Lapatinib-Based Therapy for Women With Advanced/ Metastatic Her2 Positive Breast Cancer

Zekri, Jamal; Mokhtar, Mohsen; Karim, Shanaz; Darwish, Tarek; Al‐Foheidi, Meteb; Rizvi, Azhar; S, Al-Rehaily; Mahrous, Mervat; Mansour, Mariam

doi:10.31768/2312-8852.2015.37(2):146-150

Cited by 3 publications

References 23 publications

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Cross talk between tumor stroma and cancer cells plays a critical role in progressive enrichment of cancer stem cell phenotype in primary breast tumors

Dhanota

Bal

Singh

et al. 2020

Preprint

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In order to delineate the underlying molecular mechanisms responsible for intra tumoral enrichment of BCSCs in aggressive breast tumors, firstly we evaluated the frequency and characteristics of breast cancer stem cells (BCSCs) within the tumor mass as well as in pathologically normal adjacent tissues in primary breast carcinomas of various clinical and histological grades. Then, we evaluated the expression profiles of various genes in non-cancer stem cells from these tumors to delineate the role played by cellular niche in de novo origin and/or expansion of intra-tumoral cancer stem cells.The study included primary tumor and adjacent normal breast tissue specimens from chemotherapy-naïve breast carcinoma patients. The BCSCs, identified as Lin-CD44+CD24- and aldehyde dehydrogenase 1 A1 positive were enumerated. The frequency of intra-tumoral BCSCs was correlated with various clinicopathological parameters of breast cancer. The flow-cytometrically sorted stromal cells and cancer cells from treatment naïve primary breast tumors were processed for gene expression profiling using a custom designed PCR array of genes known to facilitate cancer cell proliferation and disease progression.The frequency of BCSCs within the tumor mass as well as in the adjacent normal tissue correlated significantly with histopathological and molecular grades of tumors indicating a direct relationship of BCSC with aggressive behavior of breast cancer. A significantly higher number of BCSCs was also detected in metastatic LN group as compared to non-metastatic LN. Further, a significantly increased expression of the genes associated with growth factors, cytokines & matricellular proteins in tumors with high BCSCs content (> 5%; Hi-BCSCs tumors) as compared to Lo-BCSC tumors (with <5% intratumoral BCSC content) suggested the possible contribution of stromal cells and cancer cells in intra-tumoral expansion of CSCs. Similarly, a significant up-regulation of genes associated with hypoxia and angiogenesis in Hi-BCSCs tumors further supported the role of hypoxic environment. The expression levels of genes associated with epithelial to mesenchymal transition also followed a similar pattern. On the other hand, downregulated SNAI1 gene (generally upregulated in onset of EMT) in stromal cells of Hi-BCSCs tumors suggests a post EMT environment in Hi-BCSCs tumors.The findings suggest that the molecular crosstalk between the non-BCSC niche cells and the cancer stem cells within the breast cancer microenvironment directly contribute to formation of biologically conducive conditions for expansion of cancer stem cells.

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Cross talk between tumor stroma and cancer cells plays a critical role in progressive enrichment of cancer stem cell phenotype in primary breast tumors

Dhanota

Bal

Singh

et al. 2020

Preprint

View full text Add to dashboard Cite

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Evaluation of breast cancer stem cells in human primary breast carcinoma and their role in aggressive behavior of the disease

et al. 2021

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Targeting breast cancer stem cells by dendritic cell vaccination in humanized mice with breast tumor: preliminary results

Pham

et al. 2016

OTT

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BackgroundBreast cancer (BC) is one of the leading cancers in women. Recent progress has enabled BC to be cured with high efficiency. However, late detection or metastatic disease often renders the disease untreatable. Additionally, relapse is the main cause of death in BC patients. Breast cancer stem cells (BCSCs) are considered to cause the development of BC and are thought to be responsible for metastasis and relapse. This study aimed to target BCSCs using dendritic cells (DCs) to treat tumor-bearing humanized mice models.Materials and methodsNOD/SCID mice were used to produce the humanized mice by transplantation of human hematopoietic stem cells. Human BCSCs were injected into the mammary fat pad to produce BC humanized mice. Both hematopoietic stem cells and DCs were isolated from the human umbilical cord blood, and immature DCs were produced from cultured mononuclear cells. DCs were matured by BCSC-derived antigen incubation for 48 hours. Mature DCs were vaccinated to BC humanized mice with a dose of 106 cells/mice, and the survival percentage was monitored in both treated and untreated groups.ResultsThe results showed that DC vaccination could target BCSCs and reduce the tumor size and prolong survival.ConclusionThese results suggested that targeting BCSCs with DCs is a promising therapy for BC.

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Lapatinib-Based Therapy for Women With Advanced/ Metastatic Her2 Positive Breast Cancer

Cited by 3 publications

References 23 publications

Cross talk between tumor stroma and cancer cells plays a critical role in progressive enrichment of cancer stem cell phenotype in primary breast tumors

Cross talk between tumor stroma and cancer cells plays a critical role in progressive enrichment of cancer stem cell phenotype in primary breast tumors

Evaluation of breast cancer stem cells in human primary breast carcinoma and their role in aggressive behavior of the disease

Targeting breast cancer stem cells by dendritic cell vaccination in humanized mice with breast tumor: preliminary results

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