Article
Medicine, Research & Experimental
Maxwell Ducharme, Lucinda Hall, Whitney Eckenroad, Shelbie J. Cingoranelli, Hailey A. Houson, Luke Jaskowski, Chanelle Hunter, Benjamin M. Larimer, Suzanne E. Lapi
Summary: HER2 overexpression is associated with aggressive forms of breast cancer. Nanobodies, such as 2Rs15d, have shown potential as imaging agents and therapeutics for targeting HER2. In this study, the imaging and binding properties of 2Rs15d were evaluated, demonstrating high-quality visualization of HER2-positive tumors.
MOLECULAR PHARMACEUTICS
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ida Friberger, Joachim N. N. Nilsson, Li Lu, Jonathan Siikanen, Oscar Ardenfors, Stefan Milton, Erik Samen, Jeroen A. C. M. Goos, Mattias Carlsten, Staffan Holmin, Thuy A. A. Tran
Summary: The study assessed the in vivo biodistribution of cells in rats using two radiotracers, [Zr-89]Zr-(oxinate)(4) and [Zr-89]Zr-DFO-NCS. The results showed that the behavior of the radiolabelled cells in vivo was influenced by the labelling method. [Zr-89]Zr-(oxinate)(4) labelled cells had higher liver uptake, while [Zr-89]Zr-DFO-NCS labelled cells showed prolonged accumulation in the lungs. The difference in lung and liver uptake continued until day 7. Furthermore, dosimetry calculations showed different effective doses for the two radiotracers. The study highlights the importance of radiotracer labelling in cell biodistribution studies using PET.
Article
Cell Biology
Zicong Gao, Xingxing Han, Yuying Zhu, He Zhang, Ran Tian, Zhiyong Wang, Yanfen Cui, Zhaosong Wang, Ruifang Niu, Fei Zhang
Summary: Our study demonstrates that exosomal EphA2 plays a key role in transferring aggressive phenotype between cancer cells without direct cell-cell contact. The increase of EphA2 in drug-resistant cell-derived exosomes may be an important mechanism of chemotherapy/drug resistance-induced breast cancer progression. Exosomal EphA2 activates ERK1/2 signaling, promoting breast cancer progression through the Ephrin A1-dependent reverse pathway.
CELL DEATH & DISEASE
(2021)
Article
Materials Science, Biomaterials
Pyeong Seok Choi, Jun Young Lee, Seung Dae Yang, Jeong Hoon Park
Summary: A novel chelator-free Zr-89-IONC with rice-shaped morphology was developed and coated with polyethyleneimine (PEI) and polyvinylpyrrolidone (PVP) to improve cancer targeting efficacy. Positron emission tomography measurements confirmed that only PVP-coated Zr-89-IONC reached the tumor region, while non-coated and PEI coated ones tended to be cleared in the liver and spleen. The Zr-89-incorporated iron oxide nanocomposite showed stability for radiolabeling, making it a potential carrier for specific cancer cell targeting.
JOURNAL OF MATERIALS CHEMISTRY B
(2021)
Article
Oncology
Hui K. Gan, Sagun Parakh, F. T. Lee, Niall C. Tebbutt, Malaka Ameratunga, Sze Ting Lee, Graeme J. O'Keefe, Sylvia J. Gong, Christine Vanrenen, Jaren Caine, Mara Giovannetti, Carmel Murone, Fiona E. Scott, Nancy Guo, Ingrid J. G. Burvenich, Cameron Paine, Mary J. Macri, Masakatsu Kotsuma, Giorgio Senaldi, Ralph Venhaus, Andrew M. Scott
Summary: This study reports a phase I dose escalation and biodistribution study of DS-8895a, an anti-EphA2 antibody, in patients with advanced EphA2 positive cancers. The results show limited therapeutic efficacy of DS-8895a and highlight the importance of biodistribution studies in drug development.
INVESTIGATIONAL NEW DRUGS
(2022)
Review
Biochemistry & Molecular Biology
Kalin Wilson, Eileen Shiuan, Dana M. Brantley-Sieders
Summary: Over 25 years of research have identified EphA2 receptor tyrosine kinase as a promising molecular target for cancer treatment. Various targeting strategies, including drugs like dasatinib, therapeutic antibodies, and approaches harnessing antitumor immunity against EphA2-expressing cancer cells, have shown potential in preclinical studies. Completed and ongoing clinical trials are highlighting the promise and challenges of targeting EphA2 in cancer therapy.
Review
Biochemistry & Molecular Biology
Ping Zhao, Dewei Jiang, Yunchao Huang, Ceshi Chen
Summary: EphA2, a receptor tyrosine kinase overexpressed in human breast cancers, plays important roles in malignant breast progression and has become a promising therapeutic target for breast cancer treatment.
JOURNAL OF GENETICS AND GENOMICS
(2021)
Article
Biochemistry & Molecular Biology
Linfeng Mao, Weijie Yuan, Kaimei Cai, Chen Lai, Changhao Huang, Yi Xu, Shangwei Zhong, Chen Yang, Ran Wang, Pengwei Zeng, Heyuan Huang, Zhikang Chen, Zihua Chen
Summary: EphA2, YES1, and ANXA2 form a signaling axis that promotes gastric cancer invasion and metastasis. Overexpression of YES1 increases invasion and migration of gastric cancer cells, while knockdown of ANXA2 decreases these processes.
Article
Biochemistry & Molecular Biology
Santosh K. K. Dasari, Robiya Joseph, Sujanitha Umamaheswaran, Lingegowda S. S. Mangala, Emine Bayraktar, Cristian Rodriguez-Aguayo, Yutuan Wu, Nghi Nguyen, Reid T. T. Powell, Mary Sobieski, Yuan Liu, Mamur A. A. Chowdhury, Paola Amero, Clifford Stephan, Gabriel Lopez-Berestein, Shannon N. N. Westin, Anil K. K. Sood
Summary: EphA2 tyrosine kinase is upregulated in many cancers and correlated with poor patient survival. A chemical screen identified Wee1 kinase inhibitor as a synergistic partner to EphA2-targeted therapeutics. Combination treatment showed enhanced anti-tumor response in endometrial cancer, suggesting the potential of Wee1 inhibition in improving EphA2-targeted therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Veronika Kozlovskaya, Maxwell Ducharme, Maksim Dolmat, James M. Omweri, Volkan Tekin, Suzanne E. Lapi, Eugenia Kharlampieva
Summary: Researchers developed a 60 nm-sized polymer vesicle that can be easily imaged using positron emission tomography (PET) without the need for chelators. By modifying the vesicle surface with the degradable tannic acid (TA) and targeting antibody trastuzumab (Tmab), the vesicles were able to specifically target HER2-positive breast cancer cells. These radiolabeled vesicles hold great potential for precise drug delivery and therapy.
Article
Nanoscience & Nanotechnology
Pyeong Seok Choi, Jun Young Lee, Jung Ho Chae, Thaddeus Wadas, Zhen Cheng, Min Goo Hur, Jeong Hoon Park
Summary: Cherenkov radiation is being studied for cancer detection and therapy. Nanoparticles are used to develop a theranostic platform for visualizing therapy delivery and generating reactive oxygen species to kill cancer cells.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Oncology
Mark Primeaux, Xiangdong Liu, Saiprasad Gowrikumar, Iram Fatima, Kurt W. Fisher, Dhundy Bastola, Alex J. Vecchio, Amar B. Singh, Punita Dhawan
Summary: High expression of CLDN1 in CRC is associated with cancer stemness and chemoresistance signaling pathways. CLDN1 promotes stemness and chemoresistance through a direct interaction with EPHA2 tyrosine kinase.
Article
Medicine, Research & Experimental
Baoai Han, He Zhang, Ruinan Tian, Hui Liu, Zhaosong Wang, Zhiyong Wang, Jianfei Tian, Yanfen Cui, Sixin Ren, Xiaoyan Zuo, Ran Tian, Ruifang Niu, Fei Zhang
Summary: This study reveals a novel mechanism of intercellular communication between breast cancer cells and endothelial cells in the tumor microenvironment through exosomal EPHA2, which promotes angiogenesis and metastasis. Targeting exosomal EPHA2-AMPK signaling could be a potential strategy for breast cancer therapy.
Article
Chemistry, Medicinal
Alix Troster, Nathalie Jores, Konstantin S. Mineev, Sridhar Sreeramulu, Michael DiPrima, Giovanna Tosato, Harald Schwalbe
Summary: This concept paper describes the general strategies for EPHA2 inhibition with small molecules and summarizes the potential of targeting EPHA2 in CRC. EPHA2 plays a crucial role in the development and resistance mechanisms of CRC.
Article
Astronomy & Astrophysics
X. Y. Gao, Y. Li, C. P. Shen, I Adachi, H. Aihara, D. M. Asner, H. Atmacan, T. Aushev, R. Ayad, P. Behera, K. Belous, M. Bessner, V Bhardwaj, B. Bhuyan, T. Bilka, A. Bobrov, D. Bodrov, G. Bonvicini, J. Borah, A. Bozek, T. E. Browder, A. Budano, M. Campajola, M-C Chang, P. Chang, A. Chen, B. G. Cheon, K. Chilikin, H. E. Cho, K. Cho, S-J Cho, S-K Choi, Y. Choi, S. Choudhury, D. Cinabro, S. Cunliffe, S. Das, G. De Pietro, R. Dhamija, F. Di Capua, J. Dingfelder, Z. Dolezal, T. Dong, D. Dossett, D. Epifanov, T. Ferber, A. Frey, B. G. Fulsom, R. Garg, V Gaur, N. Gabyshev, A. Giri, P. Goldenzweig, T. Gu, Y. Guan, K. Gudkova, C. Hadjivasiliou, S. Halder, O. Hartbrich, K. Hayasaka, H. Hayashii, M. T. Hedges, W-S Hou, C-L Hsu, T. Iijima, K. Inami, G. Inguglia, A. Ishikawa, R. Itoh, M. Iwasaki, Y. Iwasaki, W. W. Jacobs, E-J Jang, S. Jia, Y. Jin, K. K. Joo, J. Kahn, A. B. Kaliyar, K. H. Kang, G. Karyan, T. Kawasaki, H. Kichimi, C. Kiesling, C. H. Kim, D. Y. Kim, K-H Kim, Y-K Kim, P. Kodys, T. Konno, A. Korobov, S. Korpar, E. Kovalenko, P. Krizan, R. Kroeger, P. Krokovny, T. Kuhr, R. Kumar, K. Kumara, A. Kuzmin, Y-J Kwon, Y-T Lai, T. Lam, J. S. Lange, M. Laurenza, S. C. Lee, C. H. Li, J. Li, L. K. Li, Y. B. Li, L. Li Gioi, J. Libby, K. Lieret, D. Liventsev, A. Martini, M. Masuda, T. Matsuda, D. Matvienko, S. K. Maurya, F. Meier, M. Merola, F. Metzner, K. Miyabayashi, R. Mizuk, G. B. Mohanty, R. Mussa, M. Nakao, Z. Natkaniec, A. Natochii, L. Nayak, M. Niiyama, N. K. Nisar, S. Nishida, K. Ogawa, S. Ogawa, H. Ono, P. Oskin, P. Pakhlov, G. Pakhlova, T. Pang, S. Pardi, H. Park, S-H Park, S. Patra, S. Paul, T. K. Pedlar, R. Pestotnik, L. E. Piilonen, T. Podobnik, V Popov, E. Prencipe, M. T. Prim, M. Rohrken, A. Rostomyan, N. Rout, G. Russo, D. Sahoo, S. Sandilya, A. Sangal, L. Santelj, T. Sanuki, V Savinov, G. Schnell, Y. Seino, K. Senyo, M. E. Sevior, M. Shapkin, C. Sharma, J-G Shiu, F. Simon, J. B. Singh, A. Sokolov, E. Solovieva, S. Stanic, M. Staric, Z. S. Stottler, M. Sumihama, T. Sumiyoshi, M. Takizawa, U. Tamponi, K. Tanida, F. Tenchini, M. Uchida, K. Uno, S. Uno, P. Urquijo, Y. Usov, R. Van Tonder, G. Varner, A. Vinokurova, E. Waheed, E. Wang, M-Z Wang, X. L. Wang, M. Watanabe, S. Watanuki, E. Won, X. Xu, B. D. Yabsley, W. Yan, S. B. Yang, H. Ye, J. H. Yin, C. Z. Yuan, Y. Zhai, Z. P. Zhang, V Zhilich, V Zhukova
Summary: A search for the double-heavy tetraquark state candidates Xcc(x) over bar(s) over bar decaying to Ds+Ds+ and D-s*+D-s(*)+ is conducted for the first time using large data samples. No significant signals are observed, and constraints on the product branching fractions and Born cross sections are obtained.
Article
Oncology
Andrew B. Lassman, Stephanie L. Pugh, Tony J. C. Wang, Kenneth Aldape, Hui K. Gan, Matthias Preusser, Michael A. Vogelbaum, Erik P. Sulman, Minhee Won, Peixin Zhang, Golnaz Moazami, Marian S. Macsai, Mark R. Gilbert, Earle E. Bain, Vincent Blot, Peter J. Ansell, Suvajit Samanta, Madan G. Kundu, Terri S. Armstrong, Jeffrey S. Wefel, Clemens Seidel, Filip Y. de Vos, Sigmund Hsu, Andres F. Cardona, Giuseppe Lombardi, Dmitry Bentsion, Richard A. Peterson, Craig Gedye, Veronique Bourg, Antje Wick, Walter J. Curran, Minesh P. Mehta
Summary: The use of depatux-m in newly diagnosed glioblastomas (GBMs) with epidermal growth factor receptor gene amplification (EGFR-amp) did not improve overall survival (OS), but showed a longer progression-free survival. There were safety risks associated with the treatment, leading to treatment discontinuation for some patients.
Article
Oncology
Macarena de la Fuente, Howard Colman, Mark Rosenthal, Brian A. Van Tine, Danijela Levacic, Tobias Walbert, Hui K. Gan, Maria Vieito, Mohammed M. Milhem, Kathryn Lipford, Sanjeev Forsyth, Sylvie M. Guichard, Yelena Mikhailov, Alexander Sedkov, Julie Brevard, Patrick F. Kelly, Hesham Mohamed, Varun Monga
Summary: Olutasidenib, a drug designed to target relapsed/refractory gliomas with IDH1(R132X) mutation, has demonstrated good tolerability and preliminary clinical activity in patients.
Editorial Material
Clinical Neurology
Hui K. Gan
NEURO-ONCOLOGY PRACTICE
(2023)
Review
Oncology
Maximilian J. Mair, Rupert Bartsch, Emilie Le Rhun, Anna S. Berghoff, Priscilla K. Brastianos, Javier Cortes, Hui K. Gan, Nancy U. Lin, Andrew B. Lassman, Patrick Y. Wen, Michael Weller, Martin van den Bent, Matthias Preusser
Summary: Antibody-drug conjugates (ADCs) have shown efficacy in various cancers, but their activity in the central nervous system (CNS) may be limited by the blood-brain barrier. This review summarizes the available clinical data on ADCs against primary and secondary brain tumors and ongoing trials. It also discusses the physical, biological, and molecular determinants of ADCs' CNS activity and potential strategies to improve drug delivery to brain tumors.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Review
Oncology
Hui Kong Gan, Bryan W. W. Day, Rosemary Harrup, Terrance G. G. Johns, Zarnie Lwin, Andrew Mark Scott, Hao-Wen Sim, Eng-Siew Koh
Summary: This review discusses the challenges and barriers faced in the development of drugs for neuro-oncology trials at various stages and the impact on patient outcomes over the past 30 years. Strategies to address these issues include improved preclinical testing, focus on blood-brain barrier penetrance and targeting key biological processes, adoption of innovative trial designs, and stronger translational focus. The implementation of these strategies requires coordinated efforts between clinicians, scientists, industry, and funding/regulator bodies.
CURRENT ONCOLOGY REPORTS
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Nathaniel Barry, Roslyn J. Francis, Martin A. Ebert, Eng-Siew Koh, Pejman Rowshanfarzad, Ghulam Mubashar Hassan, Jake Kendrick, Hui K. Gan, Sze T. Lee, Eddie Lau, Bradford A. Moffat, Greg Fitt, Alisha Moore, Paul Thomas, David A. Pattison, Tim Akhurst, Ramin Alipour, Elizabeth L. Thomas, Edward Hsiao, Geoffrey P. Schembri, Peter Lin, Tam Ly, June Yap, Ian Kirkwood, Wilson Vallat, Shahroz Khan, Dayanethee Krishna, Stanley Ngai, Chris Yu, Scott Beuzeville, Tow C. Yeow, Dale Bailey, Olivia Cook, Angela Whitehead, Rachael Dykyj, Alana Rossi, Andrew Grose, Andrew M. Scott
Summary: The FET PET trial in Australia aimed to evaluate the role of FET PET in managing glioblastoma patients. The study found that there was considerable variability in tumor delineation and interpretation, but the overall results were reliable.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Review
Oncology
Ravi Marwah, Daniel Xing, Timothy Squire, Yu Yang Soon, Hui K. Gan, Sweet Ping Ng
Summary: This review compares reirradiation (reRT), systemic therapy, and combination therapy (reRT & systemic therapy) in patients with recurrent high-grade glioma (rHGG) in terms of overall survival (OS), progression-free survival (PFS), adverse effects (AEs), and quality of life (QoL). The study found that combination therapy may improve OS and PFS with acceptable toxicities. Additionally, combining bevacizumab with reRT prophylactically reduces radionecrosis.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Christian Werner Wichmann, Ingrid Julienne Georgette Burvenich, Nancy Guo, Angela Rigopoulos, Alexander McDonald, Diana Cao, Graeme Joseph O'Keefe, Sylvia Jie Gong, Hui Kong Gan, Fiona Elizabeth Scott, Nabendu Pore, Steven Coats, Andrew Mark Scott
Summary: This study investigated the biodistribution properties of the anti-ASCT2 antibody drug conjugates (ADCs) MEDI7247 and MEDI7519, as well as an isotype control ADC, using ^89Zr radiolabeling. The results showed that both MEDI7247 and MEDI7519 displayed specific tumor uptake but exhibited faster blood clearance and non-specific localization in the liver. This highlights the importance of nuclear medicine imaging techniques in the early preclinical assessment of drug specificity.
NUCLEAR MEDICINE AND BIOLOGY
(2023)
Article
Medicine, General & Internal
Eng-Siew Koh, Hui K. Gan, Clare Senko, Roslyn J. Francis, Martin Ebert, Sze Ting Lee, Eddie Lau, Mustafa Khasraw, Anna K. Nowak, Dale L. Bailey, Bradford A. Moffat, Greg Fitt, Rodney J. Hicks, Robert Coffey, Roel Verhaak, Kyle M. Walsh, Elizabeth H. Barnes, Richard De Abreu Lourenco, Mark Rosenthal, Lucas Adda, Farshad Foroudi, Arian Lasocki, Alisha Moore, Paul A. Thomas, Paul Roach, Michael Back, Robyn Leonard, Andrew M. Scott
Summary: FET-PET has the potential to impact adjuvant radiotherapy planning, differentiate between treatment-induced pseudoprogression and true tumor progression, and predict prognosis in glioblastoma management. The FIG study is a multicenter phase II study aiming to investigate the impact of FET-PET versus standard MRI on radiotherapy volume delineation and the accuracy and management impact of FET-PET in distinguishing pseudoprogression from true tumor progression.
Article
Cell Biology
Sophia Frentzas, Hui K. Gan, Rasha Cosman, Jermaine Coward, Ben Tran, Michael Millward, Yiting Zhou, Wenjing Wang, Dennis Xia, Zhongmin Maxwell Wang, Baiyong Li, Michelle Xia, Jayesh Desai
Summary: This study evaluates the safety and efficacy of Cadonilimab in patients with advanced solid tumors. The results demonstrate good tolerability and promising efficacy of Cadonilimab in some patients.
CELL REPORTS MEDICINE
(2023)
Article
Oncology
Benedito A. Carneiro, Kyriakos P. Papadopoulos, John H. Strickler, Andrew B. Lassman, Saiama N. Waqar, Young Kwang Chae, Jyoti D. Patel, Einat Shacham-Shmueli, Karen Kelly, Mustafa Khasraw, Christine M. Bestvina, Ryan Merrell, Kevin Huang, Harisha Atluri, Peter Ansell, Rachel Li, Janet Jin, Mark G. Anderson, Edward B. Reilly, Gladys Morrison-Thiele, Kalpesh Patel, Randy R. Robinson, Martha R. Neagu Aristide, Hui K. Gan
Summary: Ser-T monotherapy demonstrated tolerable safety profile with minimal antitumor activity observed in patients with glioblastoma at recommended phase II dose.
NEURO-ONCOLOGY ADVANCES
(2023)
Article
Chemistry, Multidisciplinary
Catherine G. Fitzgerald Dickmann, Alexander F. F. McDonald, Nhi Huynh, Angela Rigopoulos, Zhanqi Liu, Nancy Guo, Laura D. D. Osellame, Michael A. A. Gorman, Michael W. W. Parker, Hui K. K. Gan, Andrew M. M. Scott, Uwe Ackermann, Ingrid J. G. Burvenich, Jonathan M. M. White
Summary: A novel molecule, [F-18]BiPET-2, radiolabelled with positron emitting fluorine-18, has been developed and evaluated in vitro and preclinically in glioblastoma models.
CHEMICAL COMMUNICATIONS
(2023)
Review
Biotechnology & Applied Microbiology
Hui K. Gan, Sagun Parakh, Laura D. Osellame, Lawrence Cher, Anthony Uccellini, Umbreen Hafeez, Siddharth Menon, Andrew M. Scott
Summary: ADCs have shown great potential in the treatment of brain tumors by combining specific targeting with effective drug payloads. This review discusses the different classes of ADCs tested in primary brain tumors and evaluates their efficacy and limitations. The valuable insights gained from previous trials provide a strong rationale for further development of ADCs tailored for the unique biology of brain tumors.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2023)
Article
Oncology
Hao-Wen Sim, Luke Wachsmuth, Elizabeth H. Barnes, Sonia Yip, Eng-Siew Koh, Merryn Hall, Ross Jennens, David M. Ashley, Roel G. Verhaak, Amy B. Heimberger, Mark A. Rosenthal, Elizabeth J. Hovey, Benjamin M. Ellingson, Annette Tognela, Hui K. Gan, Helen Wheeler, Michael Back, Kerrie L. Mcdonald, Anne Long, Katharine Cuff, Stephen Begbie, Craig Gedye, Anna Mislang, Hien Le, Margaret O. Johnson, Benjamin Y. Kong, John R. Simes, Zarnie Lwin, Mustafa Khasraw
Summary: The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients aged 65 years and older with glioblastoma. However, the results showed that nivolumab did not significantly improve overall survival in these patients. Three grade 3 immune-related adverse events were reported in the experimental arm.
NEURO-ONCOLOGY ADVANCES
(2023)