What is the best pharmacotherapeutic strategy for HER-2 positive breast cancer?

Giannone, Gaia; Milani, Andrea; Geuna, Elena; Galizia, Danilo; Biello, Federica; Montemurro, Filippo

doi:10.1080/14656566.2018.1543406

Cited by 8 publications

(5 citation statements)

References 22 publications

(1 reference statement)

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“…Breast cancer is one of the most frequent cancers and is the second leading cause of cancer death among women 1 . The human epidermal growth factor receptor-2 (HER-2), overexpressed in~20% of breast cancers 2 , predicts both reduced overall survival and shorter time to relapse in patients with breast cancer 3 . Currently, trastuzumab, a humanized monoclonal antibody targeting extracellular region of HER-2, has become the alternative choice in the treatment of HER-2-positive breast cancer 4 .…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

et al. 2020

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Trastuzumab is commonly used in the treatment of human epidermal growth factor receptor-2 positive (HER-2+) breast cancer, but its efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. In this study, publicly available expression profiling data from breast cancer and bioinformatics analyses were used to screen potential miRNAs in trastuzumab resistance. A series of gain-or loss-functional assays were performed to define the function of miR-567 and ATG5 in trastuzumab resistance and autophagy, both in vitro and in vivo. Our results showed that miR-567 was significantly decreased in trastuzumab-resistant patients compared with responding patients. Moreover, miR-567 was also downregulated in trastuzumab-resistant cells compared with parental cells. Overexpression of miR-567 reversed chemoresistance, whereas silence of miR-567 induced trastuzumab resistance, both in vitro and in vivo. In addition, enhanced miR-567 could be packaged into exosomes, incorporated into receipt cells, suppressing autophagy and reversed chemoresistance by targeting ATG5. To conclude, exosomal miR-567 plays a key role in reversing trastuzumab resistance via regulating autophagy, indicating it may be a promising therapeutic target and prognostic indicator for breast cancer patients.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

et al. 2020

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“…From publication of Emilia results, T-DM1 has been considered the preferred choice for patients progressing on trastuzumab and results superior to lapatinib and capecitabine [2,9].…”

Section: Introductionmentioning

confidence: 99%

Second line trastuzumab emtansine following horizontal dual blockade in a real-life setting

et al. 2020

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Despite relevant medical advancements, metastatic breast cancer remains an uncurable disease. HER2 signaling conditions tumor behavior and treatment strategies of HER2 expressing breast cancer. Cancer treatment guidelines uniformly identify dual blockade with pertuzumab and trastuzumab plus a taxane as best first line and trastuzumab emtansine as preferred second line choice. However, there is no prospectively designed available study focusing on the sequence and outcomes of patients treated with T-DM1 following the triplet. In the following report, data concerning a wide series of patients treated in a real-life setting are presented. Results obtained in terms of response and median progression free survival suggests a significant role for T-DM1 in disease control of metastatic HER2 expressing breast cancer.

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“…Trastuzumab (Herceptin) —The Her2-positive breast cancer subtype accounts for ~20% of all breast cancers [ 161 ], and it is associated with poor prognosis [ 162 ]. Trastuzumab is a monoclonal antibody that targets the extracellular region of HER2 serving as a targeted therapy for Her2-positive breast cancer; however, many patients develop resistance to trastuzumab following an initial response [ 163 ].…”

Section: A Multifaceted Involvement Of Autophagic Processes Modulate ...mentioning

confidence: 99%

Autophagy and Breast Cancer: Connected in Growth, Progression, and Therapy

Sharma

2023

Cells

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Despite an increase in the incidence of breast cancer worldwide, overall prognosis has been consistently improving owing to the development of multiple targeted therapies and novel combination regimens including endocrine therapies, aromatase inhibitors, Her2-targeted therapies, and cdk4/6 inhibitors. Immunotherapy is also being actively examined for some breast cancer subtypes. This overall positive outlook is marred by the development of resistance or reduced efficacy of the drug combinations, but the underlying mechanisms are somewhat unclear. It is interesting to note that cancer cells quickly adapt and evade most therapies by activating autophagy, a catabolic process designed to recycle damaged cellular components and provide energy. In this review, we discuss the role of autophagy and autophagy-associated proteins in breast cancer growth, drug sensitivity, tumor dormancy, stemness, and recurrence. We further explore how autophagy intersects and reduces the efficacy of endocrine therapies, targeted therapies, radiotherapy, chemotherapies as well as immunotherapy via modulating various intermediate proteins, miRs, and lncRNAs. Lastly, the potential application of autophagy inhibitors and bioactive molecules to improve the anticancer effects of drugs by circumventing the cytoprotective autophagy is discussed.

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What is the best pharmacotherapeutic strategy for HER-2 positive breast cancer?

Cited by 8 publications

References 22 publications

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

Second line trastuzumab emtansine following horizontal dual blockade in a real-life setting

Autophagy and Breast Cancer: Connected in Growth, Progression, and Therapy

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