Developments in the Management of Metastatic HER2-Positive Breast Cancer: A Review

Lebert, Julie M.; Lilly, Evan

doi:10.3390/curroncol29040208

Cited by 15 publications

(9 citation statements)

References 48 publications

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“…Since protein kinases are fundamental players in the molecular mechanisms underlying cell signalling and their deregulation leads to development and progression of various types of cancer [ 4 ], they have been pursued as key therapeutic targets. For example, the receptor tyrosine kinase HER2 is targeted by the monoclonal antibody therapy trastuzumab in HER2 breast cancers [ 5 ], CDK4/6 by palbociclib in endocrine therapy-resistant luminal breast cancers [ 6 ] and particular FGFR family members represent potential therapeutic targets in subsets of luminal and triple negative breast cancer patients [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Since protein kinases are fundamental players in the molecular Page 2 of 15 de Castro Ferezin et al Cell Communication and Signaling (2022) 20:197 mechanisms underlying cell signalling and their deregulation leads to development and progression of various types of cancer [4], they have been pursued as key therapeutic targets. For example, the receptor tyrosine kinase HER2 is targeted by the monoclonal antibody therapy trastuzumab in HER2 breast cancers [5], CDK4/6 by palbociclib in endocrine therapy-resistant luminal breast cancers [6] and particular FGFR family members represent potential therapeutic targets in subsets of luminal and triple negative breast cancer patients [7]. Despite the fact that specific protein kinases represent some of the most well-known targets for cancer treatment, a considerable proportion of the protein kinase family, often referred to as the 'dark kinome' , remains poorly characterized and warrants further investigation [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Identification of biological pathways and processes regulated by NEK5 in breast epithelial cells via an integrated proteomic approach

Ferezin

Sian

et al. 2022

Cell Commun Signal

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Specific members of the Nima-Related Kinase (NEK) family have been linked to cancer development and progression, and a role for NEK5, one of the least studied members, in breast cancer has recently been proposed. However, while NEK5 is known to regulate centrosome separation and mitotic spindle assembly, NEK5 signalling mechanisms and function in this malignancy require further characterization. To this end, we established a model system featuring overexpression of NEK5 in the immortalized breast epithelial cell line MCF-10A. MCF-10A cells overexpressing NEK5 exhibited an increase in clonogenicity under monolayer conditions and enhanced acinar size and abnormal morphology in 3D Matrigel culture. Interestingly, they also exhibited a marked reduction in Src activation and downstream signalling. To interrogate NEK5 signalling and function in an unbiased manner, we applied a variety of MS-based proteomic approaches. Determination of the NEK5 interactome by Bio-ID identified a variety of protein classes including the kinesins KIF2C and KIF22, the mitochondrial proteins TFAM, TFB2M and MFN2, RhoH effectors and the negative regulator of Src, CSK. Characterization of proteins and phosphosites modulated upon NEK5 overexpression by global MS-based (phospho)proteomic profiling revealed impact on the cell cycle, DNA synthesis and repair, Rho GTPase signalling, the microtubule cytoskeleton and hemidesmosome assembly. Overall, the study indicates that NEK5 impacts diverse pathways and processes in breast epithelial cells, and likely plays a multifaceted role in breast cancer development and progression.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of biological pathways and processes regulated by NEK5 in breast epithelial cells via an integrated proteomic approach

Ferezin

Sian

et al. 2022

Cell Commun Signal

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“…Breast cancer is a type of malignant tumor with the highest morbidity and mortality in women 6 . HER‐2 overexpression is present in 15%–20% of women with breast cancer and is associated with poor prognosis 7 . Anti‐HER‐2 therapy has dramatically improved the prognosis of HER‐2‐positive breast cancer patients with a median survival of nearly 5 years and low distant recurrence rate 8–10 .…”

Section: Discussionmentioning

confidence: 99%

Inetetamab in combination with rapamycin and chemotherapy for trastuzumab‐treated metastatic human epidermal growth factor receptor 2‐positive breast cancer with abnormal activation of PI3K/Akt/mTOR pathway

Wang

Jiang

et al. 2023

Cancer Reports

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BackgroundHuman epidermal growth factor receptor 2 (HER2) overexpression is an independent prognostic factor of poor prognosis and a predictor of efficacy of anti‐HER2 therapy. A limited number of patients can receive standard second‐line therapy (DS‐8201 or T‐DM1) for metastatic HER2‐positive in some parts of the world, including China, due to many factors, such as cost–benefit ratios.CaseA 51‐year‐old premenopausal woman was diagnosed with HER2‐positive breast cancer. The pathological stage was ypT3N2M0 and stage IIIA. Trastuzumab targeted therapy combined with goserelin depot was started along with letrozole endocrine therapy. After eight courses of treatment, magnetic resonance imaging (MRI) examination revealed new multiple metastases in the liver, and progression disease (PD) was evaluated. Due to abnormal activation of the phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway in the patient, treatment was changed to the mammalian target of rapamycin (mTOR) inhibitor combined with the anti‐HER‐2 agents inetetamab and paclitaxel, while partial response (PR) was evaluated after 6 cycles of treatment. As the patient was hormone receptor (HR) positive, treatment was changed to the inetetamab + rapamycin + exemestane regimen. The lesion continued to shrink and PR was evaluated for 8 cycles. The original regimen was continued, PR was evaluated after 12 courses of treatment. The abdominal MRI performed showed an increase in the volume of intrahepatic multiple metastatic tumor lesion. Efficacy was used to assess for PD and the progression‐free survival (PFS) was 317 days.ConclusionA phosphatidylinositol‐4, 5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) mutation in trastuzumab‐treated metastatic HER2‐positive breast cancer female had a long PFS by treating with the mammalian target of rapamycin inhibitor in combination with the anti‐HER‐2 agent inetetamab.

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“…Early diagnosis and treatment of breast tumors have undergone rapid progress in the recent years, and yet they remain the most frequent cancer among women and a leading cause of mortality [ 1 , 2 , 3 ]. Breast cancer is heterogeneous group of genetically predisposed diseases with diverse clinical futures [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Antitumor Effect of Iscador on Breast Cancer Cell Lines with Different Metastatic Potential

Robev

Илиев

Tsoneva

et al. 2023

IJMS

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Studies were performed for the first time on the effect of Iscador Qu and Iscador M on phototoxicity, cytotoxicity, antiproliferative activity, changes in ξ-potential of cells, membrane lipid order, actin cytoskeleton organization and migration on three breast cancer lines with different metastatic potential: MCF10A (control), MCF-7 (low metastatic) and MDA-MB231 (high metastatic) cells. The tested Iscador Qu and M did not show any phototoxicity. The antiproliferative effect of Iscador species appeared to be dose-dependent and was related to the metastatic potential of the tested cell lines. A higher selectivity index was obtained for Iscador Qu and M towards the low metastatic MCF-7 cell line compared to the high metastatic MDA-MB-231. Iscador Qu demonstrated higher selectivity for both cancer cell lines compared to Iscador M. The malignant cell lines exhibited a decrease in fibril number and thickness regardless of the type of Iscador used. The strongest effect on migration potential was observed for the low metastatic cancer cell line MCF-7 after Iscador treatment. Both Iscador species induced a slight increase in the percentage of cells in early apoptosis for the low and high metastatic cell lines, MCF-7 and MDA-MB-231, unlike control cells. Changes in the zeta potential and membrane lipid order were observed for the low metastatic MCF-7 cell line in contrast to the high metastatic MDA-MB-231 cells. The presented results reveal a higher potential of Iscador as an antitumor agent for the low metastatic cancer cell line MCF-7 compared to the high metastatic one. Iscador Qu appears to be more potent compared to Iscador M, but at this point, the exact mechanism of action is still unclear and needs further investigations.

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Developments in the Management of Metastatic HER2-Positive Breast Cancer: A Review

Cited by 15 publications

References 48 publications

Identification of biological pathways and processes regulated by NEK5 in breast epithelial cells via an integrated proteomic approach

Identification of biological pathways and processes regulated by NEK5 in breast epithelial cells via an integrated proteomic approach

Inetetamab in combination with rapamycin and chemotherapy for trastuzumab‐treated metastatic human epidermal growth factor receptor 2‐positive breast cancer with abnormal activation of PI3K/Akt/mTOR pathway

Antitumor Effect of Iscador on Breast Cancer Cell Lines with Different Metastatic Potential

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