HMGB1 is a key factor for tamoxifen resistance and has the potential to predict the efficacy of CDK4/6 inhibitors in breast cancer

Zhang, Han; Wang, Jinlu; Li, Jingtong; Zhou, Xiaoping; Yin, Lei; Gu, Yucui; Niu, Xingjian; Yang, Yongmei; Ji, Hongfei; Zhang, Qingyuan

doi:10.1111/cas.14813

Cited by 17 publications

(21 citation statements)

References 43 publications

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“…In contrast, another study showed that miR-129-5p enhances the sensitivity of breast cancer cells to paclitaxel by inhibiting autophagy and HMGB1, thereby increasing apoptosis [ 79 ]. In addition, patients with endocrine therapy (ET)-refractory HR-positive breast cancer showed greater HMGB1 expression correlated with worse postoperative progression-free survival (PFS) [ 80 ]. Among patients with ET-resistant disease, treatment with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors benefitted the PFS of HMGB1-positive patients relative to that of HMGB1-negative patients [ 80 ].…”

Section: Roles Of Damps and Icd In The Clinical Significance Of Breast Cancermentioning

confidence: 99%

“…In addition, patients with endocrine therapy (ET)-refractory HR-positive breast cancer showed greater HMGB1 expression correlated with worse postoperative progression-free survival (PFS) [ 80 ]. Among patients with ET-resistant disease, treatment with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors benefitted the PFS of HMGB1-positive patients relative to that of HMGB1-negative patients [ 80 ]. HMGB1 promotes tamoxifen resistance via TLR4, resulting in the activation of the NF-κB signaling pathway, which is restored by CDK4/6 inhibitors [ 80 ].…”

Section: Roles Of Damps and Icd In The Clinical Significance Of Breast Cancermentioning

confidence: 99%

“…Among patients with ET-resistant disease, treatment with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors benefitted the PFS of HMGB1-positive patients relative to that of HMGB1-negative patients [ 80 ]. HMGB1 promotes tamoxifen resistance via TLR4, resulting in the activation of the NF-κB signaling pathway, which is restored by CDK4/6 inhibitors [ 80 ]. These findings suggest that HMGB1 is involved in the promotion of the ET resistance of HR-positive breast cancer.…”

Section: Roles Of Damps and Icd In The Clinical Significance Of Breast Cancermentioning

confidence: 99%

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Current and Future Therapies for Immunogenic Cell Death and Related Molecules to Potentially Cure Primary Breast Cancer

Kim¹,

Kin

2021

Cancers

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How primary breast cancer can be cured after (neo)adjuvant therapy remains unclear at the molecular level. Immune activation by anticancer agents may contribute to residual tumor cell eradication with postsurgical (neo)adjuvant chemotherapy. Chemotherapy-induced immunogenic cell death (ICD) may result in long-term immune activation with memory effector T cells, leading to a primary breast cancer cure. Anthracycline and taxane treatments cause ICD and immunogenic modulations, resulting in the activation of antitumor immunity through damage-associated molecular patterns (DAMPs), such as adenosine triphosphate, calreticulin, high mobility group box 1, heat shock proteins 70/90, and annexin A1. This response may eradicate residual tumor cells after surgical treatment. Although DAMP release is also implicated in tumor progression, metastasis, and drug resistance, thereby representing a double-edged sword, robust immune activation by anticancer agents and the subsequent acquisition of long-term antitumor immune memory can be essential components of the primary breast cancer cure. This review discusses the molecular mechanisms by which anticancer drugs induce ICD and immunogenic modifications for antitumor immunity and targeted anti-DAMP therapy. Our aim was to improve the understanding of how to eradicate residual tumor cells treated with anticancer drugs and cure primary breast cancer by enhancing antitumor immunity with immune checkpoint inhibitors and vaccines.

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Section: Roles Of Damps and Icd In The Clinical Significance Of Breast Cancermentioning

confidence: 99%

Section: Roles Of Damps and Icd In The Clinical Significance Of Breast Cancermentioning

confidence: 99%

Section: Roles Of Damps and Icd In The Clinical Significance Of Breast Cancermentioning

confidence: 99%

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Current and Future Therapies for Immunogenic Cell Death and Related Molecules to Potentially Cure Primary Breast Cancer

Kim¹,

Kin

2021

Cancers

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“…HDAC4 was also reported to promote OS cell proliferation and invasion (38). High mobility group box-1 (HMGB1) is highly expressed in a number of tumors, including lung, breast, head and neck, nasopharyngeal and colorectal cancer, indicating that it may be associated with the occurrence, invasion and metastasis of tumors (39)(40)(41)(42)(43).…”

Section: Circ-lrp6 Contributes To Osteosarcoma Progression By Regulat...mentioning

confidence: 99%

circ‑LRP6 contributes to osteosarcoma progression by regulating the miR‑141‑3p/HDAC4/HMGB1 axis

Dong

Zheng

et al. 2022

Int J Oncol

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Circular RNA-lipoprotein receptor 6 (circ-LRP6) serves a role in promoting the tumorigenesis of retinoblastoma, esophageal squamous cell cancer and oral squamous cell carcinoma; however, whether circ-LRP6 demonstrates the same effect in osteosarcoma (OS) is yet to be fully elucidated.The present study aimed to analyze the expression, role and potential molecular mechanism of circ-LRP6 in OS. The expression levels of circ-LRP6, microRNA (miR)-141-3p, histone deacetylase 4 (HDAC4) and high mobility group protein 1 (HMGB1) were evaluated by reverse transcriptionquantitative PCR in OS tissues and cell lines. Cell Counting Kit-8, Transwell and Matrigel assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Western blotting was also performed to determine HDAC4 and HMGB1 protein expression levels. Bioinformatics and dual-luciferase reporter assays were used to predict and analyze the interactions between circ-LRP6 and miR-141-3p, miR-141-3p and HDAC4, as well as between miR-141-3p and HMGB1. Additionally, RNA immunoprecipitation was performed to verify the association between circ-LRP6 and miR-141-3p. The results confirmed that circ-LRP6 was highly expressed in OS tissues and cell lines. In addition, circ-LRP6 negatively regulated the expression of miR-141-3p and, in turn, miR-141-3p negatively regulated HDAC4 and HMGB1 expression. Functional assays revealed that circ-LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells, whereas the inhibition of miR-141-3p or the overexpression of either HDAC4 or HMGB1 partly reversed the inhibitory effect of circ-LRP6 knockdown. In summary, the present study determined that circ-LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells by regulating the miR-141-3p/HDAC4/HMGB1 axis.

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“…These DAMPs induced by chemotherapeutic drugs could promote a state of anti-tumor immunity. However, other studies showed that DAMPs such as HMGB1, CRT, and ATP were also involved in BC progression, metastasis, and drug resistance ( 55 – 57 ). So, DAMPs represent a double-edged sword in BC.…”

Section: Enhancing the Antigenicity Or Adjuvanticity Of Bc Cellsmentioning

confidence: 99%

Immunostimulatory Properties of Chemotherapy in Breast Cancer: From Immunogenic Modulation Mechanisms to Clinical Practice

et al. 2022

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Breast cancer (BC) is the most common malignancy among females. Chemotherapy drugs remain the cornerstone of treatment of BC and undergo significant shifts over the past 100 years. The advent of immunotherapy presents promising opportunities and constitutes a significant complementary to existing therapeutic strategies for BC. Chemotherapy as a cytotoxic treatment that targets proliferation malignant cells has recently been shown as an effective immune-stimulus in multiple ways. Chemotherapeutic drugs can cause the release of damage-associated molecular patterns (DAMPs) from dying tumor cells, which result in long-lasting antitumor immunity by the key process of immunogenic cell death (ICD). Furthermore, Off-target effects of chemotherapy on immune cell subsets mainly involve activation of immune effector cells including natural killer (NK) cells, dendritic cells (DCs), and cytotoxic T cells, and depletion of immunosuppressive cells including Treg cells, M2 macrophages and myeloid-derived suppressor cells (MDSCs). Current mini-review summarized recent large clinical trials regarding the combination of chemotherapy and immunotherapy in BC and addressed the molecular mechanisms of immunostimulatory properties of chemotherapy in BC. The purpose of our work was to explore the immune-stimulating effects of chemotherapy at the molecular level based on the evidence from clinical trials, which might be a rationale for combinations of chemotherapy and immunotherapy in BC.

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HMGB1 is a key factor for tamoxifen resistance and has the potential to predict the efficacy of CDK4/6 inhibitors in breast cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 17 publications

References 43 publications

Current and Future Therapies for Immunogenic Cell Death and Related Molecules to Potentially Cure Primary Breast Cancer

Current and Future Therapies for Immunogenic Cell Death and Related Molecules to Potentially Cure Primary Breast Cancer

circ‑LRP6 contributes to osteosarcoma progression by regulating the miR‑141‑3p/HDAC4/HMGB1 axis

Immunostimulatory Properties of Chemotherapy in Breast Cancer: From Immunogenic Modulation Mechanisms to Clinical Practice

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