Inhibition of platelet‑derived growth factor receptor synergistically increases the pharmacological effect of tamoxifen in estrogen receptor α positive breast cancer

Kim, Sang-Min; You, Daeun; Jeong, Yu Jeong; Yoon, Sun Young; Kim, Sung‐A; Lee, Jeong Eon

doi:10.3892/ol.2021.12555

Cited by 14 publications

(13 citation statements)

References 26 publications

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“…Compound 43 caused relatively little toxicity in all tested cell lines, especially with IC 50 > 180 μM in MCF7, respectively, in MCF7 cell lines. 44,45 Permeability and Metabolic Stability. We further evaluated the potential utility of MTH1 activators for their ability to enter cells and resist metabolic degradation using standard CaCO-2 and mouse liver microsome assays.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Enhancing Repair of Oxidative DNA Damage with Small-Molecule Activators of MTH1

et al. 2022

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Impaired DNA repair activity has been shown to greatly increase rates of cancer clinically. It has been hypothesized that upregulating repair activity in susceptible individuals may be a useful strategy for inhibiting tumorigenesis. Here, we report that selected tyrosine kinase (TK) inhibitors including nilotinib, employed clinically in the treatment of chronic myeloid leukemia, are activators of the repair enzyme Human MutT Homolog 1 (MTH1). MTH1 cleanses the oxidatively damaged cellular nucleotide pool by hydrolyzing the oxidized nucleotide 8-oxo-2'-deoxyguanosine (8-oxo-dG)TP, which is a highly mutagenic lesion when incorporated into DNA. Structural optimization of analogues of TK inhibitors resulted in compounds such as SU0448, which induces 1000 ± 100% activation of MTH1 at 10 μM and 410 ± 60% at 5 μM. The compounds are found to increase the activity of the endogenous enzyme, and at least one (SU0448) decreases levels of 8-oxo-dG in cellular DNA. The results suggest the possibility of using MTH1 activators to decrease the frequency of mutagenic nucleotides entering DNA, which may be a promising strategy to suppress tumorigenesis in individuals with elevated cancer risks.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Enhancing Repair of Oxidative DNA Damage with Small-Molecule Activators of MTH1

et al. 2022

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“…SDF-1 is an important niche factor in IL-7-expressing CAFs, indicating that the CXCL12 (SDF-1)/CXCR4 pathway may be a useful anti-cancer stem cell therapeutic (anti-CSC) target [ 42 ]. PDGF-BB is one of the factors that has a significant impact on the survival rate in ER+ breast tumors [ 43 ]. PDGFR inhibitors (ponatinib or sunitinib) are used to block PDGF-BB signaling in combination with tamoxifen.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Breast Cancer: The Cytokinome of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, and Stem Cell Markers

Tarek

El-Sayed

Woodward

et al. 2022

CIMB

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Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed a significantly higher expression of various cytokines than in non-IBC patients. In vitro cell culture models of non-IBC and IBC cell lines were grown in media conditioned with and/without WF for 48 h. Afterwards, we assessed cell viability, the expression of CSCs and EMT-specific genes, and tumor invasion. Genes associated with CSCs properties and EMT markers were regulated in cells seeded in media conditioned by WF. IBC-WF exhibited a greater potential for inducing IBC cell invasion than non-IBC cells. The present study demonstrates the role of the post-surgical tumor cavity in IBC recurrence and metastasis.

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“…The PDGF family has five isoforms (PDGF AA, BB, AB, CC, and DD) that bind to two RTKs, PDGFRα and PDGFRβ. After activation of PDGFRα and β, they promote cell proliferation, migration and survival through initiating signaling pathway with the inclusion of the extracellular signal-regulated kinase 1/2 (ERK) and phosphatidylinositol 3-kinase (PI3K)/AKT [77].…”

Section: Platelet Derived Growth Factor Receptormentioning

confidence: 99%

The Role of Kinase Inhibitors in Cancer Therapies

Kursunluoglu¹,

Erdogan²,

Cagatay³

et al. 2021

Protein Kinases - Promising Targets for Anticancer Drug Research

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Protein kinases are enzymes that transfer a phosphate group to the threonine, serine, or tyrosine residues of the target protein, regulating its activity. The activity of these enzymes are very important and strictly regulated in the cell as they promote cell proliferation, survival, and migration. In the case of any dysregulation of these enzymes, they can be associated with cancer initiation and progression. Small-molecule kinase inhibitors approved by the FDA for their improved clinical benefits are currently used in targeted therapy for the treatment of various cancers. So far, there are 62 FDA-approved therapeutic agents targeting different protein kinases, eight of which were approved in 2020. Today, kinase inhibitors are used as FDA approved cancer agents and newly developed ones are evaluated in clinical trials. Those protein kinase inhibitors can be grouped as growth factor receptor inhibitors, Ras/Raf/Mek inhibitors, phosphoinositide 3-kinase (PI3K) and cyclin dependent kinase inhibitors, other targets, and agents such as protein kinase c and 3 phosphoinositide-dependent kinase 1. In this chapter, these kinases, their pathways, and their inhibitors will be discussed in detail.

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Inhibition of platelet‑derived growth factor receptor synergistically increases the pharmacological effect of tamoxifen in estrogen receptor α positive breast cancer

Cited by 14 publications

References 26 publications

Enhancing Repair of Oxidative DNA Damage with Small-Molecule Activators of MTH1

Enhancing Repair of Oxidative DNA Damage with Small-Molecule Activators of MTH1

Inflammatory Breast Cancer: The Cytokinome of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, and Stem Cell Markers

The Role of Kinase Inhibitors in Cancer Therapies

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