Review
Oncology
G. Nader-Marta, D. Martins-Branco, E. de Azambuja
Summary: HER2-positive breast cancer is a subtype of breast malignancy with aggressive behavior and high recurrence rates. The combination of trastuzumab, pertuzumab, and a taxane remains the preferred first-line therapy. Recent studies have shown that trastuzumab deruxtecan is more effective than trastuzumab emtansine as a second-line treatment. Other treatment options include T-DM1, tucatinib, trastuzumab, and capecitabine, as well as trastuzumab with different chemotherapy partners.
Article
Medicine, Research & Experimental
Myrto Moutafi, Charles J. Robbins, Vesal Yaghoobi, Aileen Fernandez, Sandra Martinez-Morilla, Vasiliki Xirou, Yalai Bai, Yan Song, Patricia Gaule, Joseph Krueger, Kenneth Bloom, Salisha Hill, Daniel C. Liebler, Regan Fulton, David L. Rimm
Summary: The efficacy of the antibody drug conjugate Trastuzumab deruxtecan (T-DXd) in HER2 low breast cancer patients suggests the need for revision of the conventional HER2 assays. In this study, an optimized dynamic range for unamplified HER2 detection in breast cancer was determined and a quantitative assay to stratify HER2 expression in unamplified cases was designed. The application of this assay to a large number of breast cancer cases demonstrated its potential for selecting optimal patients for T-DXd treatment.
LABORATORY INVESTIGATION
(2022)
Article
Clinical Neurology
Jiaxu Wang, Meng Li, Jing Zhang, Qing Gao, Zhaoxi Ding, Jinhao Sun
Summary: The aim of this animal study was to investigate the mechanisms underlying the efficacy of paliperidone, an antipsychotic drug approved by the US FDA for the treatment of schizophrenia. The results showed that paliperidone alleviated neuronal damage induced by MK-801 through the PP2A/PTEN pathway.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Oncology
Chenchen Ji, Feng Li, Yang Yuan, Huiqiang Zhang, Li Bian, Shaohua Zhang, Tao Wang, Jianbin Li, Zefei Jiang
Summary: This study compared the efficacy and safety between novel anti-human epidermal growth factor receptor 2 antibody-drug conjugates (ADCs) and trastuzumab emtansine for patients with tyrosine kinase inhibitor (TKI) treatment failure. The results showed that both T-Dxd and other novel anti-HER2 ADCs had significantly better progression-free survival and objective response rate than T-DM1, with tolerable toxicities.
Article
Medicine, Research & Experimental
Jinping Li, Yaobang Liu, Bing Lian, Hong Li, Dahai Chai, Yali Gao, Yanbai Wang
Summary: This study found that histidine triad nucleotide-binding protein 3 (HINT3) is decreased in breast cancer tissues. In vitro experiments showed that HINT3 knockdown promoted the proliferation and migration of breast cancer cells, while overexpression inhibited these processes. Additionally, HINT3 inhibited breast cancer cell signaling pathway activation by upregulating phosphatase and tensin homolog (PTEN). These findings demonstrate the inhibitory role of HINT3 in the proliferation, migration, and tumor development of breast cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2023)
Editorial Material
Oncology
Alicia F. C. Okines, Nicholas C. Turner
Summary: HER2 amplification heterogeneity is linked to resistance to trastuzumab emtansine in the neoadjuvant setting, highlighting the significance of determining whether varying HER2-positive cancer types require distinct treatment approaches.
Review
Oncology
Kreina Sharela Vega Cano, David Humberto Marmolejo Castaneda, Santiago Escriva-de-Romani, Cristina Saura
Summary: Therapeutic advances have significantly improved the natural history of HER2-positive metastatic breast cancer. Double anti-HER2 blockade with a taxane is currently the best option in first-line, but T-DXd has emerged as the new standard in second-line. New treatments and combinations are being developed to address resistance and progress in these patients.
Article
Biochemistry & Molecular Biology
Rong Liu, Guangxi Yang, Min Bao, Zhongmei Zhou, Xiaoyun Mao, Wenjing Liu, Xiaoyan Jiang, Di Zhu, Xinle Ren, Jian Huang, Ceshi Chen
Summary: This study identifies STAMBPL1 as a deubiquitinase of MKP-1 in breast cancer cells, which stabilizes MKP-1 protein by deubiquitination. Depletion of STAMBPL1 and MKP-1 increases breast cancer sensitivity to cisplatin and activates the JNK signaling pathway. These findings suggest that the STAMBPL1/MKP-1 axis could be a potential therapeutic target in breast cancer.
Review
Oncology
Daniel Eiger, Elisa Agostinetto, Rita Saude-Conde, Evandro de Azambuja
Summary: The article discusses the expression of HER2 in breast cancer and the development of drugs targeting HER2. Patients with HER2-positive breast cancer have higher chances of cure and survival, and now there are also treatments available for patients with lower levels of HER2 expression.
Article
Medicine, Research & Experimental
Gefei Wu, Jiasheng Hu, Hongmin Zhu, Shuhua Wu, Sheng Huang, Zhisheng Liu
Summary: The study demonstrated the therapeutic effect of melatonin (MT) on febrile convulsion (FC) by modulating the MEG3/miR-223/PTEN/AKT pathway, suggesting MT as a novel strategy for FC treatment.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Article
Oncology
Sanja Loeb, Eva Linsmeier, Saskia-Laureen Herbert, Tanja Schlaiss, Matthias Kiesel, Joerg Wischhusen, Jessica Salmen, Peter Kranke, Anne Quenzer, Florian Kurz, Claire Weiss, Elena Gerhard-Hartmann, Achim Woeckel, Joachim Diessner
Summary: The purpose of this study was to investigate the changes in HER2 subtypes between primary breast cancer and recurrent disease. The results showed that HER2 expression increased during the progression of the disease. This information is important for the development of therapeutic options for breast cancer patients.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Colin Carlock, Yunpeng Bai, Allison Paige-Hood, Qinglin Li, Frederick Nguele Meke, Zhong-Yin Zhang
Summary: Overexpression of PRL2 and reduced PTEN protein are frequently observed in patients with acute myeloid leukemia (AML). Inhibiting PRL2 can prolong animal survival and slow the accumulation of leukemia blasts in the bone marrow niche. This study provides evidence for the viability of PRL2 inhibition as a therapeutic strategy for improving clinical outcomes in AML and other PTEN-deficient cancers.
Article
Medicine, Research & Experimental
Cancan Lyu, Yuanchao Ye, Maddison M. Lensing, Kay-Uwe Wagner, Ronald J. Weigel, Songhai Chen
Summary: In HER2(+) breast cancer, overactivation of HER2 leads to aberrant G(i/o)-GPCR signaling, promoting cancer progression and resistance to HER2-targeted therapy. Pharmacologically deactivating GPCR signaling can block tumor growth and enhance therapeutic efficacy.
Editorial Material
Medicine, General & Internal
Ron Bose, Cynthia X. Ma
Summary: A recent study suggests that HER2-mutated breast cancer may develop resistance to drugs that inhibit the tyrosine kinase domain of HER2 through developing mutations in HER3, which enhance the dimerization between HER2 and HER3. The HER3 mutations augment signaling. This study supports a specific approach to overcoming mutant-HER3-mediated resistance.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Oncology
Chewei Anderson Chang, Jayu Jen, Shaowen Jiang, Azin Sayad, Arvind Singh Mer, Kevin R. Brown, Allison M. L. Nixon, Avantika Dhabaria, Kwan Ho Tang, David Venet, Christos Sotiriou, Jiehui Deng, Kwok-Kin Wong, Sylvia Adams, Peter Meyn, Adriana Heguy, Jane A. Skok, Aristotelis Tsirigos, Beatrix Ueberheide, Jason Moffat, Abhyudai Singh, Benjamin Haibe-Kains, Alireza Khodadadi-Jamayran, Benjamin G. Neel
Summary: Resistance to targeted therapies in HER2-positive breast cancer is often attributed to the presence of drug-tolerant persisters (DTPs). This study reveals that HER2 TKI treatment leads to the emergence of DTPs with different transcriptomes, and these DTPs are originated from pre-DTP cells that cycle stochastically. The findings provide insights into the ontogeny of DTPs and potential vulnerabilities for therapeutic targeting.