Vandetanib as a potential new treatment for estrogen receptor‐negative breast cancers

Hatem, Rana; Labiod, Dalila; Château-Joubert, Sophie; Plater, Ludmilla de; Botty, Rania El; Vacher, Sophie; Bonin, Florian; Servely, Jean-Luc; Dièras, Véronique; Bièche, Ivan; Marangoni, Elisabetta

doi:10.1002/ijc.29974

Cited by 36 publications

(32 citation statements)

References 30 publications

(69 reference statements)

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“…Currently, the use of targeted therapies in breast cancers is increasing, especially when conventional chemotherapy affords relatively small benefits at a cost of increased toxicity. TKIs may be a good choice because TKs are often activated and highly expressed in multiple TNBC subtypes and might be potential targets . However, most TKIs show limited efficacy against TNBC, although some have entered clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic activity of DCC‐2036, a novel tyrosine kinase inhibitor, against triple‐negative breast cancer patient‐derived xenografts by targeting AXL/MET

Shen

Zhang

Liu

et al. 2018

Intl Journal of Cancer

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Triple‐negative breast cancer (TNBC) is insensitive to endocrine therapies and targeted therapies to human epidermal growth factor receptor‐2 (HER2), estrogen receptor (ER) and progesterone receptor (PR). New targets and new targeted therapeutic drugs for TNBC are desperately needed. Our study confirmed that DCC‐2036 inhibited the proliferation, invasion, migration and epithelial‐mesenchymal transition (EMT) of TNBC cells as well as induced apoptosis. Moreover, the antiproliferative activity of DCC‐2036 was more efficient than that of most clinical drugs. In addition, the combination of DCC‐2036 and cisplatin or lapatinib had synergistic effects on TNBC cells. Mechanistically, DCC‐2036 targeted AXL/MET, especially AXL, and regulated the downstream PI3K/Akt‐NFκB signaling to exert its antitumor effect in TNBC. DCC‐2036 also inhibited the growth and metastasis of xenografted MDA‐MB‐231 cells (AXL/MET‐high TNBC cells) but not MDA‐MB‐468 cells (AXL‐low TNBC cells) in NSG mice in vivo. Furthermore, DCC‐2036 significantly inhibited tumor growth and invasion of AXL/MET‐high TNBC PDX tumors but not AXL/MET‐low TNBC PDX tumors. These results highlighted the roles of AXL/MET in cancer growth and metastasis and further verified that the critical targets of DCC‐2036 are AXL and MET, especially AXL. In addition, there was no significant toxicity of DCC‐2036 even at a high dosage. Therefore, DCC‐2036 may be a potential compound to treat TNBC, especially for tumors with AXL/MET overexpression.

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Section: Discussionmentioning

confidence: 99%

Therapeutic activity of DCC‐2036, a novel tyrosine kinase inhibitor, against triple‐negative breast cancer patient‐derived xenografts by targeting AXL/MET

Shen

Zhang

Liu

et al. 2018

Intl Journal of Cancer

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Section: Methodsmentioning

confidence: 99%

“…Their care and housing were in accordance with institutional guidelines as put forth by the French Ethical Committee, as previously detailed [44]. Sixty-seven breast cancer PDX, including 42 TNBC, 17 ER+ and 8 HER2+, were used in this study [14, 44]. They were all established from primary surgical specimens with patient informed consent, as described elsewhere [14, 44].…”

Section: Methodsmentioning

confidence: 99%

“…Sixty-seven breast cancer PDX, including 42 TNBC, 17 ER+ and 8 HER2+, were used in this study [14, 44]. They were all established from primary surgical specimens with patient informed consent, as described elsewhere [14, 44]. The ER+ PDX HBCx-3, HBCx-21, HBCx-22 and HBCx-34 have been described by Cottu et al [24, 45], HBCx-1 to HBCx-63 have been published by Marangoni et al [14], Reyal et al [25] and Hatem et al [44].…”

Section: Methodsmentioning

confidence: 99%

“…They were all established from primary surgical specimens with patient informed consent, as described elsewhere [14, 44]. The ER+ PDX HBCx-3, HBCx-21, HBCx-22 and HBCx-34 have been described by Cottu et al [24, 45], HBCx-1 to HBCx-63 have been published by Marangoni et al [14], Reyal et al [25] and Hatem et al [44]. HBCx-64 to HBCx-69, HBCx-73, HBCx-81, HBCx-86, HBCx-87, HBCx-90, HBCx-92, HBCx-95, HBCx-100, HBCx-101, HBCx-106 and HBCx-108 have not been previously published.…”

Section: Methodsmentioning

confidence: 99%

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Targeting mTOR pathway inhibits tumor growth in different molecular subtypes of triple-negative breast cancers

et al. 2016

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Triple-negative breast cancers (TNBC) are characterized by frequent alterations in the PI3K/AKT/mTOR signaling pathway. In this study, we analyzed PI3K pathway activation in 67 patient-derived xenografts (PDX) of breast cancer and investigated the anti-tumor activity of the mTOR inhibitor everolimus in 15 TNBC PDX with different expression and mutational status of PI3K pathway markers.Expression of the tumor suppressors PTEN and INPP4B was lost in 55% and 76% of TNBC PDX, respectively, while mutations in PIK3CA and AKT1 genes were rare. In 7 PDX treatment with everolimus resulted in a tumor growth inhibition higher than 50%, while 8 models were classified as low responder or resistant. Basal-like, LAR (Luminal AR), mesenchymal and HER2-enriched tumors were present in both responder and resistant groups, suggesting that tumor response to everolimus is not restricted to a specific TNBC subtype. Analysis of treated tumors showed a correlation between tumor response and post-treatment phosphorylation of AKT, increased in responder PDX, while PI3K pathway markers at baseline were not sufficient to predict everolimus response.In conclusion, targeting mTOR decreased tumor growth in 7 out of 15 TNBC PDX tested. Response to everolimus occurred in different TNBC subtypes and was associated with post-treatment increase of P-AKT.

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Ret Receptor Has Distinct Alterations and Functions in Breast Cancer

Gattelli

Hynes

Schor

et al. 2020

J Mammary Gland Biol Neoplasia

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Ret receptor tyrosine kinase is a proto-oncogene that participates in development of various cancers. Several independent studies have recently identified Ret as a key player in breast cancer. Although Ret overexpression and function have been under investigation, mainly in estrogen receptor positive breast cancer, a more comprehensive analysis of the impact of recurring Ret alterations in breast cancer is needed. This review consolidates the current knowledge of Ret alterations and their potential effects in breast cancer. We discuss and integrate data on Ret changes in different breast cancer subtypes and potential function in progression, as well as the participation of distinct Ret network signaling partners in these processes. We propose that it will be essential to define a shared molecular feature of tumors with alteration in Ret receptor, be this at the genetic level or via overexpression in order to design effective therapies to target the Ret pathway. Here we review experimental evidence from basic research and pre-clinical studies concentrating on Ret alterations as potential biomarkers for recurrence, and we discuss the possibility that targeting the Ret pathway might in the future become a treatment for breast cancer.

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Vandetanib as a potential new treatment for estrogen receptor‐negative breast cancers

Cited by 36 publications

References 30 publications

Therapeutic activity of DCC‐2036, a novel tyrosine kinase inhibitor, against triple‐negative breast cancer patient‐derived xenografts by targeting AXL/MET

Therapeutic activity of DCC‐2036, a novel tyrosine kinase inhibitor, against triple‐negative breast cancer patient‐derived xenografts by targeting AXL/MET

Targeting mTOR pathway inhibits tumor growth in different molecular subtypes of triple-negative breast cancers

Ret Receptor Has Distinct Alterations and Functions in Breast Cancer

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