Article
Oncology
Shenbo Chen, Liangwang Yang, Zhengzheng Li, Shenghua Zhuo, Bo Yan, Zhaoteng Zhang, Jinben Zhang, Haizhong Feng, Kun Yang
Summary: EGFR/EGFR variant III (EGFRvIII) glioblastoma with co-expression of EGFR and GLUT3 is associated with worse overall survival. Experimental evidence suggests that EGFRvIII and GLUT3 cooperate in promoting tumorigenesis, indicating a potential therapeutic target.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Justin Choi, Zachary A. Bordeaux, Jaimie McKeel, Cory Nanni, Nishadh Sutaria, Gabriella Braun, Cole Davis, Meghan N. Miller, Martin P. Alphonse, Shawn G. Kwatra, Cameron E. West, Madan M. Kwatra
Summary: This study examined the effect of a novel anti-cancer agent, GZ17-6.02, on two types of glioblastoma stem cells. The results showed that GZ17-6.02 inhibited cell growth and downregulated pathways related to steroid synthesis and cell cycle progression. Animal experiments also demonstrated that GZ17-6.02 inhibited glioblastoma growth. The study concludes that GZ17-6.02 is a promising drug for inhibiting the growth of a subset of glioblastomas.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Rameshwar Patil, Tao Sun, Mohammad Harun Rashid, Liron L. Israel, Arshia Ramesh, Saya Davani, Keith L. Black, Alexander Ljubimov, Eggehard Holler, Julia Y. Ljubimova
Summary: This study aimed to develop multifunctional nanomedicines for treating glioblastoma using combination therapy targeting multiple molecular markers. By utilizing multifunctional nanopolymers, the growth of GBM cells was effectively inhibited, significantly increasing the survival rate of tumor-bearing animals.
Article
Oncology
Andres F. Cardona, Daniel Jaramillo-Velasquez, Alejandro Ruiz-Patino, Carolina Polo, Enrique Jimenez, Fernando Hakim, Diego Gomez, Juan Fernando Ramon, Hernando Cifuentes, Juan Armando Mejia, Fernando Salguero, Camila Ordonez, Alvaro Munoz, Sonia Bermudez, Nicolas Useche, Diego Pineda, Luisa Ricaurte, Zyanya Lucia Zatarain-Barron, July Rodriguez, Jenny Avila, Leonardo Rojas, Elvira Jaller, Carolina Sotelo, Juan Esteban Garcia-Robledo, Nicolas Santoyo, Christian Rolfo, Rafael Rosell, Oscar Arrieta
Summary: This study targeted adult patients with recurrent GB enriched for EGFR amplification and EGFRvIII mutation, using osimertinib/bevacizumab combination therapy, and found some patients experienced long-lasting meaningful benefits. Resistance patterns after treatment included known mechanisms in EGFR regulation, contributing to understanding and targeting this pathway in a rational stepwise manner.
JOURNAL OF NEURO-ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Zesheng Li, Bo Wang, Jianjian Wu, Lei Han
Summary: Tricyclic antidepressants are safe and reliable therapeutic agents that can be used for cancer treatment, especially glioblastoma. However, the specific mechanism by which they affect the tumor microenvironment of glioblastoma is still unclear.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Fei Tong, Ji-xing Zhao, Zi-yuan Fang, Xiao-teng Cui, Dong-yuan Su, Xing Liu, Jun-hu Zhou, Guang-xiu Wang, Zhi-jun Qiu, Shi-zhong Liu, Jun-qi Fu, Chun-sheng Kang, Jia-chong Wang, Qi-xue Wang
Summary: Based on CRISPR-Cas9 library screening, we found that MUC1-C is essential for EGFRvIII glioma cell survival and TMZ resistance. By inhibiting the NF-kappa B pathway, EPIC-1027 disrupts the EGFRvIII-MUC1-C positive feedback loop, inhibits glioma progression, and increases sensitivity to TMZ.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Oncology
Youri Hoogstrate, Santoesha A. Ghisai, Maurice de Wit, Iris de Heer, Kaspar Draaisma, Job van Riet, Harmen J. G. van de Werken, Vincent Bours, Jan Buter, Isabelle Vanden Bempt, Marica Eoli, Enrico Franceschi, Jean-Sebastien Frenel, Thierry Gorlia, Monique C. Hanse, Ann Hoeben, Melissa Kerkhof, Johan M. Kros, Sieger Leenstra, Giuseppe Lombardi, Slavka Lukacova, Pierre A. Robe, Juan M. Sepulveda, Walter Taal, Martin Taphoorn, Rene M. Vernhout, Annemiek M. E. Walenkamp, Colin Watts, Michael Weller, Filip Y. F. de Vos, Guido W. Jenster, Martin van den Bent, Pim J. French
Summary: This study investigated the role of EGFRvIII in glioblastoma using multiple datasets. The results showed significant variations in EGFRvIII expression ratios among tumors. EGFRvIII expression was inversely correlated with pan-EGFR expression and exhibited higher potency in downstream pathway activation. Glioblastomas with EGFRvIII had a lower incidence of CDK4 or MDM2 amplification compared to EGFRvIII-negative tumors.
Article
Biochemistry & Molecular Biology
Adrianna Rutkowska, Tadeusz Strozik, Krystyna Jedrychowska-Danska, Alicja Zamerska, Dorota Jesionek-Kupnicka, Tamara Kowalczyk, Waldemar Och, Blazej Szostak, Cezary Treda, Aneta Wlodarczyk, Amelia Kierasinska-Kalka, Tomasz Wasiak, Damian Ciunowicz, Piotr Rieske, Ewelina Stoczynska-Fidelus
Summary: This study evaluates the use of the L8A4 antibody in detecting EGFRvIII and compares it with other methods. The results indicate that Real-time PCR is a highly specific and sensitive method, and L8A4 antibody shows certain specificity in immunocytochemistry.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Alan T. Yeo, Hyun Jung Jun, Vicky A. Appleman, Piyan Zhang, Hemant Varma, Jann N. Sarkaria, Al Charest
Summary: EGFRvIII plays a crucial role in GBM, relying on co-stimulatory signaling from PDGFRA. The use of kinase inhibitors in combination can effectively suppress EGFRvIII-expressing GBM.
Article
Biochemistry & Molecular Biology
Hee-Jin Kim, Jeong-Yub Kim, Chan-Woong Jung, Young-Sun Lee, Joon-Yong An, Eun Ho Kim, Ki-Hong Kim, Sang Pyung Lee, Jae-Yong Park, Myung-Jin Park
Summary: ANO1 interacts with EGFRvIII, increases its protein stability, and supports the maintenance of stemness and tumor progression in GSCs; knockdown of ANO1 can suppress self-renewal and invasion activities in GSCs.
Article
Oncology
Joseph S. Durgin, Fraser Henderson, MacLean P. Nasrallah, Suyash Mohan, Sumei Wang, Simon F. Lacey, Jan Joseph Melenhorst, Arati S. Desai, John Y. K. Lee, Marcela Maus, Carl H. June, Steven Brem, Roddy S. O'Connor, Zev Binder, Donald M. O'Rourke
Summary: CAR T-EGFRvIII cells have shown promising results in treating patients with IDH1 wildtype recurrent glioblastoma, with one patient surviving 36 months after disease recurrence. Histopathologic analysis revealed immunosuppressive changes in tumor tissue post-infusion, along with decreased EGFRvIII expression. Serial brain imaging demonstrated reduced rCBV after CAR T treatment, suggesting potential efficacy in recurrent GBM patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Virology
Irene Appolloni, Francesco Alessandrini, Laura Menotti, Elisa Avitabile, Daniela Marubbi, Noemi Piga, Davide Ceresa, Francesca Piaggio, Gabriella Campadelli-Fiume, Paolo Malatesta
Summary: R-613, an oncolytic HSV fully retargeted to EGFRvIII, showed promising efficacy in increasing the median survival time of mice with EGFRvIII-expressing human glioblastoma. However, its effectiveness as a late treatment for established glioblastomas was less significant. The susceptibility of uninfected tumor cells to R-613 infection suggests that multiple treatments could enhance its therapeutic efficacy.
Article
Multidisciplinary Sciences
Xuehua Zhang, Guoyan Wang, Yujiao Gong, Leilei Zhao, Ping Song, He Zhang, Yurui Zhang, Huanyu Ju, Xiaoyu Wang, Bin Wang, Huan Ren, Xiao Zhu, Yucui Dong
Summary: The interaction between TGF-beta and EGFRvIII induces the expression and secretion of IGFBP3, promoting the development of GBM. Blocking IGFBP3 may be an additional target in the therapeutic strategy for EGFRvIII-expressing GBM.
Article
Oncology
Raffaella Iurlaro, Inja Waldhauer, Ester Planas-Rigol, Ester Bonfill-Teixidor, Alexandra Arias, Valeria Nicolini, Anne Freimoser-Grundschober, Isabel Cuartas, Alba Martinez-Moreno, Francisco Martinez-Ricarte, Esteban Cordero, Marta Cicuendez, Simona Casalino, Xavier Guardia-Reyes, Linda Fahrni, Thomas Poschinger, Virginie Steinhart, Marine Richard, Stefanie Briner, Joerg Mueller, Franz Osl, Johannes Sam, Sara Colombetti, Marina Bacac, Christian Klein, Estela Pineda, Luis Reyes-Figueroa, Alberto Di Somma, Josep Gonzalez, Paolo Nuciforo, Joan Carles, Maria Vieito, Josep Tabernero, Pablo Umana, Joan Seoane
Summary: T-cell bispecific antibodies (TCB) are engineered molecules that can bind both the T-cell receptor and tumor-specific antigens, showing potential therapeutic effects for EGFRvIII mutation in glioblastoma (GBM). We designed and developed a novel EGFRvIII-TCB with specificity and potent antitumor activity, promoting T-cell activation and cytokine secretion for tumor cell killing, as well as T-cell recruitment into tumors. In GBM animal models, including humanized orthotopic patient-derived xenograft models, EGFRvIII-TCB induced tumor regression. These results support the clinical testing of EGFRvIII-TCB.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Rana Rahmani, Jafar Kiani, Wing Yin Tong, Masoud Soleimani, Nicolas H. H. Voelcker, Ehsan Arefian
Summary: Engineered exosomes targeting GBM cells by carrying two gene therapy agents can significantly improve the apoptosis rate.
JOURNAL OF DRUG TARGETING
(2023)
Meeting Abstract
Oncology
Jennifer L. Guerriero, Gregory J. Baker, Jia-Ren Lin, Yu-An Chen, Ricardo Pastorello, Tuulia Vallius, Janae Davis, Clarence Yapp, Sarah E. Church, Eric Miller, Anniina Farkkila, Shaveta Vinayak, Melinda L. Telli, Giulia Fulci, Alan D'Andrea, Geoffrey I. Shapiro, Sara M. Tolaney, Sandro Santagata, Peter K. Sorger, Elizabeth A. Mittendorf
Article
Oncology
Joseph W. Kim, Rana R. McKay, Marc R. Radke, Shilin Zhao, Mary-Ellen Taplin, Nancy B. Davis, Paul Monk, Leonard J. Appleman, Primo N. Lara, Ulka N. Vaishampayan, Jingsong Zhang, Asit K. Paul, Glenn Bubley, Eliezer M. Van Allen, Serhan Unlu, Ying Huang, Massimo Loda, Geoffrey I. Shapiro, Peter M. Glazer, Patricia M. LoRusso, S. Percy Ivy, Yu Shyr, Elizabeth M. Swisher, Daniel P. Petrylak
Summary: The study investigated the clinical outcomes of combining Cediranib with olaparib in patients with prostate cancer. The results showed that the combination improved radiographic progression-free survival in patients with metastatic castration-resistant prostate cancer compared to olaparib alone. However, it was also associated with a higher incidence of adverse events.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Alexandre Andre B. A. da Costa, Dipanjan Chowdhury, Geoffrey I. Shapiro, Alan D. D'Andrea, Panagiotis A. Konstantinopoulos
Summary: Replication stress is a major cause of genomic instability and a vulnerability of cancer cells. Inhibiting kinases such as ATR, CHK1, WEE1, and MYT1 can target this vulnerability. In addition, inhibiting the DNA damage response can elicit an immune response. Therefore, several inhibitors are being evaluated in clinical trials to overcome therapeutic resistance and promote antitumor immunity by targeting replication stress.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Oncology
Giuseppe Curigliano, Geoffrey Shapiro, Rebecca S. Kristeleit, Albiruni R. Abdul Razak, Stephen Leong, Maria Alsina, Antonio Giordano, Karen A. Gelmon, Erica Stringer-Reasor, Ulka N. Vaishampayan, Mark Middleton, Anthony J. Olszanski, Hope S. Rugo, Kenneth A. Kern, Nuzhat Pathan, Rachelle Perea, Kristen J. Pierce, Sarah C. Mutka, Zev A. Wainberg
Summary: This study evaluated the efficacy and safety of gedatolisib in combination with other anti-tumour agents in advanced solid tumours. The results showed that the combination therapy of gedatolisib and cisplatin had good clinical activity and acceptable tolerability profile in patients with triple-negative breast cancer, both in first-line and second/third-line settings.
BRITISH JOURNAL OF CANCER
(2023)
Correction
Oncology
Giuseppe Curigliano, Geoffrey I. I. Shapiro, Rebecca S. S. Kristeleit, Albiruni R. R. Abdul Razak, Stephen Leong, Maria Alsina, Antonio Giordano, Karen A. A. Gelmon, Erica Stringer-Reasor, Ulka N. N. Vaishampayan, Mark Middleton, Anthony J. J. Olszanski, Hope S. S. Rugo, Kenneth A. A. Kern, Nuzhat Pathan, Rachelle Perea, Kristen J. J. Pierce, Sarah C. C. Mutka, Zev A. A. Wainberg
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Funda Meric-Bernstam, James M. Ford, Peter J. O'Dwyer, Geoffrey I. Shapiro, Lisa M. McShane, Boris Freidlin, Roisin E. O'Cearbhaill, Suzanne George, Julia Glade-Bender, Gary H. Lyman, James Tricoli, David Patton, Stanley R. Hamilton, Robert J. Gray, Douglas S. Hawkins, Bhanumati Ramineni, Keith T. Flaherty, Petros Grivas, Timothy A. Yap, Jordan Berlin, James H. Doroshow, Lyndsay N. Harris, Jeffrey A. Moscow
Summary: In the past decade, there have been multiple trials to determine the effectiveness of treating cancer based on specific genomic alterations. However, most patients do not respond to single-agent therapies targeting a single alteration, and drug resistance often develops. To address this, the NCI has developed NCI-ComboMATCH, a study to explore genomically-directed combination therapies and overcome drug resistance.
CLINICAL CANCER RESEARCH
(2023)
Article
Immunology
Lestat R. Ali, Ana C. Garrido-Castro, Patrick J. Lenehan, Naima Bollenrucher, Courtney T. Stump, Michael Dougan, Shom Goel, Geoffrey I. Shapiro, Sara M. Tolaney, Stephanie K. Dougan
Summary: The authors analyzed blood and tumors from breast and ovarian cancer patients treated with PD-1 blockade and CDK4/6 inhibition using single-cell RNA-sequencing and TCR tracking. They found that both therapies enhance T cell effector function and memory. In mouse models of melanoma and breast cancer, the augmentation of the antitumor memory pool by ribociclib boosts the efficacy of subsequent PD-1 blockade, suggesting sequential therapy as a potentially safe and synergistic strategy in patients.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Oncology
Nami Yamashita, Yoshihiro Morimoto, Atsushi Fushimi, Rehan Ahmad, Atrayee Bhattacharya, Tatsuaki Daimon, Naoki Haratake, Yuka Inoue, Satoshi Ishikawa, Masaaki Yamamoto, Tsuyoshi Hata, Sayuri Akiyoshi, Qiang Hu, Tao Liu, Henry Withers, Song Liu, Geoffrey I. Shapiro, Tomoharu Yoshizumi, Mark D. Long, Donald Kufe
Summary: In certain cancer cells, the chromatin remodeling complex SWI/SNF PBAF's subunit polybromo-1 (PBRM1) drives DNA damage resistance and immune evasion through unclear mechanisms. This study found that MUC1-C is necessary for PBRM1 expression in triple-negative breast cancer (TNBC) cells, and the two proteins form a nuclear complex. Transcriptional and chromatin accessibility analysis showed that MUC1-C and PBRM1 increase the expression of STAT1 and IRF1 by enhancing chromatin accessibility on their respective genes, as well as other genes involved in DNA damage resistance and immune evasion.
MOLECULAR CANCER RESEARCH
(2023)
Article
Oncology
Christian Kollmannsberger, Herbert Hurwitz, Lyudmila Bazhenova, Byoung Chul Cho, David Hong, Keunchil Park, Karen L. Reckamp, Sunil Sharma, Hirak Der-Torossian, James G. Christensen, Demiana Faltaos, Diane Potvin, Vanessa Tassell, Richard Chao, Geoffrey Shapiro
Summary: This phase I study determined the maximum tolerated dose, recommended phase II dose, and safety profile of glesatinib in patients with advanced or unresectable solid tumors. The study found that glesatinib had antitumor activity in patients with tumors harboring overexpression or amplification of MET and AXL, as well as MET-activating mutations or rearrangements. Based on the clinical activity, safety, and pharmacokinetic data, SDD 750 mg twice daily was selected as the preferred formulation and dose of glesatinib.
Article
Oncology
Meghan J. Mooradian, James M. Cleary, Anita Giobbie-Hurder, Lancia N. F. Darville, Aparna Parikh, Elizabeth I. Buchbinder, Justine V. Cohen, Donald P. Lawrence, Geoffrey I. Shapiro, Harold Keer, Helen X. X. Chen, Susan Percy Ivy, Keiran S. M. Smalley, John M. Koomen, Ryan J. Sullivan
Summary: This study showed that the combination of HSP90 inhibitor AT13387 with dabrafenib and trametinib was safe and led to modest disease control in heavily pretreated patients with BRAF V600E/K-mutant solid tumors. Further research is needed to identify tumor types and resistance mechanisms that are most sensitive to this approach.
Article
Oncology
David S. Hong, Michael Postow, Bartosz Chmielowski, Ryan Sullivan, Amita Patnaik, Ezra E. W. Cohen, Geoffrey Shapiro, Conor Steuer, Martin Gutierrez, Heather Yeckes-Rodin, Robert Ilaria Jr, Brenda O'Connell, Joanna Peng, Guangbin Peng, Nora Zizlsperger, Anthony Tolcher, Jedd D. Wolchok
Summary: This study evaluated the safety and tolerability of a new antitumor drug, IPI-549, and found that it has good antitumor activity when used in combination with PD-1/PD-L1 inhibitors, and with minimal side effects. Therefore, doses of 30 and 40 mg of IPI-549 were chosen for the next phase of the study.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Elizabeth Pan, Wanling Xie, Archana Ajmera, Arlene Araneta, Christina Jamieson, Edmund Folefac, Arif Hussain, Christos E. Kyriakopoulos, Adam Olson, Mamta Parikh, Rahul Parikh, Biren Saraiya, S. Percy Ivy, Eliezer M. Van Allen, Neal I. Lindeman, Bose S. Kochupurakkal, Geoffrey I. Shapiro, Rana R. McKay
Summary: In this study, the synergy between olaparib and radium-223 in metastatic castration-resistant prostate cancer (mCRPC) was demonstrated. A phase I dose escalation study showed that olaparib can be safely combined with fixed dose radium-223, and early clinical benefit was observed. The recommended dose of olaparib was 200 mg orally twice daily with radium-223, which will be further investigated in a phase II study.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
James J. Harding, Sarina A. Piha-Paul, Ronak H. H. Shah, Jessica J. Murphy, James M. Cleary, Geoffrey I. Shapiro, David I. Quinn, Irene Brana, Victor Moreno, Mitesh Borad, Sherene Loi, Iben Spanggaard, Haeseong Park, James M. Ford, Monica Arnedos, Salomon M. Stemmer, Christelle de la Fouchardiere, Christos Fountzilas, Jie Zhang, Daniel DiPrimeo, Casey Savin, S. Duygu Selcuklu, Michael F. Berger, Lisa D. Eli, Funda Meric-Bernstam, Komal Jhaveri, David B. Solit, Ghassan K. Abou-Alfa
Summary: In patients with biliary tract cancer, HER2 alterations correlate with poor prognosis. A phase II clinical trial showed that the tyrosine kinase inhibitor neratinib has some efficacy in treating advanced biliary tract cancers with HER2-mutation positive. The objective response rate to neratinib was 16% (95% CI 4.5-36.1%).
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Zahra Talebi, Dominique A. Garrison, Eric D. Eisenmann, Kalindi Parmar, Geoffrey I. Shapiro, Michelle A. Rudek, Alex Sparreboom, Yan Jin
Summary: A rapid, sensitive, and simple UHPLC-MS/MS method was developed and validated for the determination of the PARP inhibitor talazoparib in mouse plasma. The method showed good accuracy and reproducibility, making it suitable for pharmacokinetic studies.
Meeting Abstract
Oncology
Timothy A. Yap, David S. Tan, Anastasios Stathis, Geoffrey I. Shapiro, Satoru Iwasa, Markus Joerger, Jingsong Zhang, Ruth Plummer, Michael Sawyer, Aaron C. Tan, Vincent Castonguay, Nashat Gabrail, Nobuaki Matsubara, Gary Wilkinson, Matthias Ludwig, Yinghui Zhou, Claudia Merz, Joseph Hreiki, Neelesh Sharma, Johan Debono