From molecular insight to therapeutic strategy: The holistic approach for treating triple negative breast cancer

Bhattacharya, R.K.; Banerjee, K.; Mukherjee, Nupur; Sen, M.; Mukhopadhyay, Ashis

doi:10.1016/j.prp.2017.01.001

Cited by 10 publications

(9 citation statements)

References 35 publications

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“…TNBC accounts for approximately 20% of all breast cancers [1, 2]. So far, no molecularly targeted therapy has been FDA-approved to treat patients with TNBC primarily due to lack of validated therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

“…Breast tumor subtypes are defined based on the expression of three primary identifiers: estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Breast tumors lacking all three markers are referred to as triple-negative breast cancer (TNBC), which account for 15–20% of all breast cancer cases [1, 2]. Treatment options for patients with TNBC are currently limited to the combinations of conventional chemotherapy in both primary and metastatic setting, radiation, and surgery in early disease [1, 2].…”

Section: Introductionmentioning

confidence: 99%

“…Breast tumors lacking all three markers are referred to as triple-negative breast cancer (TNBC), which account for 15–20% of all breast cancer cases [1, 2]. Treatment options for patients with TNBC are currently limited to the combinations of conventional chemotherapy in both primary and metastatic setting, radiation, and surgery in early disease [1, 2]. TNBC frequently develops early recurrence after initial treatment and displays a tendency to metastasize primarily to visceral sites such as the lung, liver and brain resulting in significantly reduced overall survival [3, 4].…”

Section: Introductionmentioning

confidence: 99%

“…The CD44 high /CD24 low population has been shown to have an increased ability to undergo epithelial-mesenchymal transition, thereby rendering tumor cells more motile and migratory, which is critical to the initiation of breast cancer metastasis [13]. Metastatic TNBC is currently considered incurable [1, 5, 6], underscoring the need for new therapeutic strategies. Data from patient-derived tumor xenograft (PDX) models have suggested important roles for CDKs in the metastatic phenotype and in preclinical studies the pan-CDK inhibitor dinaciclib demonstrated antineoplastic activity [14].…”

Section: Introductionmentioning

confidence: 99%

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Antineoplastic effects of selective CDK9 inhibition with atuveciclib on cancer stem-like cells in triple-negative breast cancer

et al. 2018

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Treatment options for triple-negative breast cancer (TNBC) are limited due to the lack of efficient targeted therapies, frequently resulting in recurrence and metastatic disease. Accumulating evidence suggests that a small population of cancer stem-like cells (CSLCs) is responsible for tumor recurrence and therapy resistance. Here we investigated the role of cyclin-dependent kinase 9 (CDK9) in TNBC. Using The Cancer Genome Atlas (TCGA) data we found high-CDK9 expression correlates with worse overall survival in TNBC patients. Pharmacologic inhibition of CDK9 with atuveciclib in high-CDK9 expressing TNBC cell lines reduced expression of CDK9 targets MYC and MCL1 and decreased cell proliferation and survival. Importantly, atuveciclib inhibited the growth of mammospheres and reduced the percentage of CD24low/CD44high cells, indicating disruption of breast CSLCs (BCSLCs). Furthermore, atuveciclib impaired 3D invasion of tumorspheres suggesting inhibition of both invasion and metastatic potential. Finally, atuveciclib enhanced the antineoplastic effects of Cisplatin and promoted inhibitory effects on BCSLCs grown as mammospheres. Together, these findings suggest CDK9 as a potential therapeutic target in aggressive forms of CDK9-high TNBC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antineoplastic effects of selective CDK9 inhibition with atuveciclib on cancer stem-like cells in triple-negative breast cancer

et al. 2018

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“…Most basal‐like breast tumors lack expression of ER, PR, and HER2 and are referred to as triple‐negative breast cancer (TNBC) . TNBC is highly metastatic and currently there are no molecular‐based targeted therapies to treat the disease .…”

Section: Introductionmentioning

confidence: 99%

Racial disparities in survival outcomes by breast tumor subtype among African American women in Memphis, Tennessee

et al. 2017

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Racial disparities in survival among African American (AA) women in the United States have been well documented. Breast cancer mortality rates among AA women is higher in Memphis, Tennessee as compared to 49 of the largest US cities. In this study, we investigated the extent to which racial/ethnic disparities in survival outcomes among Memphis women are attributed to differences in breast tumor subtype and treatment outcomes. A total of 3527 patients diagnosed with stage I–IV breast cancer between January 2002 and April 2015 at Methodist Health hospitals and West Cancer Center in Memphis, TN were included in the analysis. Kaplan–Meier survival curves were generated and Cox proportional hazards regression were used to compare survival outcomes among 1342 (38.0%) AA and 2185 (62.0%) non‐Hispanic White breast cancer patients by race and breast tumor subtype. Over a mean follow‐up time of 29.9 months, AA women displayed increased mortality risk [adjusted hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.35–2.03] and were more likely to be diagnosed at advanced stages of disease. AA women with triple‐negative breast cancer (TNBC) had the highest death rate at 26.7% compared to non‐Hispanic White women at 16.5%. AA women with TNBC and luminal B/HER2‐ breast tumors had the highest risk of mortality. Regardless of race, patients who did not have surgery had over five times higher risk of dying compared to those who had surgery. These findings provide additional evidence of the breast cancer disparity gap between AA and non‐Hispanic White women and highlight the need for targeted interventions and policies to eliminate breast cancer disparities in AA populations, particularly in Memphis, TN.

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E-jet 3D printed drug delivery implants to inhibit growth and metastasis of orthotopic breast cancer

et al. 2020

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From molecular insight to therapeutic strategy: The holistic approach for treating triple negative breast cancer

Cited by 10 publications

References 35 publications

Antineoplastic effects of selective CDK9 inhibition with atuveciclib on cancer stem-like cells in triple-negative breast cancer

Antineoplastic effects of selective CDK9 inhibition with atuveciclib on cancer stem-like cells in triple-negative breast cancer

Racial disparities in survival outcomes by breast tumor subtype among African American women in Memphis, Tennessee

E-jet 3D printed drug delivery implants to inhibit growth and metastasis of orthotopic breast cancer

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