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Cancers, Vol. 13, Pages 3612: Estrogen Receptor-Alpha and p53 Status as Regulators of AMPK and mTOR in Luminal Breast Cancer
. Das Luminal breast cancer (LBC) driven by dysregulated estrogen receptor-alpha (ERα) signaling accounts for 70% of the breast cancer cases diagnosed. Although endocrine therapy (ET) is effective against LBC, about one-third of these patients fail to respond to therapy owing to acquired or inherent resistance mechanisms. Aberrant signaling via ERα, oncogenes, growth factor receptors, and mutations in tumor suppressors such as p53 impinge on downstream regulators such as AMPK and mTOR. While both AMPK and mTOR have been reported to play important roles in determining sensitivity of LBC to ET, how the ERα-p53 crossta...
Source: Cancers - July 19, 2021 Category: Cancer & Oncology Authors: Nishant Gandhi Chetan C. Oturkar Gokul M. Das Tags: Article Source Type: research

Targeting CDK7 reverses tamoxifen resistance through regulating stemness in ER+ breast cancer
CONCLUSION: Our data indicate, for the first time, that CDK7-targeted therapy in ER+ breast cancer ameliorates tamoxifen resistance, at least in part, by inhibiting cancer stemness. Thus, targeting CDK7 might represent a potential approach for relieving tamoxifen resistance in ER+ breast cancer.PMID:35000145 | DOI:10.1007/s43440-021-00346-9
Source: Pharmacological Reports - January 9, 2022 Category: Drugs & Pharmacology Authors: Yasmin M Attia Salama A Salama Samia A Shouman Cristina Ivan Abdelrahman M Elsayed Paola Amero Cristian Rodriguez-Aguayo Gabriel Lopez-Berestein Source Type: research

Clinically relevant CHK1 inhibitors abrogate wild-type and Y537S mutant ER α expression and proliferation in luminal primary and metastatic breast cancer cells
CONCLUSIONS: CHK1 could be considered as an appealing novel pharmacological target for the treatment of luminal primary and MBCs.PMID:35418303 | DOI:10.1186/s13046-022-02360-y
Source: Cancer Control - April 14, 2022 Category: Cancer & Oncology Authors: Sara Pescatori Stefano Leone Manuela Cipolletti Stefania Bartoloni Alessandra di Masi Filippo Acconcia Source Type: research

Cancers, Vol. 14, Pages 2380: Endocrine Therapy-Resistant Breast Cancer Cells Are More Sensitive to Ceramide Kinase Inhibition and Elevated Ceramide Levels Than Therapy-Sensitive Breast Cancer Cells
In this study, we have investigated how alterations in sphingolipids promote cell survival in ET-resistant breast cancer. We have performed LC-MS-based targeted sphingolipidomics of tamoxifen-sensitive and -resistant MCF-7 breast cancer cell lines. Follow-up studies included treatments of cell lines and patient-derived xenograft organoids (PDxO) with small molecule inhibitors; cytometric analyses to measure cell death, proliferation, and apoptosis; siRNA-mediated knockdown; RT-qPCR and Western blot for gene and protein expression; targeted lipid analysis; and lipid addback experiments. We found that tamoxifen-resistant cel...
Source: Cancers - May 12, 2022 Category: Cancer & Oncology Authors: Purab Pal Alec Millner Svetlana E. Semina Rosemary J. Huggins Logan Running Diana S. Aga Debra A. Tonetti Rachel Schiff Geoffrey L. Greene G. Ekin Atilla-Gokcumen Jonna Frasor Tags: Article Source Type: research

A functional genetic screen for metabolic proteins unveils GART and the de novo purine biosynthetic pathway as novel targets for the treatment of luminal A ER α expressing primary and metastatic invasive ductal carcinoma
In conclusion, GART inhibition by LMX or other inhibitors of the de novo purine biosynthetic pathway could be a novel effective strategy for the treatment of primary and metastatic BCs.
Source: Frontiers in Endocrinology - April 18, 2023 Category: Endocrinology Source Type: research

LncRNA AGPG confers endocrine resistance in breast cancer by promoting E2F1 activity
Cancer Res. 2023 Jul 18:CAN-23-0015. doi: 10.1158/0008-5472.CAN-23-0015. Online ahead of print.ABSTRACTResistance to endocrine therapy represents a major concern for patients with estrogen receptor α positive (ERα+) breast cancer. Endocrine therapy resistance is commonly mediated by activated E2F signaling. A better understanding of the mechanisms governing E2F1 activity in resistant cells could reveal strategies for overcoming resistance. Here, we identified the long non-coding RNA (lncRNA) actin gamma 1 pseudogene 25 (AGPG) as a regulator of E2F1 activity in endocrine resistant breast cancer. Expression of EGPG was inc...
Source: Cell Research - July 18, 2023 Category: Cytology Authors: Shiyi Yu Ying Wang Xue Gong Zhehao Fan Zheng Wang Zhengyan Liang Rui Wu Binjie Cao Ning Wang Caili Bi Dan Lv Haibo Sun Source Type: research

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