PIK3CA mutation confers resistance to chemotherapy in triple-negative breast cancer by inhibiting apoptosis and activating the PI3K/AKT/mTOR signaling pathway DOI Open Access

Huayu Hu,

Junyong Zhu, Yuting Zhong

и другие.

Annals of Translational Medicine, Год журнала: 2021, Номер 9(5), С. 410 - 410

Опубликована: Март 1, 2021

Triple-negative breast cancer (TNBC) is a malignant subtype of cancer, the main treatments for which are chemotherapy and surgery. PIK3CA an oncogene that encodes p110α subunit class IA PI3K to regulate cell proliferation apoptosis. Some reports have observed neoadjuvant (NAC) poor pathological complete response (pCR) rates in TNBC with mutation. This study aimed explore mechanism how mutant alters chemotherapeutic susceptibility TNBC.TNBC lines (MDA-MB-231 MDA-MB-468) gene mutations (E545K H1047R regions) overexpression were established by transfection. NOD/SCID mice used vivo experiments. Epirubicin was as agent. Cell viability, cycle, apoptosis, Transwell assays conducted phenotype analysis. Western blot, quantitative reverse transcription-polymerase chain reaction, immunohistochemistry detect protein expression levels. A clinical analysis 50 patients also performed.Cell viability showed mutation promoted growth conferred enhanced migratory phenotype. cycle apoptosis moderately improved ability cells remarkably inhibited their After epirubicin therapy, proportion early apoptotic decreased among Further, xenograft tumors grew faster injected mutated than control group, suggesting caused resistance. Importantly, western blot immunohistochemical mouse groups exhibited different levels apoptosis-related markers (Xiap, Bcl-2, Caspase 3) proteins associated PI3K/AKT/mTOR pathway (p110α, AKT, p-AKT, mTOR, p-mTOR, p-4E-BP1, p-p70S6K, Pten). Moreover, prognostic indicated might be linked relapse death.PIK3CA confers resistance inhibiting activating signaling pathway.

Язык: Английский

Triple-negative breast cancer therapeutic resistance: Where is the Achilles' heel? DOI
Xupeng Bai, Jie Ni, Julia Beretov

и другие.

Cancer Letters, Год журнала: 2020, Номер 497, С. 100 - 111

Опубликована: Окт. 16, 2020

Язык: Английский

Процитировано

178
The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer DOI

Zimei Yang,

Qiuhua Zhang,

Linghong Yu

и другие.

Journal of Ethnopharmacology, Год журнала: 2020, Номер 264, С. 113249 - 113249

Опубликована: Авг. 15, 2020

Язык: Английский

Процитировано

170
Breast Cancer Type Classification Using Machine Learning DOI Open Access
Jiande Wu, Chindo Hicks

Journal of Personalized Medicine, Год журнала: 2021, Номер 11(2), С. 61 - 61

Опубликована: Янв. 20, 2021

Background: Breast cancer is a heterogeneous disease defined by molecular types and subtypes. Advances in genomic research have enabled use of precision medicine clinical management breast cancer. A critical unmet medical need distinguishing triple negative cancer, the most aggressive lethal form from non-triple Here we propose machine learning (ML) approach for classification patients using gene expression data. Methods: We performed analysis RNA-Sequence data 110 992 tumor samples The Cancer Genome Atlas to select features (genes) used development validation models. evaluated four different models including Support Vector Machines, K-nearest neighbor, Naïve Bayes Decision tree selected at threshold levels train classifying two For performance evaluation validation, proposed methods were applied independent datasets. Results: Among ML algorithms evaluated, Machine algorithm was able classify more accurately into had less misclassification errors than other three evaluated. Conclusions: prediction results show that are efficient can be types.

Язык: Английский

Процитировано

161
Overcoming cancer chemotherapy resistance by the induction of ferroptosis DOI
Yumin Wang,

Xiaorui Wu,

Ren Zhao

и другие.

Drug Resistance Updates, Год журнала: 2022, Номер 66, С. 100916 - 100916

Опубликована: Дек. 29, 2022

Язык: Английский

Процитировано

158
Exosomes and breast cancer drug resistance DOI Creative Commons

Xingli Dong,

Xupeng Bai, Jie Ni

и другие.

Cell Death and Disease, Год журнала: 2020, Номер 11(11)

Опубликована: Ноя. 17, 2020

Abstract Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors tumor microenvironment, play an important role BC progression. With in-depth understanding heterogeneity, emerging exosomes drug has attracted extensive attention. The functional proteins or non-coding RNAs contained secreted from and stromal cells mediate by regulating efflux metabolism, pro-survival signaling, epithelial–mesenchymal transition, stem-like property, microenvironmental remodeling. In this review, we summarize underlying associations between discuss unique biogenesis exosomes, change exosome cargo, pattern release response to treatment. Moreover, propose candidate biomarker predicting monitoring therapeutic potential target carrier reverse BC.

Язык: Английский

Процитировано

148
Mechanisms of Taxane Resistance DOI Open Access

Sara Maloney,

Camden A. Hoover,

Lorena V. Morejon-Lasso

и другие.

Cancers, Год журнала: 2020, Номер 12(11), С. 3323 - 3323

Опубликована: Ноя. 10, 2020

The taxane family of chemotherapy drugs has been used to treat a variety mostly epithelial-derived tumors and remain the first-line treatment for some cancers. Despite improved survival time reduction tumor size observed in patients, many have no response or develop resistance over time. Taxane is multi-faceted involves multiple pathways proliferation, apoptosis, metabolism, transport foreign substances. In this review, we dive deeper into hypothesized mechanisms from research during last decade, with focus on cancer types that use taxanes as but frequently them. Furthermore, will discuss current clinical inhibitors those yet be approved target key proteins aim reverse combination individually. Lastly, highlight biomarkers, specific genes monitored expression correlated taxanes, mentioning currently being should adopted. future directions involve more personalized approaches by tailoring drug–inhibitor combinations alternatives depending levels biomarkers. We hope review identify gaps knowledge surrounding trials can overcome.

Язык: Английский

Процитировано

142
Triple Negative Breast Cancer Treatment Options and Limitations: Future Outlook DOI Creative Commons
Onyinyechi Obidiro, Gantumur Battogtokh, Emmanuel O. Akala

и другие.

Pharmaceutics, Год журнала: 2023, Номер 15(7), С. 1796 - 1796

Опубликована: Июнь 23, 2023

Triple negative breast cancer (TNBC) has a expression of estrogen receptors (ER), progesterone (PR), and human epidermal growth factor (HER2). The survival rate for TNBC is generally worse than other subtypes. treatment made significant advances, but certain limitations remain. Treatment can be challenging since the disease various molecular A variety options are available, such as chemotherapy, immunotherapy, radiotherapy, surgery. Chemotherapy most common these options. treated with systemic chemotherapy using drugs anthracyclines taxanes in neoadjuvant or adjuvant settings. Developing resistance to anticancer off-target toxicity primary hindrances chemotherapeutic solutions cancer. It imperative that researchers, clinicians, pharmaceutical companies work together develop effective TNBC. Several studies have suggested nanotechnology potential solution problem suboptimal treatment. In this review, we summarized possible TNBC, including targeted therapy, combination nanoparticle-based some future. Moreover, gave general information about terms its characteristics aggressiveness.

Язык: Английский

Процитировано

132
Stimuli-responsive ferroptosis for cancer therapy DOI
Nayeon Kang, Subin Son, Sunhong Min

и другие.

Chemical Society Reviews, Год журнала: 2023, Номер 52(12), С. 3955 - 3972

Опубликована: Янв. 1, 2023

This review highlights recent advances in the utilization of various endogenous and exogenous stimuli to activate nanocarrier-based ferroptosis cancer therapy that can be effective treating conventional drug-resistant tumors.

Язык: Английский

Процитировано

120
Evaluation of Racial/Ethnic Differences in Treatment and Mortality Among Women With Triple-Negative Breast Cancer DOI
Beomyoung Cho, Yunan Han, Min Lian

и другие.

JAMA Oncology, Год журнала: 2021, Номер 7(7), С. 1016 - 1016

Опубликована: Май 13, 2021

To our knowledge, there is no consensus regarding differences in treatment and mortality between non-Hispanic African American White women with triple-negative breast cancer (TNBC). Little known about whether racial disparities vary by sociodemographic, clinical, neighborhood factors.To examine the clinical outcomes a nationally representative cohort of patients TNBC further contributions factors to outcome disparities.This population-based, retrospective study included 23 123 who received diagnosis nonmetastatic January 1, 2010, December 31, 2015, followed up through 2016, identified from Surveillance, Epidemiology, End Results data set. The was conducted July 2019 November 2020. analyses were performed June 2020.Race ethnicity, including race.Using logistic regression analysis competing risk analysis, we estimated odds ratios (ORs) receipt hazard (HRs) compared patients.Of 213 participants, 5881 (25.3%) 17 332 (74.7%) women. Compared patients, had lower receiving surgery (OR, 0.69; 95% CI, 0.60-0.79) chemotherapy 0.89; 0.81-0.99) after adjustment for clinicopathologic, county-level factors. During 43-month follow-up, 3276 (14.2%) died cancer. HR 1.28 (95% 1.18-1.38) individuals sociodemographic Further clinicopathological reduced 1.16 1.06-1.25). This association observed living socioeconomically less deprived counties (HR, 1.26; 1.14-1.39), urban 1.21; 1.11-1.32), having stage II 1.19; 1.02-1.39) or III 1.15; 1.01-1.31) tumors that treated chemotherapy, younger than 65 years 1.24; 1.12-1.37).In this study, significantly higher their counterparts, which partially explained chemotherapy.

Язык: Английский

Процитировано

107
Patient‐Derived Organoids Can Guide Personalized‐Therapies for Patients with Advanced Breast Cancer DOI
Ping Chen, Xu Zhang, Ren‐Bo Ding

и другие.

Advanced Science, Год журнала: 2021, Номер 8(22)

Опубликована: Окт. 4, 2021

Most breast cancers at an advanced stage exhibit aggressive nature, and there is a lack of effective anticancer options. Herein, the development patient-derived organoids (PDOs) described as real-time platform to explore feasibility tailored treatment for refractory cancers. PDOs are successfully generated from cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures predict improved distant relapse-free survival invasive with adjuvant chemotherapy. It further demonstrated that PDO pharmaco-phenotyping reflects previous responses corresponding patients. Finally, clinical case studies, all patients who receive least one drug predicate be sensitive by achieve good responses. Altogether, model developed evaluating patient-specific sensitivity in vitro, which can guide personal decisions terminal stage.

Язык: Английский

Процитировано

104