Editorial Material
Medicine, Research & Experimental
Michael D. Gershon
Summary: The study identified genetic variants in ERBB3 and ERBB2 in 8 patients with defects in neural crest tissue, affecting the development of the enteric nervous system and highlighting the need for further mechanistic exploration.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Oncology
David J. Propper, Fangfei Gao, Mark P. Saunders, Debashis Sarker, John A. Hartley, Victoria J. Spanswick, Helen L. Lowe, Louise D. Hackett, Tony T. Ng, Paul R. Barber, Gregory E. Weitsman, Sarah Pearce, Laura White, Andre Lopes, Sharon Forsyth, Daniel Hochhauser
Summary: This study examined the toxicity and efficacy of high-dose pulsed AZD8931 combined with chemotherapy in metastatic colorectal cancer. Results showed acceptable toxicity and some patients had good response to the treatment. Furthermore, a reduction in circulating HER2/3 dimer was observed after treatment.
BRITISH JOURNAL OF CANCER
(2023)
Article
Endocrinology & Metabolism
Odelia Cooper, Vivien S. Bonert, Jeremy Rudnick, Barry D. Pressman, Janet Lo, Roberto Salvatori, Kevin C. J. Yuen, Maria Fleseriu, Shlomo Melmed
Summary: This study evaluated the effect of lapatinib, a tyrosine kinase inhibitor, on aggressive prolactinomas that are resistant to dopamine agonist therapy. While none of the participants achieved the primary endpoint, three showed stable disease and lapatinib was generally well tolerated with reversible side effects.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Oncology
Xuan Dai, Wenjun Ding, Yongshan He, Shiyong Huang, Yun Liu, Tingyu Wu
Summary: In this study, the efficacy and safety of regorafenib combined with PD-1 inhibitor in refractory MSS CRC were evaluated. The results showed that this combination treatment regimen is feasible and well-tolerated. ERBB2/ERBB3 mutation was identified as a potential predictive factor for treatment response.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Nindo B. Punturi, Sinem Seker, Vaishnavi Devarakonda, Aloran Mazumder, Rashi Kalra, Ching Hui Chen, Shunqiang Li, Tina Primeau, Matthew J. Ellis, Shyam M. Kavuri, Svasti Haricharan
Summary: Resistance to endocrine treatment in ER+ breast cancer patients is linked to activation of HER2 due to loss of mismatch repair, and inhibiting HER2 restores sensitivity to treatment. Loss of MutL and upregulation of HER2 are associated with sensitivity to HER inhibitors in ER+/HER2(-) patients.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Young-Sun Lee, Gyun Jee Song, Hee-Sook Jun
Summary: Betacellulin (BTC) has been shown to promote alpha-cell proliferation by interacting with ErbB-3 and ErbB-4 receptors, suggesting that these increased alpha-cells may serve as a potential source of new beta-cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Anna Adam-Artigues, Enrique J. Arenas, Alex Martinez-Sabadell, Fara Braso-Maristany, Raimundo Cervera, Eduardo Tormo, Cristina Hernando, Maria Teresa Martinez, Juan Carbonell-Asins, Soraya Simon, Jesus Poveda, Santiago Moragon, Sandra Zazo, Debora Martinez, Ana Rovira, Octavio Burgues, Federico Rojo, Joan Albanell, Begona Bermejo, Ana Lluch, Aleix Prat, Joaquin Arribas, Pilar Eroles, Juan Miguel Cejalvo
Summary: AXL overexpression is identified as an essential mechanism of trastuzumab resistance in HER2-positive breast cancer, and targeting AXL can restore trastuzumab response. AXL may serve as a predictive biomarker for prognosis in HER2-positive breast cancer patients. The study emphasizes the importance of targeting AXL in combination with anti-HER2 drugs to overcome resistance.
Review
Oncology
Joshua Z. Drago, Emanuela Ferraro, Nour Abuhadra, Shanu Modi
Summary: This review highlights the importance of targeting the HER2 oncogene in breast cancer treatment and discusses other members of the ERBB receptor family, such as EGFR and HER3. The synthesis of preclinical and clinical efforts provides insights into the successes and failures of targeting strategies. The review also proposes future directions, including new therapeutic modalities, combination strategies, and rational patient selection.
CANCER TREATMENT REVIEWS
(2022)
Review
Oncology
Chenzhe Ma, Xiao Wang, Jiwu Guo, Bo Yang, Yumin Li
Summary: Gastric cancer is the fifth most common cancer worldwide, and the treatment of advanced gastric cancer has seen limited progress. Human epidermal growth factor receptor 2 (HER2) has been found to contribute to the prognosis and pathogenesis of various cancers. Trastuzumab has emerged as the first-line targeted medication for treating HER2-positive advanced gastric cancer, but trastuzumab resistance has become a significant issue. This review focuses on the drug mechanisms of HER2-targeted therapy for gastric cancer and new detection techniques.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Jin-Soo Kim, Mi Young Kim, Sungyoul Hong
Summary: Metformin enhances the efficacy of trastuzumab in HER2+ gastric cancer cells, suggesting it as a potential therapy for HER2+ gastric cancer.
Article
Oncology
Melody A. Cobleigh, Charles L. Vogel, Debu Tripathy, Nicholas J. Robert, Susy Scholl, Louis Fehrenbacher, Janet M. Wolter, Virginia Paton, Steven Shak, Gracie Lieberman, Dennis J. Slamon
Summary: Recombinant humanized anti-HER2 monoclonal antibody as a single agent shows durable objective responses and good tolerability in women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Immunology
Catrin Heim, Laura M. Moser, Herman Kreyenberg, Halvard B. Bonig, Torsten Tonn, Winfried S. Wels, Elise Gradhand, Evelyn Ullrich, Michael T. Meister, Marian Groot Koerkamp, Frank C. P. Holstege, Jarno Drost, Jan-Henning Klusmann, Peter Bader, Michael Merker, Eva Rettinger
Summary: This study assesses the efficacy of the clinically usable CAR-engineered NK cell line NK-92/5.28.z against ErbB2-positive rhabdomyosarcoma (RMS) in vitro and in a metastatic xenograft mouse model. The results demonstrate that NK-92/5.28.z cells effectively kill RMS cells and significantly prolong survival and inhibit tumor progression in mice. These findings encourage further development of NK-92/5.28.z cells as off-the-shelf immunotherapy for the treatment of metastatic RMS.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Alison J. May, Aaron J. Mattingly, Eliza A. Gaylord, Nathan Griffin, Sonia Sudiwala, Noel Cruz-Pacheco, Elaine Emmerson, Seayar Mohabbat, Sara Nathan, Hanan Sinada, Isabelle M. A. Lombaert, Sarah M. Knox
Summary: Neuronal-epithelial cross-talk drives acinar specification through NRG1-ERBB3-mTORC2 signaling. NRG1-ERBB3 regulates the cellular programs of lineage progression, secretion, and polarization through the mTORC2 signaling pathway. This mechanism plays a crucial role in the formation of functional acini.
DEVELOPMENTAL CELL
(2022)
Review
Oncology
Homa Seyedmirzaei, Mahsa Keshavarz-Fathi, Sepideh Razi, Masoumeh Gity, Nima Rezaei
Summary: Breast cancer is a leading cause of cancer-induced deaths in women worldwide, with HER2 being an overexpressed growth factor in breast cancer. This review discusses different HER2-targeting immunotherapy approaches.
JOURNAL OF ONCOLOGY PHARMACY PRACTICE
(2021)
Article
Cell Biology
Mingang Hao, Syn Kok Yeo, Kevin Turner, Alexis Harold, Yongguang Yang, Xiaoting Zhang, Jun-Lin Guan
Summary: This study identified a mechanism by which disruption of FIP200-mediated autophagy can reduce HER2 expression on tumor cells and inhibit mammary tumorigenesis. Inhibition of sEVs secretion can rescue HER2 levels in tumor cells, suggesting a role for autophagy in promoting tumorigenesis in HER2+ breast cancer.
DEVELOPMENTAL CELL
(2021)
Article
Cell Biology
Juliana B. Candido, Jennifer P. Morton, Peter Bailey, Andrew D. Campbell, Saadia A. Karim, Thomas Jamieson, Laura Lapienyte, Aarthi Gopinathan, William Clark, Ewan J. McGhee, Jun Wang, Monica Escorcio-Correia, Raphael Zollinger, Rozita Roshani, Lisa Drew, Loveena Rishi, Rebecca Arkell, T. R. Jeffry Evans, Colin Nixon, Duncan I. Jodrell, Robert W. Wilkinson, Andrew V. Biankin, Simon T. Barry, Frances R. Balkwill, Owen J. Sansom
Article
Oncology
Nadine Nelson, Marta Lopez-Pelaez, Asis Palazon, Edmund Poon, Maike De La Roche, Simon Barry, Viia Valge-Archer, Robert W. Wilkinson, Simon J. Dovedi, Paul D. Smith
Article
Oncology
Stefanie R. Mullins, John P. Vasilakos, Katharina Deschler, Iwen Grigsby, Pete Gillis, Julius John, Matthew J. Elder, John Swales, Elina Timosenko, Zachary Cooper, Simon J. Dovedi, Andrew J. Leishman, Nadia Luheshi, James Elvecrog, Ashenafi Tilahun, Richard Goodwin, Ronald Herbst, Mark A. Tomai, Robert W. Wilkinson
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2019)
Article
Oncology
Shannon Burke, Amy Shergold, Matthew J. Elder, Justine Whitworth, Xing Cheng, Hong Jin, Robert W. Wilkinson, James Harper, Danielle K. Carroll
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2020)
Article
Multidisciplinary Sciences
Denice T. Y. Chan, Lesley Jenkinson, Stuart W. Haynes, Mark Austin, Agata Diamandakis, Daniel Burschowsky, Chitra Seewooruthun, Alexandra Addyman, Sebastian Fiedler, Stephanie Ryman, Jessica Whitehouse, Louise H. Slater, Ellen Gowans, Yoko Shibata, Michelle Barnard, Robert W. Wilkinson, Tristan J. Vaughan, Sarah Holt, Vincenzo Cerundolo, Mark D. Carr, Maria A. T. Groves
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Oncology
Susannah L. Hewitt, Dyane Bailey, John Zielinski, Ameya Apte, Faith Musenge, Russell Karp, Shannon Burke, Fabien Garcon, Ankita Mishra, Sushma Gurumurthy, Amanda Watkins, Kristen Arnold, James Moynihan, Eleanor Clancy-Thompson, Kathy Mulgrew, Grace Adjei, Katharina Deschler, Darren Potz, Gordon Moody, David A. Leinster, Steve Novick, Michal Sulikowski, Chris Bagnall, Philip Martin, Jean-Martin Lapointe, Han Si, Chris Morehouse, Maja Sedic, Robert W. Wilkinson, Ronald Herbst, Joshua P. Frederick, Nadia Luheshi
CLINICAL CANCER RESEARCH
(2020)
Article
Medicine, Research & Experimental
Darren J. Schofield, Jennifer Percival-Alwyn, Mateusz Rytelewski, John Hood, Raymond Rothstein, Leslie Wetzel, Kelly McGlinchey, Grace Adjei, Amanda Watkins, LeeAnn Machiesky, Weimin Chen, John Andrews, Maria Groves, Michelle Morrow, Ross A. Stewart, Andrew Leinster, Robert W. Wilkinson, Scott A. Hammond, Nadia Luheshi, Claire Dobson, Michael Oberst
Summary: Development of murine surrogate antibodies with pharmacologic properties similar to those of durvalumab and tremelimumab showed anti-tumor activity in select mouse syngeneic tumor models. This activity was not solely dependent on antibody-dependent cellular cytotoxicity, cellular phagocytosis effector function, or regulatory T-cell depletion, as antibodies engineered to lack these features also demonstrated activity, though at a lower level.
Article
Oncology
Simon J. Dovedi, Matthew J. Elder, Chunning Yang, Suzanne Sitnikova, Lorraine Irving, Anna Hansen, James Hair, Des C. Jones, Sumati Hasani, Bo Wang, Seock-Ah Im, Ben Tran, Deepa S. Subramaniam, Shelby D. Gainer, Kapil Vashisht, Arthur Lewis, Xiaofang Jin, Stacy Kentner, Kathy Mulgrew, Yaya Wang, Michael G. Overstreet, James Dodgson, Yanli Wu, Asis Palazon, Michelle Morrow, Godfrey J. Rainey, Gareth J. Browne, Frances Neal, Thomas Murray, Aleksandra D. Toloczko, William Dall'Acqua, Ikbel Achour, Daniel J. Freeman, Robert W. Wilkinson, Yariv Mazor
Summary: MEDI5752 is a novel monovalent bispecific antibody that enhances the clinical benefits of PD-1 blockade while reducing immune-related adverse events, leading to improved therapeutic outcomes. It represents a significant advancement in the rational design of cancer immunotherapy and shows promising potential in targeting PD-1(+) T cells with enhanced activity compared to conventional mAb combination strategies.
Article
Oncology
James Harper, Shannon Burke, Jon Travers, Nicola Rath, Andrew Leinster, Christel Navarro, Ruth Franks, Rebecca Leyland, Kathy Mulgrew, Kelly McGlinchey, Lee Brown, Simon J. Dovedi, Jens-Oliver Koopmann, Nicholas M. Durham, Xing Cheng, Hong Jin, Jim Eyles, Robert W. Wilkinson, Danielle Carroll
Summary: The recombinant NDVmuGM-CSF showed oncolytic activity and immune modulation in human tumor cells. In vivo experiments demonstrated antitumor effects with intratumoral injection, enhanced by co-treatment with immunomodulatory agents. Ex vivo profiling revealed changes in immune contexture and tumor microenvironment towards an immune-permissive state, supporting the utility of MEDI5395 in combination with other cancer treatments.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Oncology
Suzanne Isabelle Sitnikova, Sophie Munnings-Tomes, Elena Galvani, Stacy Kentner, Kathy Mulgrew, Chris Rands, Judit Espana Agusti, Tianhui Zhang, Kristina M. Ilieva, Guglielmo Rosignoli, Hormas Ghadially, Matthew J. Robinson, Tim Slidel, Robert W. Wilkinson, Simon J. Dovedi
Summary: A novel non-terminal tumor sampling method was developed and validated for biopsy of TME in mouse models, enabling repeated in-life sampling of subcutaneous flank tumors and linking TME biomarkers to treatment responses, which is not possible with current terminal sampling methods.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemical Research Methods
James Hair, Matthew J. Robinson, Robert W. Wilkinson, Simon J. Dovedi
Summary: This study provides a comprehensive understanding of the SICR profile of T and NK cells in solid tumors, guiding the design and application of future IO molecules.
Article
Oncology
Marta Lopez-Pelaez, Lucy Young, Mercedes Vazquez-Chantada, Nadine Nelson, Steve Durant, Robert W. Wilkinson, Edmund Poon, Miguel Gaspar, Viia Valge-Archer, Paul Smith, Simon J. Dovedi
Summary: This study demonstrates that targeting compensatory DNA repair pathways enhances the sensitivity of tumor cells to ATR inhibitor and DNA crosslinker, and activates dendritic cells (DCs) to increase tumor cell immunogenicity through the innate immune system activation. This provides a potential strategy to combat tumors.
Article
Multidisciplinary Sciences
Remi Samain, Oscar Maiques, Joanne Monger, Hoyin Lam, Juliana Candido, Samantha George, Nicola Ferrari, Leonie Kohihammer, Sophia Lunetto, Adrian Varela, Jose L. Orgaz, Felip Vilardell, Jorge Juan Olsina, Xavier Matias-Guiu, Debashis Sarker, Adrian Biddle, Frances R. Balkwill, Jim Eyles, Robert W. Wilkinson, Hemant M. Kocher, Fernando Calvo, Claire M. Wells, Victoria Sanz-Moreno
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to its high metastasis tendency and immunosuppressive microenvironment. The ROCK-Myosin II activity in PDAC cells supports an amoeboid invasive and immunosuppressive program, leading to in vivo metastasis. CD73, an immune checkpoint, is highly expressed in amoeboid PDAC cells and contributes to their invasive, metastatic, and immunomodulatory traits.
Article
Immunology
Damien J. Zanker, Alex J. Spurling, Natasha K. Brockwell, Katie L. Owen, Jasmine M. Zakhour, Tina Robinson, Hendrika M. Duivenvoorden, Paul J. Hertzog, Stefanie R. Mullins, Robert W. Wilkinson, Belinda S. Parker
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2020)
Article
Medicine, Research & Experimental
Mark Austin, Daniel Burschowsky, Denice T. Y. Chan, Lesley Jenkinson, Stuart Haynes, Agata Diamandakis, Chitra Seewooruthun, Alexandra Addyman, Sebastian Fiedler, Stephanie Ryman, Jessica Whitehouse, Louise H. Slater, Andreas V. Hadjinicolaou, Uzi Gileadi, Ellen Gowans, Yoko Shibata, Michelle Barnard, Teresa Kaserer, Pooja Sharma, Nadia M. Luheshi, Robert W. Wilkinson, Tristan J. Vaughan, Sarah V. Holt, Vincenzo Cerundolo, Mark D. Carr, Maria A. T. Groves