Viewing the Eph receptors with a focus on breast cancer heterogeneity

Nikas, Ilias P.; Ryu, Han Suk; Theocharis, Stamatios

doi:10.1016/j.canlet.2018.07.030

Cited by 33 publications

(28 citation statements)

References 171 publications

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“…Therefore, we have focused on EphB4 as an alternative target, especially for Her-2 negative breast cancer patients. Members of the Ephrin receptor family have already been indicated for their role in carcinogenesis in various types of tumors [ 10 , 11 , 12 , 13 , 14 , 18 , 19 , 20 ]. As a result, EphA2 is highly ranked in the NIH’s list for potential cell surface antigen targets for cancer treatment [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…EphB4 and its ligand Ephrin B2 are involved in mammary morphogenesis in normal breast tissue [ 9 ]. EphB4 is also reported to be abundantly present in a variety of solid tumors, including colorectal cancer, prostate cancer, gastric cancer, and breast cancer, suggesting a common mechanism in carcinogenesis [ 10 , 11 , 12 , 13 , 14 ]. However, the role of EphB4 in tumorigenesis is way more complicated than in normal tissue, with tumor suppressing as well as tumor promoting effects [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of EphB4 as Target for Image-Guided Surgery of Breast Cancer

et al. 2020

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Background: Targeted image-guided surgery is based on the detection of tumor cells after administration of a radio-active or fluorescent tracer. Hence, enhanced binding of a tracer to tumor tissue compared to healthy tissue is crucial. Various tumor antigens have been evaluated as possible targets for image-guided surgery of breast cancer, with mixed results. Methods: In this study we have evaluated tyrosine kinase receptor EphB4, a member from the Eph tyrosine kinase receptor family, as a possible target for image-guided surgery of breast cancers. Two independent tissue micro arrays, consisting of matched sets of tumor and normal breast tissue, were stained for EphB4 by immunohistochemistry. The intensity of staining and the percentage of stained cells were scored by two independent investigators. Results: Immunohistochemical staining for EphB4 shows that breast cancer cells display enhanced membranous expression compared to adjacent normal breast tissue. The enhanced tumor staining is not associated with clinical variables like age of the patient or stage or subtype of the tumor, including Her2-status. Conclusion: These data suggest that EphB4 is a promising candidate for targeted image-guided surgery of breast cancer, especially for Her2 negative cases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of EphB4 as Target for Image-Guided Surgery of Breast Cancer

et al. 2020

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“…Decreased viability of human cervical carcinoma HeLa and osteosarcoma U2OS cells [7] Decreased proliferation of colon adenocarcinoma HCT-116 cells; induction of apoptosis [8] d-ring fused 1,2,3-thiadiazole dehydroepiandrosterone (DHEA) derivatives Unknown Decreased proliferation, ability to form colonies and migrate of human breast cancer T47D cells; induction of apoptosis [9] Reduced tumor growth and metastatic ability in T47D xenografts [10] Pyrazole oxime derivatives bearing 1,2,3-thiadiazole…”

Section: Hsp90mentioning

confidence: 99%

“…Further analysis revealed that compound 25 significantly inhibited the ability of T47D cells to form colonies and migrate as well as induced apoptosis. It also increased the phosphorylation level of ephrin (Eph) receptors, EphA2 and EphB3, proteins involved in the pathogenesis of breast cancer [ 9 ]. Clearly further studies are required to elucidate whether the deregulation of EphA2 and EphB3 contributes to the anticancer activity of compound 25 or not.…”

Section: Derivatives Of 123-thiadiazolementioning

confidence: 99%

Thiadiazole derivatives as anticancer agents

Szeliga

2020

Pharmacol. Rep

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In spite of substantial progress made toward understanding cancer pathogenesis, this disease remains one of the leading causes of mortality. Thus, there is an urgent need to develop novel, more effective anticancer therapeutics. Thiadiazole ring is a versatile scaffold widely studied in medicinal chemistry. Mesoionic character of this ring allows thiadiazole-containing compounds to cross cellular membrane and interact strongly with biological targets. Consequently, these compounds exert a broad spectrum of biological activities. This review presents the current state of knowledge on thiadiazole derivatives that demonstrate in vitro and/or in vivo efficacy across the cancer models with an emphasis on targets of action. The influence of the substituent on the compounds’ activity is depicted. Furthermore, the results from clinical trials assessing thiadiazole-containing drugs in cancer patients are summarized.

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“…The endothelial cells and pericytes of blood vessels, cancer-associated fibroblasts (CAFs), various immune and inflammatory cells, and extracellular matrix (ECM) all interact with the tumor cells and influence cancer progression, survival, and response to therapy [3,4]. Notably, cancer is not a single disease yet appears heterogeneous among individuals (intertumor heterogeneity), also within its own tumor mass in each affected individual (intratumor heterogeneity) [5,6]. Apart from the tumor microenvironment, cancer stem cells (CSCs) are also a…”

Section: Introductionmentioning

confidence: 99%

Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

Nikas

Themistocleous

Paschou

et al. 2019

Cells

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Cancer, a heterogeneous disease composed of tumor cells and microenvironment, is driven by deregulated processes such as increased proliferation, invasion, metastasis, angiogenesis, and evasion of apoptosis. Alternative splicing, a mechanism led by splicing factors, is implicated in carcinogenesis by affecting any of the processes above. Accumulating evidence suggests that serine-arginine protein kinase 1 (SRPK1), an enzyme that phosphorylates splicing factors rich in serine/arginine domains, has a prognostic and potential predictive role in various cancers. Its upregulation is correlated with higher tumor staging, grading, and shorter survival. SRPK1 is also highly expressed in the premalignant changes of some cancers, showing a potential role in the early steps of carcinogenesis. Of interest, its downregulation in preclinical models has mostly been tumor-suppressive and affected diverse processes heterogeneously, depending on the oncogenic context. In addition, targeting SRPK1 has enhanced sensitivity to platinum-based chemotherapy in some cancers. Lastly, its aberrant function has been noted not only in cancer cells but also in the endothelial cells of the microenvironment. Although the aforementioned evidence seems promising, more studies are needed to reinforce the use of SRPK1 inhibitors in clinical trials. major area of research in the field of intratumor heterogeneity, while their presence is associated with cancer recurrence, metastasis, and resistance to chemotherapy [7].Cancer prognosis depends on multiple factors that affect survival. Tumor staging, traditionally performed with the TNM system, is the most important prognostic factor. It refers to the size of the tumor (T), also the extent of its spread to the regional lymph nodes (N) or distant metastatic sites (M) [8,9]. Grading refers to the histologic picture of the tumor, more specifically, how closely it looks compared to the normal tissue it derives from (differentiation) [10,11]. Both the presence of distant metastases (e.g., in lungs, brain, liver, bones) and poor differentiation are associated with a dismal prognosis [9,11]. The molecular subtype of specific cancers is also critical for cancer survival. For instance, breast cancer has diverse intrinsic subtypes-luminal A and B, human epidermal growth factor receptor 2-enriched (HER2-enriched), and basal-like-that directly impact prognosis [12][13][14]. Luminal breast cancers are most commonly hormone-positive, overexpressing estrogen receptors (ER), and are associated with a better prognosis than HER2-enriched or basal-like breast cancers (BLBCs) [12][13][14][15]. BLBCs, which most commonly present with a triple-negative phenotype, have been linked with the worst prognosis and highest metastatic potential of all breast cancer molecular subtypes [13,16,17].Alternative splicing is the process that removes introns and adds exons in various combinations resulting in multiple mRNA products hence protein transcripts. As a result, it maintains the protein diversity and cellular homeostasis [18]. The...

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Viewing the Eph receptors with a focus on breast cancer heterogeneity

Cited by 33 publications

References 171 publications

Evaluation of EphB4 as Target for Image-Guided Surgery of Breast Cancer

Evaluation of EphB4 as Target for Image-Guided Surgery of Breast Cancer

Thiadiazole derivatives as anticancer agents

Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

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