The cyclinD:CDK4/6:Rb axis is dysregulated in a variety of human cancers. Targeting this pathway has proven to be a successful therapeutic approach in ER breast cancer. In this study, and preclinical breast cancer models were used to investigate the expanded use of the CDK4/6 inhibitor, abemaciclib. Using a panel of 44 breast cancer cell lines, differential sensitivity to abemaciclib was observed and was seen predominately in the luminal ER/HER2 and ER/HER2 subtypes. However, a subset of triple-negative breast cancer (TNBC) cell lines with intact Rb signaling were also found to be responsive. Equivalent levels of tumor growth inhibition were observed in ER/HER2, ER/HER2 as well as biomarker selected TNBC xenografts in response to abemaciclib. In addition, abemaciclib combined with hormonal blockade and/or HER2-targeted therapy induced significantly improved antitumor activity. CDK4/6 inhibition with abemaciclib combined with antimitotic agents, both and , did not antagonize the effect of either agent. Finally, we identified a set of Rb/E2F-regulated genes that consistently track with growth inhibitory response and constitute potential pharmacodynamic biomarkers of response to abemaciclib. Taken together, these data represent a comprehensive analysis of the preclinical activity of abemaciclib, used alone or in combination, in human breast cancer models. The subtypes most likely to respond to abemaciclib-based therapies can be identified by measurement of a specific set of biomarkers associated with increased dependency on cyclinD:CDK4/6:Rb signaling. These data support the clinical development of abemaciclib as monotherapy or as a combination partner in selected ER/HER2, HER2/ER, and TNBCs. .
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http://dx.doi.org/10.1158/1535-7163.MCT-17-0290 | DOI Listing |
Med Anthropol
December 2024
Department of Social Anthropology, University of Barcelona, Barcelona, Spain.
This research asks what is being put to the test by breast and gynecological cancer predisposition testing in Spain beyond genes or cancer. By combining document analysis and fieldwork with national healthcare professionals and drawing on the anthropology and sociology of testing, I examine how the molecular relations of these tests extend to the political economy of the national healthcare system. I show how the capacity of these tests to produce a low-risk collective has paradoxical consequences for the political economy of the national healthcare system, unsettling professionals' concerns and spotlighting what is prioritized in personalized medicine strategies.
View Article and Find Full Text PDFDrug Dev Res
February 2025
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Five series of new 1,3,4-thiadiazole hybrids were designed and synthesized as promising EGFR inhibitors. Three human cancer cell lines were employed for testing each hybrid's in vitro antiproliferative efficacy; colon HCT-116, liver HepG-2 and breast MCF-7 using MTT assay. Comparing compound 9a to the reference doxorubicin, 9a shown superior activity to that of Dox with respect to MCF-7 (IC 3.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Translational Medicine, Clinical Research Centre, Skåne University Hospital, Lund University, Malmö, Sweden.
Berberine, an isoquinoline alkaloid derived from various medicinal plants, emerges as a potential therapeutic agent against diverse human diseases. It has particularly shown notable anticancer efficacy against breast, colorectal, lung, prostate, and liver cancer. Berberine results in inhibition of cancer cell proliferation, induction of apoptosis, and suppressing angiogenesis, positioning it as a versatile, multitargeted therapeutic tool against cancer.
View Article and Find Full Text PDFJ Mater Chem B
December 2024
ICGM, University of Montpellier, UMR-CNRS 5253, 34293 Montpellier, France.
We report the synthesis of multifunctional periodic mesoporous organosilica nanoparticles (PMO NPs) with substantial two-photon absorption properties and targeting capability for two-photon excitation fluorescence (TPEF) and photodynamic therapy (TPE-PDT). Prepared using an adapted sol-gel synthesis, the nanoplatforms integrated two silylated chromophores in their three-dimensional matrix to maximize non-radiative Förster resonance energy transfer from a high two-photon absorption fluorophore donor to a porphyrin derivative acceptor, leading to an enhanced generation of reactive oxygen species. Combinations of biodegradable and non-biodegradable bis(triethoxysilyl)alkoxysilanes were employed for the synthesis of the NPs, and the corresponding photophysical studies revealed high efficiency levels of FRET.
View Article and Find Full Text PDFFront Glob Womens Health
December 2024
WHO Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
[This corrects the article DOI: 10.3389/fgwh.2024.
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