Article
Oncology
Guilherme Nader-Marta, Veronique Debien, Daniel Eiger, Zoi Tsourti, Rafael Caparica, Marie Kassapian, Sylvia Napoleone, Susanne Hultsch, Larissa Korde, Yingbo Wang, Saranya Chumsri, Kathleen Pritchard, Michael Untch, Meritxell Bellet-Ezquerra, Daniela Dornelles Rosa, Alvaro Moreno-Aspitia, Martine Piccart, Urania Dafni, Evandro de Azambuja
Summary: The sub-analysis of the ALTTO trial demonstrates that patients with small node-negative breast cancer treated with trastuzumab and concomitant chemotherapy have excellent long-term outcomes.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Ana Carla Castro-Guijarro, Angel Matias Sanchez, Marina Ines Flamini, Christoph F. A. Vogel
Summary: This study aims to identify biomarkers for predicting disease progression and therapy efficacy in HER2-positive breast cancer, as well as to overcome resistance. Combining anti-HER2 therapies shows potential in inhibiting cell adhesion and migration critical for cancer metastasis. Deregulated proteins in resistant cells may serve as potential biomarkers of therapy response and resistance. These findings are promising for personalized breast cancer management to maximize the safety and efficacy of anti-HER2 therapies.
Article
Immunology
Sofia Batalha, Catarina Monteiro Gomes, Catarina Brito
Summary: This study presents a unique human 3D model for studying the immune effects of anti-HER2 biologicals, which can be used to test novel therapy regimens and improve anti-tumor immune function.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Mark M. Moasser
Summary: The pharmaceutical inactivation of driver oncogenes has revolutionized cancer treatment, but challenges remain for HER2-amplified cancers. The monotherapy activities associated with HER2-targeting therapies are not as effective as for other oncogene-driven cancers. Further research is needed to understand the mechanism of HER2 inactivation for treatment.
Article
Oncology
Fangfang Duan, Muyi Zhong, Yuyu Ma, Chenge Song, Lehong Zhang, Ying Lin, Zhiyong Wu, Yuanqi Zhang, Jiajia Huang, Fei Xu, Yanxia Shi, Shusen Wang, Zhongyu Yuan, Wen Xia, Xiwen Bi
Summary: The switching mode showed superior efficacy compared to continuing mode in subsequent anti-HER2 therapy for patients with HER2-positive refractory metastatic breast cancer.
Review
Oncology
Caroline Fong, Ian Chau
Summary: This paper summarizes the evidence supporting HER2 targeting in stomach cancers, reviews mechanisms of drug resistance, and outlines new treatment approaches that may change the way we treat this disease.
Article
Oncology
Mei-Hua Jin, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
Summary: This study revealed higher PD-L1 expression in trastuzumab-resistant HER2-positive cancer cells and showed that blocking PD-L1 could reverse resistance to trastuzumab. Co-targeting HER2 and WEE1 was found to overcome resistance to trastuzumab in HER2-positive cancers, offering potential therapeutic options for patients.
Article
Chemistry, Medicinal
Jingru Qiu, Qinghong Liu, Peixia Li, Qiaoyun Jiang, Weijia Chen, Donghai Li, Guiling Li, Gang Shan
Summary: This work presents a photocatalytic approach called ligand-directed photodegradation of interacting proteins (LDPIP) for efficient degradation of protein-protein heterodimers. LDPIP utilizes a photosensitizing protein ligand, appropriate light, and molecular oxygen to induce oxidative damage to both the ligand-binding protein and its interacting protein partner. As a showcase study, a photosensitizing HER2 ligand HER-PS-I was designed based on the FDA-approved HER2 inhibitor lapatinib to degrade HER2 and its difficult-to-target interacting protein partner HER3. HER-PS-I exhibited excellent anticancer activity in drug-resistant MDA-MB-453 cells and multicellular spheroids. The LDPIP approach holds promise for degrading undruggable or difficult-to-drug proteins.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Samar Alanazi, Wasim Feroz, Rosalin J. Mishra, Mary Kate T. Kilroy, Hima Patel, Long Yuan, Sarah Storr, Joan Garrett
Summary: HER2 is over-expressed in 15% to 20% of breast cancers and HER3 plays a critical role in HER2 mediated tumorigenesis. In this study, proteins that bound to HER3 when the HER family was inhibited by the pan-HER inhibitor neratinib were identified. Non-muscle myosin IIA (NMIIA) was found to increase upon neratinib treatment and its loss reduces HER2+ breast cancer growth. This study highlights the importance of HER3 and NMIIA in HER2+ breast cancer progression.
Article
Oncology
Valentina Guarneri, Maria V. Dieci, Gaia Griguolo, Federica Miglietta, Fabio Girardi, Giancarlo Bisagni, Daniele G. Generali, Katia Cagossi, Samanta Sarti, Antonio Frassoldati, Lorenzo Gianni, Luigi Cavanna, Graziella Pinotti, Antonino Musolino, Federico Piacentini, Saverio Cinieri, Aleix Prat, PierFranco Conte
Summary: The Cher-LOB study demonstrated that the combination of lapatinib-trastuzumab plus chemotherapy is more effective in increasing pCR rate compared to other treatment options. The analysis confirmed the prognostic role of pCR and TILs, showing a potential for better outcomes with the lapatinib-trastuzumab combination. Luminal-A subtype was identified as a significant predictor for improved RFS.
EUROPEAN JOURNAL OF CANCER
(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
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.
Article
Biochemistry & Molecular Biology
Jiangwei Ni, Kun Chen, Jiandong Zhang, Xiang Zhang
Summary: This study explored the role of GPX4 and mTOR in regulating the response of lung cancer cells to Lapatinib. The upregulation of GPX4 in Lap resistant NSCLC cells was found to be due to enhanced activation of mTORC1. Inhibition of mTORC1 led to downregulation of GPX4, which promoted Lap induced ferroptosis. These findings suggest that targeting GPX4 might enhance the antitumor effects of Lap.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Priya Rastogi, Gong Tang, Saima Hassan, Charles E. Geyer Jr, Catherine A. Azar, Gustav C. Magrinat, J. Marie Suga, Harry D. Bear, Luis Baez-Diaz, Shakir Sarwar, Jean-Francois Boileau, Adam M. Brufsky, Henry R. Shibata, Hanna Bandos, Soonmyung Paik, Greg Yothers, Sandra M. Swain, Eleftherios P. Mamounas, Norman Wolmark
Summary: This study aimed to compare the efficacy of trastuzumab alone or in combination with lapatinib in treating HER2-positive breast cancer patients. The results showed that although the combination therapy and the use of lapatinib had better outcomes, the differences were not statistically significant. However, achieving pathological complete response correlated with improved prognosis, especially in the ER-negative subset.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Review
Multidisciplinary Sciences
Ye Yuan, Xumei Liu, Yi Cai, Wenyuan Li
Summary: According to this study, pyrotinib combined with chemotherapy is more effective than lapatinib combined with chemotherapy in terms of PFS and ORR for patients with HER2-positive metastatic breast cancer, but it carries higher safety risks.
