A review of current progress in triple-negative breast cancer therapy

Shen, Meiying; Pan, Huawen; Chen, Yuxia; Xu, Yu; Yang, Weixiong; Wu, Zeyan

doi:10.1515/med-2020-0138

Cited by 58 publications

(44 citation statements)

References 43 publications

(42 reference statements)

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“…These immune cells were mainly present in IS3 with the best tumor prognosis, we also observed that 47 immune checkpoint-related genes were significantly different in the two cohorts and were responsible for maintaining autoimmune tolerance and regulating the persistence and intensity of the immune response. Interestingly, the suppression of immune checkpoint genes has been confirmed to reverse the inhibition of the TIME on tumor immunity and accelerate the apoptosis of tumor cells, which is a potential new possibility for future treatment of TNBC ( Shen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…According to the expression of estrogen receptors (ER), progesterone receptors (PGR), and human epidermal growth factor receptor 2 (HER2), three subtypes are commonly used for breast cancer clinical classification: the ER/PGR-positive subtype, the HER2-positive subtype, and TNBC, with the most aggressive behavior. TNBC accounts for nearly 15% of BC patients annually, and it is characterized by a high metastasis/recurrence rate and a short survival time ( Shen et al, 2020 ). Approximately 50% of TNBC patients who undergo radical surgery without metastasis will develop a disease recurrence ( Liedtke et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

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Immune Classification and Immune Landscape Analysis of Triple-Negative Breast Cancer

Jiao

et al. 2021

Front. Genet.

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Background: To classify triple-negative breast cancer (TNBC) immunotyping using the public database, analyze the differences between subtypes in terms of clinical characteristics and explore the role and clinical significance of immune subtypes in TNBC immunotherapy.Methods: We downloaded TNBC data from the cBioPortal and GEO databases. The immune genes were grouped to obtain immune gene modules and annotate their biological functions. Log-rank tests and Cox regression were used to evaluate the prognosis of immune subtypes (IS). Drug sensitivity analysis was also performed for the differences among immune subtypes in immunotherapy and chemotherapy. In addition, dimension reduction analysis based on graph learning was utilized to reveal the internal structure of the immune system and visualize the distribution of patients.Results: Significant differences in prognosis were observed between subtypes (IS1, IS2, and IS3), with the best in IS3 and the worst in IS1. The sensitivity of IS3 to immunotherapy and chemotherapy was better than the other two subtypes. In addition, Immune landscape analysis found the intra-class heterogeneity of immune subtypes and further classified IS3 subtypes (IS3A and IS3B). Immune-related genes were divided into seven functional modules (The turquoise module has the worst prognosis). Five hub genes (RASSF5, CD8A, ICOS, IRF8, and CD247) were screened out as the final characteristic genes related to poor prognosis by low expression.Conclusions: The immune subtypes of TNBC were significantly different in prognosis, gene mutation, immune infiltration, drug sensitivity, and heterogeneity. We validated the independent role of immune subtypes in tumor progression and immunotherapy for TNBC. This study provides a new perspective for personalized immunotherapy and the prognosis evaluation of TNBC patients in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune Classification and Immune Landscape Analysis of Triple-Negative Breast Cancer

Jiao

et al. 2021

Front. Genet.

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“…Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) and is highly metastatic and lethal [1,2]. Although substantial efforts have gone into identifying treatments for TNBC in recent decades, the median survival time of TNBC patients is still less than 15 months largely due to the absence of effective drugs in the clinic [3,4]. Since its discovery, TNBC has been a challenge in the cancer treatment eld [3][4][5], warranting the discovery of novel, potent therapeutics against TNBC.…”

Section: Introductionmentioning

confidence: 99%

“…Although substantial efforts have gone into identifying treatments for TNBC in recent decades, the median survival time of TNBC patients is still less than 15 months largely due to the absence of effective drugs in the clinic [3,4]. Since its discovery, TNBC has been a challenge in the cancer treatment eld [3][4][5], warranting the discovery of novel, potent therapeutics against TNBC.…”

Section: Introductionmentioning

confidence: 99%

Triptonide Effectively Inhibits Triple-Negative Breast Cancer Metastasis Through Concurrent Degradation Of Twist1 And Notch1 Oncoproteins

Zhang

Meng

Liu

et al. 2021

Preprint

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Background: Triple-negative breast cancer (TNBC) is highly metastatic and lethal. Due to a lack of druggable targets for this disease, there are no effective therapies in the clinic.Methods: We explored the ability of active compounds derived from natural herbs to inhibit TNBC metastasis using the methods of molecular biology, cell biology, protein chemistry, pharmacology, and xenografted mice.Results: Here, we showed that triptonide, a small molecule from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F, potently inhibited TNBC cell migration, invasion, and vasculogenic mimicry, and effectively suppressed TNBC tumor growth and lung metastasis in xenografted mice with no observable toxicity. Molecular mechanistic studies revealed that triptonide strongly triggered the degradation of master epithelial-mesenchymal transition (EMT)-inducing protein Twist1 through the lysosomal system and reduced Notch1 expression and NF-κB phosphorylation, which consequently diminished the expression of pro-metastatic and angiogenic genes N-cadherin, VE-cadherin, and vascular endothelial cell growth factor receptor 2 (VEGFR2).Conclusions: Triptonide effectively suppressed TNBC cell tumorigenesis, vasculogenic mimicry, and strongly inhibited the metastasis of TNBC via degradation of Twist1 and Notch1 oncoproteins, downregulation of metastatic and angiogenic gene expression, and reduction of NF-κB signaling pathway. Our findings provide a new strategy for treating highly lethal TNBC and offer a potential new drug candidate for combatting this aggressive disease.

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“…About 15% of BC cases are triple-negative breast cancers (TNBCs), lacking the expression of ERα, PR and HER2-amplification and are thus not responsive to targeted therapies against ERα or HER2. These cancers are associated with a poorer prognosis due to a higher rate of metastatic progression and resistance to treatment (16,17). Notably, TNBC may be responsive to estrogen stimulation via ERα-independent pathways, promoting tumor formation and progression via different molecular mechanisms (18).…”

Section: Introductionmentioning

confidence: 99%

ERα-LBD, a novel isoform of estrogen receptor alpha, promotes breast cancer proliferation and endocrine resistance

Strillacci

Sansone

Rajasekhar

et al. 2021

Preprint

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Estrogen receptor alpha (ERα) drives mammary gland development and breast cancer (BC) growth through an evolutionarily conserved linkage of DNA binding and hormone activation functions. Therapeutic targeting of the hormone binding pocket is a widely utilized and successful strategy for breast cancer prevention and treatment. However, resistance to this endocrine therapy is frequently encountered and may occur through bypass or reactivation of ER-regulated transcriptional programs. We now identify the induction of a novel ERα isoform, ERα-LBD, that is encoded by an alternative ESR1 transcript and lacks the activation function and DNA binding domains. Despite lacking the transcriptional activity, ERα-LBD is found to promote breast cancer growth and resistance to the ERα antagonist fulvestrant. ERα-LBD is predominantly localized to the cytoplasm and mitochondria of BC cells and leads to enhanced glycolysis, respiration and stem-like features. Intriguingly, ERα-LBD expression and function does not appear to be restricted to cancers that express full length ERα but also promotes growth of triple negative breast cancers and ERα-LBD transcript (ESR1-LBD) is also present in BC samples from both ERα(+) and ERα(-) human tumors. These findings point to ERα-LBD as a potential mediator of breast cancer progression and therapy resistance.

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A review of current progress in triple-negative breast cancer therapy

Cited by 58 publications

References 43 publications

Immune Classification and Immune Landscape Analysis of Triple-Negative Breast Cancer

Immune Classification and Immune Landscape Analysis of Triple-Negative Breast Cancer

Triptonide Effectively Inhibits Triple-Negative Breast Cancer Metastasis Through Concurrent Degradation Of Twist1 And Notch1 Oncoproteins

ERα-LBD, a novel isoform of estrogen receptor alpha, promotes breast cancer proliferation and endocrine resistance

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