/AKT/mTOR pathway key focus in BC therapy because it plays major role important processes like tumor growth, survival, and resistance treatment. Targeting this could lead better options present review explores how the becomes dysregulated BC, focusing on genetic changes PIK3CA mutations PTEN loss leads its aggravation. Current include use inhibitors targeting PI3K, AKT, mTOR with combination therapies showing promise overcoming drug improving effectiveness. Looking ahead, next-generation personalized plans guided by biomarker analysis may provide more accurate effective patients. Integrating these immunotherapy offers an exciting opportunity boost anti-tumor responses survival rates. This comprehensive summary current progress BC. It highlights future research directions therapeutic aimed at enhancing outcomes quality life.

Язык: Английский

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Targeting RAS and associated proteins

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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