Hypoxia-related biological markers as predictors of epirubicin-based treatment responsiveness and resistance in locally advanced breast cancer

Milani, Manuela; Venturini, Sergio; Bonardi, S; Allevi, Giovanni; Strina, Carla; Cappelletti, Maria Rosa; Corona, Silvia Paola; Aguggini, Sergio; Bottini, Alberto; Berruti, Alfredo; Jubb, Adrian M.; Campo, Leticia; Harris, Adrian L.; Gatter, Kevin C.; Fox, Stephen B.; Generali, Daniele; Roviello, Giandomenico

doi:10.18632/oncotarget.20239

Cited by 8 publications

(7 citation statements)

References 44 publications

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“…CAV1, an integral structural component of caveolae, is a direct target of HIF-1. Numerous studies have recently demonstrated that hypoxia-associated biological markers can be used as predictors of treatment, metastasis and prognosis in various types of cancer, including breast, lung and colorectal cancer (15–17). The present study revealed that HIF-1α and CAV1 were significantly upregulated in patients with IDH-wild type GBM.…”

Section: Discussionmentioning

confidence: 99%

Clinical implications of hypoxia‑inducible factor‑1α and caveolin‑1 overexpression in isocitrate dehydrogenase‑wild type glioblastoma multiforme

et al. 2019

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Glioblastoma multiforme (GBM) is the most common type of primary brain tumour in adults, and presents a very low survival rate. Isocitrate dehydrogenase (IDH)1/2 mutations have been found in ~12% of glioblastomas and are associated with long-term GBM survival. However, the risk factors that influence the prognosis of IDH-wild type GBM remain unclear. Hypoxia-inducible factor (HIF)-1α, an important oxygen-regulated transcription factor, has been demonstrated to serve a crucial role in tumour development and to be associated with a poor prognosis. In addition, caveolin-1 (CAV1) is a plasma membrane organizing protein, the expression of which can also be regulated by a hypoxic microenvironment. The present study therefore aimed to examine the expression levels of HIF-1α and CAV1, and their association with GBM prognosis. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to analyse the expression levels of HIF-1α and CAV1 in paired GBM tumour and adjacent non-tumour tissues. Immunohistochemistry was used to analyse the expression of the two proteins in paraffin-embedded tissues obtained from 42 patients with IDH-wild type GBM. Statistical analyses were performed to examine the correlation between HIF-1α and CAV1 expression and patient prognosis. The results revealed hat the expression levels of HIF-1α and CAV1 were upregulated in IDH-wild type GBM tissues compared to their paired non-tumour tissues (P<0.001). The expression of CAV1 was significantly correlated with high HIF-1α expression (P<0.01). In addition, overexpression of HIF-1α and CAV1 was markedly associated with a poor prognosis (P<0.001). In conclusion, HIF-1α and CAV1 may represent potential biomarkers for IDH-wild type GBM prognosis and potential targets for the development of therapies extending GBM survival.

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Section: Discussionmentioning

confidence: 99%

Clinical implications of hypoxia‑inducible factor‑1α and caveolin‑1 overexpression in isocitrate dehydrogenase‑wild type glioblastoma multiforme

et al. 2019

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“…It is generally acknowledged that tumor hypoxia and multiple HIF-related markers predict worse response to chemoradiotherapy, and neoadjuvant studies have shown lower pathologic complete response (pCR) rates in patients with high baseline HIF expression (22,(103)(104)(105).…”

Section: Predictive Markersmentioning

confidence: 99%

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Heer¹,

Jalving²,

Harris³

2020

Journal of Clinical Investigation

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219

146

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Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis and metabolic rewiring are well-established drivers of breast cancer aggressiveness, therapy resistance, and poor prognosis. Targeting of HIF and its downstream targets in angiogenesis and metabolism has been unsuccessful so far in the breast cancer clinical setting, with major unresolved challenges residing in target selection, development of robust biomarkers for response prediction, and understanding and harnessing escape mechanisms. This Review discusses the pathophysiological role of HIFs, angiogenesis, and metabolism in breast cancer and the challenges of targeting these features in breast cancer patients. Rational therapeutic combinations, especially with immunotherapy and endocrine therapy, seem most promising in the clinical exploitation of the intricate interplay of HIFs, angiogenesis, and metabolism in breast cancer cells and the tumor microenvironment.

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“…Recent studies have shown that the contribution of CK2 and PIM-1 kinases to the regulation of transcription, differentiation, or signaling of DNA damage/repair systems is achieved by regulating survival pathways and hypoxia [ 23 ]. The activity of both CK2 and PIM-1 has been demonstrated to be elevated in hypoxia, which increases HIF-1 transcriptional activity (hypoxia-induced factor), whereas under normoxia, this factor is degraded [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anticancer Activity of Novel Dual Inhibitors of Human Protein Kinases CK2 and PIM-1

et al. 2023

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CK2 and PIM-1 are serine/threonine kinases involved in the regulation of many essential processes, such as proliferation, differentiation, and apoptosis. Inhibition of CK2 and PIM-1 kinase activity has been shown to significantly reduce the viability of cancer cells by inducing apoptosis. A series of novel amino alcohol derivatives of parental DMAT were designed and synthesized as potent dual CK2/PIM-1 inhibitors. Concomitantly with the inhibition studies toward recombinant CK2 and PIM-1, the influence of the obtained compounds on the viability of three human carcinoma cell lines, i.e., acute lymphoblastic leukemia (CCRF-CEM), human chronic myelogenous leukemia (K-562), and breast cancer (MCF-7), as well as non-cancerous cells (Vero), was evaluated using an MTT assay. Induction of apoptosis and cell cycle progression after treatment with the most active compound and a lead compound were studied by flow-cytometry-based assay. Additionally, autophagy induction in K-562 cells and intracellular inhibition of CK2 and PIM-1 in all the tested cell lines were evaluated by qualitative/quantitative fluorescence-based assay and Western blot method, respectively. Among the newly developed inhibitors, 1,1,1-trifluoro-3-[(4,5,6,7-tetrabromo-1H-benzimidazol-2-yl)amino]propan-2-ol demonstrates the highest selectivity and the most prominent proapoptotic properties towards the studied cancer cells, especially towards acute lymphoblastic leukemia, in addition to inducing autophagy in K-562 cells.

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Hypoxia-related biological markers as predictors of epirubicin-based treatment responsiveness and resistance in locally advanced breast cancer

Cited by 8 publications

References 44 publications

Clinical implications of hypoxia‑inducible factor‑1α and caveolin‑1 overexpression in isocitrate dehydrogenase‑wild type glioblastoma multiforme

Clinical implications of hypoxia‑inducible factor‑1α and caveolin‑1 overexpression in isocitrate dehydrogenase‑wild type glioblastoma multiforme

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Synthesis and Anticancer Activity of Novel Dual Inhibitors of Human Protein Kinases CK2 and PIM-1

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