Surgical resection of breast cancers: Molecular analysis of cancer stem cells in residual disease

Pommier, Su Ellen J.; Morgan, Rosemary E.; Limbach, Kristen E.; Jackson, Cynthia M.; Naik, Arpana; Peckham, Jennifer L.; Müller, Patrick; Condron, Mary; Jameson, Nora E.; Pommier, Rodney F.

doi:10.1016/j.surg.2019.01.001

Cited by 4 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results confirm previous work suggesting that BCSC, can be an important target and prognostic marker 41 . Previously, the lack of efficacy of NAT against the PIK3CA-defective BCSCs, one of the most commonly found genetic mutation in breast cancer, have been reported 42 . This means that NAT might select CSCs not only because of their intrinsic resistant to chemotherapy, but also because of the induction of factors that enhance tumor survival.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of chemotherapy and P2Et extract combination in ex-vivo derived tumor mammospheres from breast cancer patients

Urueña

Sandoval

Lasso

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The main cause of death by cancer is metastasis rather than local complications of primary tumors. Recent studies suggest that breast cancer stem cells (BCSCs), retains the ability to self-renew and differentiate to repopulate the entire tumor, also, they have been associated with resistance to chemotherapy and tumor recurrence, even after tumor resection. Chemotherapy has been implicated in the induction of resistant phenotypes with highly metastatic potential. Naturally occurring compounds, especially phytochemicals such as P2Et, can target different populations of cancer cells as well as BCSC, favoring the activation of immune response via immunogenic tumor death. Here, we evaluated the presence of BCSC as well as markers related to drug resistance in tumors obtained from 78 patients who had received (or not) chemotherapy before surgery. We evaluated the ex vivo response of patient tumor-derived organoids (or mammospheres) to chemotherapy alone or in combination with P2Et. A xenotransplant model engrafted with MDA-MB-468 was used to evaluate in vivo the activity of P2Et, in this model P2Et delay tumor growth. We show that patients with luminal and TNBC, and those who received neoadjuvant therapy before surgery have a higher frequency of BCSC. Further, the treatment with P2Et in mammospheres and human breast cancer cell lines improve the in vitro tumor death and decrease its viability and proliferation together with the release of immunogenic signals. P2Et could be a good co-adjuvant in antitumor therapy in patients, retarding the tumor growth by enabling the activation of the immune response.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of chemotherapy and P2Et extract combination in ex-vivo derived tumor mammospheres from breast cancer patients

Urueña

Sandoval

Lasso

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In recent years, breast cancer treatment has included surgery, chemotherapy, endocrine therapy, targeted therapy and radiotherapy. However, traditional therapies have failed to save some refractory patients [16–18]. In this context, increasing attention has been paid to the tumor microenvironment and tumor immunity [19].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic profiling of prognosis-related genes in the breast cancer immune microenvironment

Bai

Jin

Zhang

et al. 2019

Aging

View full text Add to dashboard Cite

In the microenvironment of breast cancer, immune cell infiltration is associated with an improved prognosis. To identify immune-related prognostic markers and therapeutic targets, we determined the lymphocyte-specific kinase (LCK) metagene scores of samples from breast cancer patients in The Cancer Genome Atlas. The LCK metagene score correlated highly with other immune-related scores, as well as with the clinical stage, prognosis and tumor suppressor gene mutation status (BRCA2, TP53, PTEN) of patients in the four breast cancer subtypes. A weighted gene co-expression network analysis was performed to detect representative genes from LCK metagene-related gene modules. In two of these modules, the levels of the co-expressed genes correlated highly with LCK metagene levels, so we conducted an enrichment analysis to discover their functions. We also identified differentially expressed genes in samples with high and low LCK metagene scores. By examining the overlapping results from these analyses, we obtained 115 genes, and found that 22 of them were independent predictors of overall survival in breast cancer patients. These genes were validated for their prognostic and diagnostic value with external data sets and paired tumor and non-tumor tissues. The genes identified herein could serve as diagnostic/prognostic markers and immune-related therapeutic targets in breast cancer.

show abstract

“…PIK3CA mutations are found in patients with positive lymph nodes and subsequently manifest the mutation in the BCSCs present in the residual disease. Neoadjuvant therapy does not decrease cells with PIK3CA mutations, which appear to be more resistant to chemotherapy (76). In fact, tumors in which the BCSCs present defects in the signaling pathway PI3K/Akt are more predisposed to present nodal metastases.…”

Section: Natural Products In the Control Of Bcsc And The Induction Ofmentioning

confidence: 99%

Phyto-Immunotherapy, a Complementary Therapeutic Option to Decrease Metastasis and Attack Breast Cancer Stem Cells

et al. 2020

View full text Add to dashboard Cite

In this review, we report on the complexity of breast cancer stem cells as key cells in the emergence of a chemoresistant tumor phenotype, and as a result, the appearance of distant metastasis in breast cancer patients. The search for mechanisms that increase sensitivity to chemotherapy and also allow activation of the tumor-specific immune response is of high priority. As we observed throughout this review, natural products isolated or in standardized extracts, such as P2Et or others, could act synergistically, increasing tumor sensitivity to chemotherapy, recovering the tumor microenvironment, and participating in the induction of a specific immune response. This, in turn, would lead to the destruction of cancer stem cells and the decrease in metastasis. Source of Data: Relevant studies were found using the following keywords or medical subject headings (MeSH) in PubMed, and Google Scholar: "immune response" and "polyphenols" and "natural products" and "BCSC" and "therapy" and "metabolism" and "immunogenic cell death." The focus was primarily on the most recent scientific publication.

show abstract

Surgical resection of breast cancers: Molecular analysis of cancer stem cells in residual disease

Cited by 4 publications

References 39 publications

Evaluation of chemotherapy and P2Et extract combination in ex-vivo derived tumor mammospheres from breast cancer patients

Evaluation of chemotherapy and P2Et extract combination in ex-vivo derived tumor mammospheres from breast cancer patients

Bioinformatic profiling of prognosis-related genes in the breast cancer immune microenvironment

Phyto-Immunotherapy, a Complementary Therapeutic Option to Decrease Metastasis and Attack Breast Cancer Stem Cells

Contact Info

Product

Resources

About