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Journal articles on the topic 'He53'

Author: Grafiati

Published: 25 July 2024

Last updated: 31 July 2025

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1

Kent, Matthew R., Delia Calderon, Katherine M. Silvius, et al. "Abstract 3533: Zebrafish her3 knockout impacts developmental and rhabdomyosarcoma-related gene signatures." Cancer Research 83, no. 7_Supplement (2023): 3533. http://dx.doi.org/10.1158/1538-7445.am2023-3533.

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Abstract HES3 is a basic helix-loop-helix transcription factor that regulates neural stem cell renewal during development. HES3 overexpression is predictive of reduced overall survival in patients with fusion-positive rhabdomyosarcoma, a pediatric cancer that resembles immature and undifferentiated skeletal muscle and is most commonly driven by the fusion-oncogene PAX3-FOXO1. However, the mechanisms of HES3 cooperation in PAX3-FOXO1 driven rhabdomyosarcoma are unclear and are likely related to her3/HES3’s role in neurogenesis. To investigate HES3’s function during development, we generated a z

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Santana, Ana Flávia Mendonça, André Luís Teixeira Fernandes, Everaldo Miranda, Leonardo Otávio Coronado, Lourena Rios Tibery, and José Roberto Delalibera Finzer. "HOPS: The Aromatic Ingredient of Breweries." Revista de Gestão Social e Ambiental 18, no. 9 (2024): e08463. http://dx.doi.org/10.24857/rgsa.v18n9-200.

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Objective: The main objective of this study is to produce and characterize the raw material used to manufacture beer, including planting and harvesting by one of the largest brewing groups in the country, the Petropólis group, with a unit installed in the city of Uberaba/MG with a built area of 108,000 m². Theoretical Framework: Most hops used for brewing in Brazil are imported from countries such as Germany and the United States. However, certain varieties have adapted to the Brazilian climate and achieved significant yields and qualities. Method: Hop samples were collected in the city of Ube

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Beckford Vera, Denis, Jason Li, Le-Cun Xu, et al. "Preclinical evaluation of novel HER3-targeting radioconjugates for the imaging and treatment of HER3-expressing cancers." Journal of Clinical Oncology 41, no. 16_suppl (2023): e15114-e15114. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e15114.

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e15114 Background: HER3 overexpression in tumors is associated with poor survival and is implicated in drug resistance mechanisms of HER1 (EGFR) and HER2 targeted therapies. Although antibodies against HER3 have been developed and evaluated in clinical trials, no HER3 targeted therapy has been approved, underscoring the unmet need for novel HER3 therapeutic approaches. We hypothesized that HER3 radioligand targeted therapies could provide enhanced therapeutic efficacy against HER3-positive cancers through the energy deposited by alpha or beta emitting radionuclides in tumor cells. Here we desc

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Koyama, Kumiko, Hirokazu Ishikawa, Manabu Abe, et al. "Patritumab deruxtecan (HER3-DXd), a novel HER3 directed antibody drug conjugate, exhibits in vitro activity against breast cancer cells expressing HER3 mutations with and without HER2 overexpression." PLOS ONE 17, no. 5 (2022): e0267027. http://dx.doi.org/10.1371/journal.pone.0267027.

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ErbB3 (HER3), a member of the HER family, is overexpressed in various cancers and plays an important role in cell proliferation and survival. Certain HER3 mutations have also been identified as oncogenic drivers, making them potential therapeutic targets. In the current study, antitumor activity of patritumab deruxtecan (HER3-DXd), a HER3 directed antibody drug conjugate, was evaluated in tumor models with clinically reported HER3 mutations. MDA-MB-231, a HER3-negative human triple-negative breast cancer cell line, was transduced with lentiviral vectors encoding HER3 wild type (HER3WT), one of

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Komatsu, Nagiho, Saori Sato, Sumie Muramatsu, Ryuichi Nakamura, and Kumiko Koyama. "Abstract 3996: The impact of HER3 dynamics on the efficacy of HER3-DXd, a novel HER3 directed antibody-drug conjugate." Cancer Research 83, no. 7_Supplement (2023): 3996. http://dx.doi.org/10.1158/1538-7445.am2023-3996.

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Abstract Background: HER3 is broadly expressed in various solid tumor types, and its expression can be upregulated by treatment with receptor tyrosine kinase inhibitors (RTKi) such as EGFR TKIs used to treat EGFR-mutated NSCLC. HER3-DXd, a novel antibody-drug conjugate (ADC) composed of a human anti-HER3 IgG1 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload (DXd), is currently being studied in clinical trials for breast cancer and NSCLC. As previously reported, HER3-DXd treatment transiently decreases HER3 expression levels in tumors and EGFR TKIs incre

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O'Hare, Thomas, Jaclyn Cleveland, Valerie M. Jansen, and David Dornan. "Abstract 3121: Therapeutic potential of a HER3 antibody-drug conjugate for the treatment of HER3-expressing cancers." Cancer Research 84, no. 6_Supplement (2024): 3121. http://dx.doi.org/10.1158/1538-7445.am2024-3121.

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Abstract To address the need for targeted therapy in the treatment of HER3-positive solid tumors, the human HER3 mAb, seribantumab, was evaluated in the context of an antibody-drug conjugate (ADC). As a proof-of-concept, seribantumab was conjugated with a cleavable valine-citrulline linker and monomethyl auristatin E (MMAE) payload via the stochastic cysteine conjugation method to yield HER3-ADC1. A drug-antibody ratio of 4 was selected for preclinical assessment in HER3-expressing models. Methods: HER3-ADC1 was evaluated in vitro and in vivo, with patritumab deruxtecan (patri-DXd) as a compar

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7

Beckford-Vera, Denis, Megan McCloskey, Jason Li, et al. "Abstract 5040: Novel HER3 targeting antibody radioconjugates, 225Ac-HER3 ARC and 177Lu-HER3 ARC, exhibit potent antitumor efficacy in HER3-positive solid tumors." Cancer Research 83, no. 7_Supplement (2023): 5040. http://dx.doi.org/10.1158/1538-7445.am2023-5040.

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Abstract Background: HER3 is a unique member of the EGFR family that collaborates with other EGFR receptors to induce tumorigenesis and drug resistance. Moreover, HER3 expression is linked to poor survival for patients with solid tumors. Despite HER3 being a rational cancer therapeutic target, no HER3-directed therapies have been approved for clinical use. However, new therapeutic strategies such as antibody drug conjugates (ADCs) are being investigated. Targeted radiotherapy, including radiolabeled antibodies (ARCs), is unique mechanistically by inducing cell death independent of biologic pat

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8

Toy, Weiyi, Dipti Thakkar, Roberto Magallanes, et al. "Abstract 5796: A HER3 antibody that uniquely blocks the HER3 heterodimerization interface effectively inhibits tumor growth in pre-clinical models with potentially oncogenic HER3 mutations." Cancer Research 84, no. 6_Supplement (2024): 5796. http://dx.doi.org/10.1158/1538-7445.am2024-5796.

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Abstract HER3 activation, via NRG1 ligand-dependent and -independent heterodimerization with HER2 or EGFR, has been associated with tumor progression and acquired resistance to therapies in multiple indications. HER3 mutations, detected in around 3% of cancer cases, may drive oncogenic signaling, leading to rapid tumor growth. Currently, there are no approved targeted therapies for HER3 mutations. Through analysis of real-world data and structural modelling of HER3 heterodimers, we identified four common HER3 mutations located within or close to the dimerization interface of HER3, suggesting a

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9

Beckford-Vera, Denis, Jason Li, Megan McCloskey, et al. "Abstract 3306: Targeting HER3 receptor positive cancers with a novel anti-HER3 antibody radioconjugate (ARC)." Cancer Research 82, no. 12_Supplement (2022): 3306. http://dx.doi.org/10.1158/1538-7445.am2022-3306.

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Abstract Background: HER3 overexpression is reported to be associated with poor survival in breast, ovarian, lung, gastric and prostate cancer. In addition, upregulation of HER3 in response to HER1 or HER2 targeted therapies, is implicated in the acquired resistance against these therapies. Therefore, effective targeting of HER3 can potentially overcome resistance and enhance therapeutic efficacy. Although a number of anti-HER3 antibodies have failed clinical testing with the development focus being shifted to other approaches such as antibody drug conjugates and bispecific antibodies, there a

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Scartozzi, M., A. Mandolesi, R. Giampieri, et al. "The role of HER-3 expression in the prediction of clinical outcome for advanced colorectal cancer patients receiving irinotecan/cetuximab." Journal of Clinical Oncology 29, no. 4_suppl (2011): 404. http://dx.doi.org/10.1200/jco.2011.29.4_suppl.404.

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404 Background: Preclinical data suggested that in presence of HER3 altered activation colorectal cancer cells may escape anti-EGFR mediated cell death. HER3 overexpression may then represent a key factor for resistance to anti-EGFR antibodies in colorectal cancer. The aim of our analysis was to investigate a possible correlation between HER3 expression and clinical outcome in KRAS wild-type advanced colorectal cancer receiving cetuximab and irinotecan. Methods: We retrospectively analyzed immunoreactivity for HER3 in KRAS wild-type advanced colorectal cancer patients receiving irinotecan-cetu

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Martinez Lago, Nieves, Ihab Abdulkader, Dora Insua Santamaria, et al. "Assessment and prognostic impact of a new classification using HER2 and HER3 status in resected gastric cancer in a european cohort." Journal of Clinical Oncology 36, no. 4_suppl (2018): 65. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.65.

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65 Background: HER2 status is a predictive biomarker to response to trastuzumab in metastatic gastric adenocarcinomas. However, relatively little is known about the role of HER2 and HER3 in the non-metastatic disease in European population. Methods: Immunohistochemical expression of HER2 was analyzed using DAKO-HercepTest™ and gene amplification using DAKO-DuoCISH kit; both was scored according to published reports. HER3 expressión was analyzed using HER3 clon DAK-H3-ICHER3 and scored as follows: 0 = no staining, 1+ = light staining, 2+ = moderate staining, and 3+ = strong staining. Slides wit

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Mukherjee, Sumit, Debbie Lewis, Jason Li, et al. "Abstract A149: Characterization of HER3 targeted radioligand therapy using molecular imaging." Molecular Cancer Therapeutics 22, no. 12_Supplement (2023): A149. http://dx.doi.org/10.1158/1535-7163.targ-23-a149.

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Abstract Background: Radioligand therapy (RLT) is an emerging treatment modality that has shown potential to improve survival in cancer patients that often have limited or non-effective therapeutic options. We previously demonstrated that anti-HER3 antibody radioconjugate (HER3 ARC) has antitumor efficacy against HER3 expressing tumor xenograft models. One important step in the early development of RLT is to understand the targeting properties and the distribution of the RLT in vivo. Non-invasive molecular imaging such as single photon emission computed tomography (SPECT) and positron emission

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Kucinski, Jack, Alexi Tallan, Matthew Kent, et al. "Abstract 2599: Biological consequences and mechanisms of neural signatures in fusion-positive rhabdomyosarcoma." Cancer Research 85, no. 8_Supplement_1 (2025): 2599. https://doi.org/10.1158/1538-7445.am2025-2599.

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Abstract The chimeric transcription factor PAX3::FOXO1 is a core dependency and monogenic driver of fusion-positive rhabdomyosarcoma, an aggressive pediatric soft-tissue sarcoma. PAX3::FOXO1 consists of the PAX3 DNA binding domains (paired and homeobox) and the FOXO1 transactivation domain. Despite the identification of the fusion-oncogene over thirty years ago, there are no targeted therapies for children suffering from this disease. The current therapeutic regimen consists of surgery, radiation, and general chemotherapy, which has been largely unsuccessful in improving patient outcomes. This

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Xie, Xuemei, Jangsoon Lee, Jon A. Fuson, et al. "Abstract LB088: Targeting ATR enhances the antitumor efficacy of patritumab deruxtecan (HER3-DXd) in tamoxifen-resistant ER+ breast cancer cells by reprogramming cell cycle progression." Cancer Research 82, no. 12_Supplement (2022): LB088. http://dx.doi.org/10.1158/1538-7445.am2022-lb088.

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Abstract Background: HER3, a member of the ErbB family of receptor tyrosine kinases that activate multiple oncogenic signaling pathways, is overexpressed in 50-70% of breast cancers (BC). HER3 mRNA levels are higher in ER+ breast tumors than in other molecular subtypes. Inhibition of ER activity using an antagonist increased HER3 protein expression and activation, which was essential for growth and survival of ER+ BC cells resistant to the ER antagonist. Therefore, therapeutically targeting HER3 with HER3-DXd, an antibody-drug conjugate (ADC) composed of a fully human anti-HER3 monoclonal anti

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Beckford-Vera, Denis, Jason Li, Caroline Jennings, et al. "Abstract 609: Anti-HER3 radioimmunotherapy enhances the anti-tumor effects of CD47 blockade in solid tumors." Cancer Research 82, no. 12_Supplement (2022): 609. http://dx.doi.org/10.1158/1538-7445.am2022-609.

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Abstract Background: Cancer immunotherapy strategies targeting blockade of the CD47-SIRPα immunosuppressive signal have made significant progress in recent years. However, monotherapies have not shown meaningful clinical responses in solid tumors. Therefore, therapeutic combinations are being explored to improve patient outcomes. CD47 is a macrophage checkpoint inhibitor that acts as a “don’t eat me” signal on cancer cells to evade innate immune detection and destruction. Targeted radiation to cancer cells will upregulate calreticulin (CRT), a pro-phagocytic “eat me” signal. We therefore hypot

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Chang, Chi-Son, Jung In Shim, Sun-Ju Byeon, et al. "Prognostic Significance of HER3 Expression in Patients with Cervical Cancer." Cancers 14, no. 9 (2022): 2139. http://dx.doi.org/10.3390/cancers14092139.

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HER3 has been recognized to have an oncogenic role in various types of cancer. However, its prognostic significance has not been elucidated in cervical cancer. The aim of this study was to investigate the prognostic significance of HER3 expression in cervical cancer using immunohistochemistry (IHC). HER3 immunohistochemical staining was performed on the tumor tissue samples of 336 cervical cancer patients. The association between the clinicopathological characteristics and patient survival analysis was assessed according to HER3 expression. HER3 IHC staining was positive in 31.0% (104/336) of

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Chang, Chi-Son, Jung In Shim, Sun-Ju Byeon, et al. "Prognostic Significance of HER3 Expression in Patients with Cervical Cancer." Cancers 14, no. 9 (2022): 2139. http://dx.doi.org/10.3390/cancers14092139.

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HER3 has been recognized to have an oncogenic role in various types of cancer. However, its prognostic significance has not been elucidated in cervical cancer. The aim of this study was to investigate the prognostic significance of HER3 expression in cervical cancer using immunohistochemistry (IHC). HER3 immunohistochemical staining was performed on the tumor tissue samples of 336 cervical cancer patients. The association between the clinicopathological characteristics and patient survival analysis was assessed according to HER3 expression. HER3 IHC staining was positive in 31.0% (104/336) of

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Amin, Dhara N., Natalia Sergina, Lionel Lim, Andrei Goga, and Mark M. Moasser. "HER3 signalling is regulated through a multitude of redundant mechanisms in HER2-driven tumour cells." Biochemical Journal 447, no. 3 (2012): 417–25. http://dx.doi.org/10.1042/bj20120724.

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HER2 (human epidermal growth factor receptor-2)-amplified tumours are characterized by constitutive signalling via the HER2–HER3 co-receptor complex. Although phosphorylation activity is driven entirely by the HER2 kinase, signal volume generated by the complex is under the control of HER3, and a large capacity to increase its signalling output accounts for the resiliency of the HER2–HER3 tumour driver and accounts for the limited efficacies of anti-cancer drugs designed to target it. In the present paper we describe deeper insights into the dynamic nature of HER3 signalling. Signalling output

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Rajendran, Rithika, Coen Johannes Gerardus Lap, Fayez Estephan, et al. "Prevalence of HER3 expression in prostate adenocarcinoma and its clinicopathological characteristics." Journal of Clinical Oncology 42, no. 16_suppl (2024): 5019. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.5019.

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5019 Background: Human epidermal growth factor receptor 3 (HER3) has been found upregulated in a wide variety of cancers and has been associated with disease progression and resistance to EGFR-targeted therapies in HER2-positive malignancies. Several studies have reported expression of HER3 in prostate cancer (PCa). Furthermore, concurrent expression of HER2 and HER3 in PCa has been associated with androgen resistance, development of metastatic disease, and less favorable outcomes. However, due to conflicting results, the exact nature of the relationship between HER2 and HER3 in PCa requires f

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Yonesaka, Kimio, Junko Tanizaki, Osamu Maenishi, et al. "Dynamics of HER3 and its correlated gene expression profile in EGFR-mutated NSCLC tumor treated with EGFR-TKI toward enhancing effectiveness of patritumab deruxtecan (HER3-DXd; U3-1402)." Journal of Clinical Oncology 40, no. 16_suppl (2022): e21175-e21175. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e21175.

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e21175 Background: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is a standard first-line therapy for activated EGFR-mutated non-small-cell lung cancer (NSCLC). Treatment options for patients with acquired EGFR-TKI resistance are limited. HER3 mediates EGFR-TKI resistance and is hence a promising target for anticancer treatment. Patritumab deruxtecan (HER3-DXd) is an antibody drug conjugate comprised of a fully human anti-HER3 IgG1 monoclonal antibody, covalently linked to a topoisomerase 1 inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable li

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Yonesaka, Kimio, Junko Tanizaki, Osamu Maenishi, et al. "Dynamics of HER3 and its correlated gene expression profile in EGFR-mutated NSCLC tumor treated with EGFR-TKI toward enhancing effectiveness of patritumab deruxtecan (HER3-DXd; U3-1402)." Journal of Clinical Oncology 40, no. 16_suppl (2022): e21175-e21175. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e21175.

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e21175 Background: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is a standard first-line therapy for activated EGFR-mutated non-small-cell lung cancer (NSCLC). Treatment options for patients with acquired EGFR-TKI resistance are limited. HER3 mediates EGFR-TKI resistance and is hence a promising target for anticancer treatment. Patritumab deruxtecan (HER3-DXd) is an antibody drug conjugate comprised of a fully human anti-HER3 IgG1 monoclonal antibody, covalently linked to a topoisomerase 1 inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable li

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Kim, Joori, Jeong-Oh Kim, Youn Soo Lee, et al. "The changes of HER3 expression in head and neck cancer patients treated with induction chemotherapy." Journal of Clinical Oncology 41, no. 16_suppl (2023): e18004-e18004. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e18004.

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e18004 Background: Erb-b2 receptor tyrosine kinase 3 (HER3) is broadly expressed in various types of cancer and is associated with poor prognosis. Recent evidence supports HER3 plays a role in acquired resistance to chemotherapy. The change of HER3 expression by chemotherapy in head and neck squamous cell carcinoma (HNSCC) remains unclear. Methods: We evaluated 95 patients with locally advanced HNSCC who had received induction chemotherapy (ICT) between 2009 and 2019. Immunohistochemical staining for HER3 was performed using formalin-fixed paraffin-embedded surgical specimens and biopsy sample

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Mishra, Rosalin, Mary Kate Kilroy, Wasim Feroz, Hima Patel, Samar Alanazi, and Joan T. Garrett. "Abstract 3916: role of her3 v104l mutation on tumor growth and her3 stabilization." Cancer Research 83, no. 7_Supplement (2023): 3916. http://dx.doi.org/10.1158/1538-7445.am2023-3916.

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Abstract We aimed to determine if naturally occurring HER3 mutations could drive oncogenic activity of HER2+ HCC1569 cells in which endogenous HER3 was knocked out using CRISPR-Cas9 technology. A series of HER3 mutations found in breast cancer patients (F94L, V104L, G284R, D297Y, T355I, and E928G) were introduced via lentiviral transduction and stable cell lines were generated in HER3 knock out (KO) HCC1569 cells and were maintained in 0.5 mg/mL puromycin. Our data indicated that cells stably transduced with HER3V104L mutation had significantly higher cell growth with higher p-HER3 expression

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Òdena, Andreu, Laia Monserrat, Fara Brasó-Maristany, et al. "Abstract P5-13-14: Antitumor activity of patritumab deruxtecan (HER3-DXd), a HER3-directed antibody drug conjugate (ADC) across a diverse panel of breast cancer (BC) patient-derived xenografts (PDXs)." Cancer Research 82, no. 4_Supplement (2022): P5–13–14—P5–13–14. http://dx.doi.org/10.1158/1538-7445.sabcs21-p5-13-14.

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Abstract Background: HER3 is overexpressed in 30-50% of breast cancers and has been associated with poor prognosis. Patritumab deruxtecan (HER3-DXd; U3-1402) is a HER3-directed ADC with a potent topoisomerase I (TOP1) inhibitor payload. A phase 1/2 study of HER3-DXd (NCT02980341) demonstrated promising antitumor activity in hormone receptor positive (HR+) metastatic BC patients with clinical activity observed across baseline levels of HER3 protein or mRNA expression. A window of opportunity clinical trial is currently ongoing to evaluate the biological activity of HER3-DXd in patients with tre

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Manickavasagar, Thubeena, Wei Yuan, Suzanne Carreira, et al. "HER3 expression and MEK activation in non-small-cell lung carcinoma." Lung Cancer Management 10, no. 2 (2021): LMT48. http://dx.doi.org/10.2217/lmt-2020-0031.

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Aim: We explore HER3 expression in lung adenocarcinoma (adeno-NSCLC) and identify potential mechanisms of HER3 expression. Materials & methods: Tumor samples from 45 patients with adeno-NSCLC were analyzed. HER3 and HER2 expression were identified using immunohistochemistry and bioinformatic interrogation of The Cancer Genome Atlas (TCGA). Results: HER3 was highly expressed in 42.2% of cases. ERBB3 copy number did not account for HER3 overexpression. Bioinformatic analysis of TCGA demonstrated that MEK activity score (a surrogate of functional signaling) did not correlate with HER3 ligands

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Rathore, Moeez Ghani, Wei Zhang, Michel'le Wright, et al. "Abstract 3177: Liver endothelium secreted LRG1 is a novel ligand of HER3 to promote metastatic colorectal cancer growth." Cancer Research 82, no. 12_Supplement (2022): 3177. http://dx.doi.org/10.1158/1538-7445.am2022-3177.

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Abstract Background: Liver is the most common site of developing distant metastasis in colorectal cancer (CRC). Patients with metastatic CRC (mCRC) have a 5-year survival rate at 14%. We previously showed that liver endothelial cells (EC), a key component of the liver microenvironment, secrete soluble factors to promote CRC growth and chemoresistance via activating human epidermal growth factor receptor (ERBB3, also known as HER3). However, we found that the ECs activated HER3 by a previously unknown mechanism that is independent of the established HER3 ligand neuregulins. Identifying a new HE

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Nishioka, Mariko, Chigusa Morizane, Mao Okada, et al. "HER3 expression status following systemic chemotherapy treatment in biliary tract cancers." Journal of Clinical Oncology 41, no. 16_suppl (2023): e16153-e16153. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e16153.

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e16153 Background: Erb-b2 receptor tyrosine kinase 3 (HER3) is frequently overexpressed in a variety of cancers. Activation of HER3 signaling serves an important role in promoting cell proliferation and is associated with chemoresistance. Thus, there is interest in exploring HER3 status of tumors as a potential prognostic and/or therapeutic target. Prior studies have reported HER3 status in various cancers after treatment with chemotherapy (CT). However, HER3 expression profile in biliary tract cancer (BTC) remains unknown. Here, we evaluated HER3 status of patients with BTC post CT. Methods:

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Kilroy, Mary Kate, SoYoung Park, Wasim Feroz, et al. "HER3 Alterations in Cancer and Potential Clinical Implications." Cancers 14, no. 24 (2022): 6174. http://dx.doi.org/10.3390/cancers14246174.

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In recent years, the third member of the HER family, kinase impaired HER3, has become a target of interest in cancer as there is accumulating evidence that HER3 plays a role in tumor growth and progression. This review focuses on HER3 activation in bladder, breast, colorectal, and lung cancer disease progression. HER3 mutations occur at a rate up to ~10% of tumors dependent on the tumor type. With patient tumors routinely sequenced for gene alterations in recent years, we have focused on HER3 mutations in bladder, breast, colon, and lung cancers particularly in response to targeted therapies a

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Xie, Xuemei, Jangsoon Lee, Jon A. Fuson, et al. "Abstract LB042: Targeting ATR enhances the antitumor efficacy of patritumab deruxtecan (HER3-DXd)in tamoxifen-resistant ER+ breast cancer cells by inducing DNA damage and apoptosis." Cancer Research 83, no. 8_Supplement (2023): LB042. http://dx.doi.org/10.1158/1538-7445.am2023-lb042.

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Abstract Background: HER3, a member of the ERBB family of receptor tyrosine kinases that activates multiple oncogenic signaling pathways, is overexpressed in 50-70% of breast cancers (BC). HER3 mRNA expression is highest in luminal (ER+) breast tumors. Approximately 30% of ER+ breast tumors are de novo resistant to tamoxifen. Therefore, therapeutically targeting HER3 with HER3-DXd, an antibody-drug conjugate (ADC) composed of a fully human anti-HER3 IgG1 monoclonal antibody (patritumab) covalently linked to a topoisomerase I (TOP I) inhibitor payload (deruxtecan) via a tetrapeptide-based cleav

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Mishra, Rosalin, Mary Kate Kilroy, Hima Patel, Samar Alanazi, and Joan T. Garrett. "Abstract 5412: Role of her3 mutations on breast cancer oncogenesis." Cancer Research 82, no. 12_Supplement (2022): 5412. http://dx.doi.org/10.1158/1538-7445.am2022-5412.

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Abstract We sought to determine if naturally occurring mutations in HER3 could drive oncogenic growth of HER3KO HER2+ HCC1569 cells in which endogenous HER3 has been eliminated via CRISPR-Cas9. A series of HER3 mutations identified in breast cancer patients (F94L, V104L, G284R, D297Y, T355I, and E928G) were introduced using lentiviral transduction and stable cell lines were generated in HER3KOHCC1569 cells via puromycin selection. We identified HER3V104L mutation to have higher cell proliferation and higher p-HER3 expression compared to wild-type (wt) and empty-vector (EV) HER3. We observed th

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Hwang, Hae Min, So Hyeon Kim, Sujin Ham, et al. "Abstract C120: Antitumor effect of HER3-DXd, an antibody-drug conjugate targeting HER3, in gastric cancer cell lines." Molecular Cancer Therapeutics 22, no. 12_Supplement (2023): C120. http://dx.doi.org/10.1158/1535-7163.targ-23-c120.

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Abstract Background: HER3, one of the HER family members, is expressed across various solid tumors and known to be an important oncogenic driver. HER3-DXd is an antibody-drug conjugate (ADC) that combines patritumab, an anti-HER3 antibody, and deruxtecan, a topoisomerase 1 inhibitor payload through peptide cleavable linker system. HER3-DXd has been shown to have anti-tumor effects in breast, non-small cell lung, and colorectal cancers, in vitro and in vivo, and is being evaluated in phase 2 and phase 3 clinical trials. However, the effect of HER3-DXd in gastric cancer and the mechanism of sens

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O'Hare, Thomas, Jaya Srivastava, Jaclyn Cleveland, Valerie Malyvanh Jansen, and David Dornan. "Abstract LB004: Preclinical discovery and characterization of EO-1022, a site-specific glycan-conjugated anti-HER3 vc-MMAE ADC for treating solid tumors." Cancer Research 85, no. 8_Supplement_2 (2025): LB004. https://doi.org/10.1158/1538-7445.am2025-lb004.

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Abstract The overexpression of HER3 in solid tumors is associated with poor prognosis. Therapies developed to target HER3-mediated signaling are often associated with resistance over time, highlighting the need to develop differentiated therapeutic strategies. To address the need for diversified targeted therapy options to treat HER3-positive solid tumors, we developed an antibody-drug conjugate, EO-1022, that selectively targets and eliminates HER3-expressing cancer cells. EO-1022 is comprised of the highly selective and clinically validated HER3 antibody, seribantumab, that is site-specifica

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Hong, Woojae, Jeon Hwang-Bo, Hyelin Jeon, et al. "A Comparative Study of the Hepatoprotective Effect of Centella asiatica Extract (CA-HE50) on Lipopolysaccharide/d-galactosamine-Induced Acute Liver Injury in C57BL/6 Mice." Nutrients 13, no. 11 (2021): 4090. http://dx.doi.org/10.3390/nu13114090.

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Acute liver failure (ALF) refers to the sudden loss of liver function and is accompanied by several complications. In a previous study, we revealed the protective effect of Centella asiatica 50% ethanol extract (CA-HE50) on acetaminophen-induced liver injury. In the present study, we investigate the hepatoprotective effect of CA-HE50 in a lipopolysaccharide/galactosamine (LPS-D-Gal)-induced ALF animal model and compare it to existing therapeutic silymarin, Lentinus edodes mycelia (LEM) extracts, ursodeoxycholic acid (UDCA) and dimethyl diphenyl bicarboxylate (DDB). Serum aspartate aminotransfe

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Tanner, Berno, Dirk Hasenclever, Katja Stern, et al. "ErbB-3 Predicts Survival in Ovarian Cancer." Journal of Clinical Oncology 24, no. 26 (2006): 4317–23. http://dx.doi.org/10.1200/jco.2005.04.8397.

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Background HER3 (erbB-3) is a member of the epidermal growth factor receptor (EGFR) family. After dimerization with other members of the EGFR family several signal transduction cascades can be activated, including phosphoinosite 3′-kinase (PI3-K)/Akt and extracellular signal-regulated kinase (ERK1/2). Here, we studied a possible association between HER3 expression and prognosis in patients with ovarian cancer. Methods Tumor tissue of 116 consecutive patients diagnosed with primary epithelial ovarian cancer between 1986 and 1995 was analyzed immunohistochemically for HER3 expression. A possible

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Òdena, Andreu, Laia Monserrat, Fara Brasó-Maristany, et al. "Abstract P2-03-25: Characterization of patritumab deruxtecan activity in breast cancer (BC) patient-derived xenograft (PDX) models." Clinical Cancer Research 31, no. 12_Supplement (2025): P2–03–25—P2–03–25. https://doi.org/10.1158/1557-3265.sabcs24-p2-03-25.

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Abstract Background: HER3 is overexpressed in 30-50% of breast cancers and is associated with poor prognosis. Patritumab deruxtecan (HER3-DXd; MK-1022) is a HER3-directed ADC with a potent topoisomerase I (TOP1) inhibitor payload. Clinical trials have demonstrated promising antitumor activity of HER3-DXd in metastatic and treatment-naïve breast cancer in all major subtypes (NCT02980341, NCT04610528), showing clinical activity across baseline levels of HER3 protein or mRNA expression. The identification of relevant biomarkers of response for this treatment remains an unmet clinical need. Here,

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Li, Zhuolin, Chengzhang Shang, Gao An, Chaoshe Guo, W. Frank An, and Yi Yang. "Abstract 2619: A novel EGFR × HER3-targeting bispecific antibody drug-conjugate, BCG019, demonstrates robust anti-tumor efficacy in preclinical evaluation." Cancer Research 84, no. 6_Supplement (2024): 2619. http://dx.doi.org/10.1158/1538-7445.am2024-2619.

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Abstract EGFR and HER3 are receptor tyrosine kinases that are highly expressed in multiple epithelial tumors. EGFR point mutations and small insertions within the kinase domain are common in lung cancer. HER3 is overexpressed in patients who are resistant to EGFR-TKI therapy, and is one of the common resistance mechanisms of EGFR and HER2-targeted therapy. We hypothesize that simultaneous targeting of EGFR and HER3 with a bispecific ADC will have the potential to overcome the resistance caused by HER3 after EGFR-targeted therapy and obtain better efficacy than the combination of EGFR monothera

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Maluvac, Hannah, Jordan Vellky, Karine Tawagi, Donald Vander Griend, and Natalie Marie Reizine. "Clinical implications of HER3 overexpression in a diverse patient cohort with prostate cancer." Journal of Clinical Oncology 43, no. 16_suppl (2025): 5081. https://doi.org/10.1200/jco.2025.43.16_suppl.5081.

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5081 Background: Prostate cancer (PCa) contributes to almost 15% of US cancer cases annually with significant racial disparities, where black men are more likely to develop and die from prostate cancer than any other cohort. Previously, we reported that HER 3/ERBB3 overexpression (OE) was enriched in the tumors of Black/ African American patients and was correlated with a unique androgen receptor signature as well as worse clinical outcomes. Here, we evaluate an expanded and more mature patient cohort to understand the effect of HER3 OE on clinical outcomes. In vitro experiments further suppor

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Cruz, Rodrigo G. B., Stephen F. Madden, Cathy E. Richards, et al. "Human Epidermal Growth Factor Receptor-3 Expression Is Regulated at Transcriptional Level in Breast Cancer Settings by Junctional Adhesion Molecule-A via a Pathway Involving Beta-Catenin and FOXA1." Cancers 13, no. 4 (2021): 871. http://dx.doi.org/10.3390/cancers13040871.

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The success of breast cancer therapies targeting the human epidermal growth factor receptor-2 (HER2) is limited by the development of drug resistance by mechanisms including upregulation of HER3. Having reported that HER2 expression and resistance to HER2-targeted therapies can be regulated by Junctional Adhesion Molecule-A (JAM-A), this study investigated if JAM-A regulates HER3 expression. Expressional alteration of JAM-A in breast cancer cells was used to test expressional effects on HER3 and its effectors, alongside associated functional behaviors, in vitro and semi-in vivo. HER3 transcrip

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Lim, Malcolm, Tam H. Nguyen, Colleen Niland, et al. "Landscape of Epidermal Growth Factor Receptor Heterodimers in Brain Metastases." Cancers 14, no. 3 (2022): 533. http://dx.doi.org/10.3390/cancers14030533.

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HER2+ breast cancer patients have an elevated risk of developing brain metastases (BM), despite adjuvant HER2-targeted therapy. The mechanisms underpinning this reduced intracranial efficacy are unclear. We optimised the in situ proximity ligation assay (PLA) for detection of the high-affinity neuregulin-1 receptor, HER2-HER3 (a key target of pertuzumab), in archival tissue samples and developed a pipeline for high throughput extraction of PLA data from fluorescent microscope image files. Applying this to a large BM sample cohort (n = 159) showed that BM from breast, ovarian, lung and kidney c

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Satake, Tomoyuki, Chigusa Morizane, Mao Okada, et al. "Abstract 3405: Changes in HER3 expression associated with chemotherapy for pancreatic cancer." Cancer Research 83, no. 7_Supplement (2023): 3405. http://dx.doi.org/10.1158/1538-7445.am2023-3405.

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Abstract Background: Currently, intense efforts towards the development of targeted therapy, including anti-HER3 strategies for cancer treatment, are being made. Recently, HER3 activation was linked to resistance to targeted therapies (EGFR/HER2/MEK/RAF) and hormonal therapy by upregulating HER3 expression after those treatments in several cancer types. However, HER3 expression profile in pancreatic cancer treatment is still unknown. Here, we evaluated the status of HER3 expression after chemotherapy for pancreatic cancer. Methods: Patients with pancreatic cancer who underwent chemotherapy bet

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Kurmasheva, Raushan, Peter Houghton, Vanessa Del Pozo, et al. "Abstract 1088: An evaluation of patritumab deruxtecan (HER3-DXd, U3-1402) against pediatric PDX models for hepatoblastoma and rhabdomyosarcoma - A report from the NCI PIVOT Program." Cancer Research 84, no. 6_Supplement (2024): 1088. http://dx.doi.org/10.1158/1538-7445.am2024-1088.

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Abstract Introduction: HER3-DXd is an ADC consisting of a fully human monoclonal antibody to HER3 attached to a topoisomerase I inhibitor payload (DXd, an exatecan derivative) that has demonstrated clinically meaningful efficacy with durable responses in adults with non-small cell lung cancer. Two childhood cancers with HER3 expression are rhabdomyosarcoma (RMS) and hepatoblastoma (HB), and the goal of this work was to evaluate the activity of HER3-DXd against PDX models for these cancer types. Methods: IHC testing was conducted on FFPE tissue (slides or TMA) using HER3/ErbB3 (D22C5) XP rabbit

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Romaniello, Donatella, Ilaria Marrocco, Nishanth Belugali Nataraj, et al. "Targeting HER3, a Catalytically Defective Receptor Tyrosine Kinase, Prevents Resistance of Lung Cancer to a Third-Generation EGFR Kinase Inhibitor." Cancers 12, no. 9 (2020): 2394. http://dx.doi.org/10.3390/cancers12092394.

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Although two growth factor receptors, EGFR and HER2, are amongst the best targets for cancer treatment, no agents targeting HER3, their kinase-defective family member, have so far been approved. Because emergence of resistance of lung tumors to EGFR kinase inhibitors (EGFRi) associates with compensatory up-regulation of HER3 and several secreted forms, we anticipated that blocking HER3 would prevent resistance. As demonstrated herein, a neutralizing anti-HER3 antibody we generated can clear HER3 from the cell surface, as well as reduce HER3 cleavage by ADAM10, a surface metalloproteinase. When

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Jacobs, Bart, Loredana Vecchione, Nicholas Hoe, et al. "Effect of EGFR inhibition on HER3/PI3K activation by feedback induction of ErbB heterodimers in cetuximab-sensitive colon cancer cells." Journal of Clinical Oncology 31, no. 15_suppl (2013): 3626. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3626.

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3626 Background: Although cetuximab treatment has been successful for the treatment of KRAS wild-type colorectal cancers, complete remissions are rarely seen in patients, leading ultimately to resistance. We hypothesized that in cetuximab-sensitive patients, the ErbB network is insufficiently targeted since network plasticity may occur. Methods: We have used EGFR-sensitive colorectal cancer cells and investigated ErbB network activity and adaptations by RTK arrays, western blot, and Collaborative Enzyme Enhance Reactive immunoassay (CEER). These were complemented by ErbB heterodimerization (HE

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Park, Yeon Hee, Hyun Ae Jung, Won Jin Chang, et al. "Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) patients who received taxane plus trastuzumab treatment." Journal of Clinical Oncology 31, no. 15_suppl (2013): 637. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.637.

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637 Background: The HER3 receptor is a key member of ErbB family and preferentially signals through the PI3K pathway. Formation of dimers between HER3 and HER2 seems to be crucial for HER2-driven signals in HER2 overexpressing tumors. Given the fact that HER2-HER3 is considered the most active signalling dimer of the ErbB system, HER3 activity may contribute to the resistance of trastuzumab. PTEN plays a well-established role in the negative regulation of the PI3K pathway. Our aim of this study was to investigate the role of HER3 and PTEN expression in patients with HER2 overexpressed MBC. Met

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Kilroy, Mary K., Rosalin Mishra, Anastasia Stupecki, Wasim Feroz, Samar Alanazi, and Joan T. Garrett. "Abstract 3988: The role of HER3 mutations in the progression of colon cancer and modulation of drug sensitivity and resistance." Cancer Research 83, no. 7_Supplement (2023): 3988. http://dx.doi.org/10.1158/1538-7445.am2023-3988.

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Abstract Colorectal cancer is a disease of the colon and rectum that will claim about 52,580 American lives in2022. The most common treatment of colorectal cancer is surgery plus chemotherapy, although thereare some FDA approved targeted therapies such as regorafenib (targeting VEGF) or cetuximab (targetingEGFR). EGFR, along with HER2, HER3, and HER4 are members of the HER family of receptor tyrosinekinases that upon homo- or heterodimerization activate downstream signaling, growth, and survivalpathways. In recent years, more attention has been paid to HER2 and HER3’s roles in colorectal cance

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Rathore, Moeez Ghani, Kimberly Curry, Christina Boutros, Zhenghe Wang, Jordan Winter, and Rui Wang. "Abstract 3082: The liver microenvironment promotes glycolysis in metastatic colorectal cancer by activating her3." Cancer Research 84, no. 6_Supplement (2024): 3082. http://dx.doi.org/10.1158/1538-7445.am2024-3082.

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Abstract Background: Liver metastasis occurs in ~80% of all metastatic colorectal cancer (mCRC) and the liver has a unique endothelial cell (EC)-rich microenvironment that promotes cancer cell survival. We previously reported that liver ECs secrete soluble factors to promote CRC growth via activating CRC-associated the HER3 signaling pathway. The present study reports that ECs promote mCRC growth by shifting cancer metabolism towards glycolysis and elucidates the involved signaling pathway. Methods: We performed mass spectrometry to profile the metabolic changes in mCRC treated with/without HE

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Raghav, Kanwal Pratap Singh, Takayuki Yoshino, Hiroya Taniguchi, et al. "An open-label, phase II study of patritumab deruxtecan (HER3-DXd, U3-1402) in patients (pts) with previously treated advanced/metastatic colorectal cancer (CRC)." Journal of Clinical Oncology 39, no. 3_suppl (2021): TPS157. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.tps157.

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TPS157 Background: Patritumab deruxtecan (HER3-DXd; U3-1402) is a novel, investigational antibody drug conjugate comprising an anti-HER3 monoclonal antibody, a tetrapeptide-based linker, and a topoisomerase I inhibitor payload. Ongoing clinical trials of HER3-DXd in pts with metastatic breast cancer or non-small cell lung cancer have shown promising clinical activity and acceptable safety. HER3 (human epidermal growth receptor 3), a member of the tyrosine kinase receptor family, is overexpressed in most CRC tumors and associated with an adverse prognosis. Significant tumor regression with HER3

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Kilroy, Mary K., Briley Park, Rosalin Mishra, Wasim Feroz, Cecilia Wischmeier, and Joan T. Garrett. "Abstract 7150: Molecular insights into the oncogenic influence between mutant HER3, mutant KRAS, and their synergistic interplay in colorectal cancer pathogenesis." Cancer Research 84, no. 6_Supplement (2024): 7150. http://dx.doi.org/10.1158/1538-7445.am2024-7150.

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Abstract Colorectal cancer (CRC) is a disease of the colon and rectum that will claim about 52,550 American lives in 2023. In recent years, more attention has been paid to HER2 and HER3’s roles in colorectal cancers, as they may cause resistance to targeted therapies. We are investigating the role of naturally co-occurring HER3 and KRAS mutations in colorectal cancer, as about 6% of all colorectal cancers contain a HER3 mutation and 41% contain a KRAS mutation. We have observed that there is a statistically significant co-occurrence of HER3 and KRAS mutations in CRCs while there is mutual excl

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Lyu, Hui, Congcong Tan, Yakun Wu, et al. "Abstract 4711: HER3 promotes triple-negative breast cancer progression by upregulating PHF8 via miR-34b-dependent mechanism." Cancer Research 85, no. 8_Supplement_1 (2025): 4711. https://doi.org/10.1158/1538-7445.am2025-4711.

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Abstract Introduction: Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous malignancy with poor prognosis and limited treatment options, presenting a significant clinical challenge. Current therapeutic strategies are insufficient to address the complexities of TNBC. In a previous study, we identified the human epidermal growth factor receptor 3 (HER3) signaling as a key driver of TNBC progression and a potential therapeutic target. However, the exact mechanisms through which HER3 signaling contributes to TNBC remain poorly understood. Methods: To explore the molecular

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Wang, Lina, Meijun Xiong, Xinju Gao, et al. "Abstract 2114: Enhancing therapeutic strategies for osimertinib-resistant EGFR-mutant NSCLC: A HER3 dual-payload ADC (dpADC) with topoisomerase I and EGFR tyrosine kinase inhibitor." Cancer Research 84, no. 6_Supplement (2024): 2114. http://dx.doi.org/10.1158/1538-7445.am2024-2114.

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Abstract Background: EGFR tyrosine kinase inhibitors (TKIs) have significantly improved the survival rate and the quality of life of the NSCLC patients with EGFR mutation in the first line setting. For example, Osimertinib, a potent third-generation EGFR TKI, has demonstrated exceptional efficacy in metastatic NSCLC with specific EGFR mutations. Despite its success, the emergence of drug resistance, often linked to elevated HER3 protein expression, remains a significant challenge. U3-1402 (HER3-Dxd), an HER3 ADC, demonstrates a promising result in managing Osimertinib-resistant NSCLC. It has b

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