Article
Oncology
Amy K. LeBlanc, Christina N. Mazcko, Aswini Cherukuri, Erika P. Berger, William C. Kisseberth, Megan E. Brown, Susan E. Lana, Kristen Weishaar, Brian K. Flesner, Jeffrey N. Bryan, David M. Vail, Jenna H. Burton, Jennifer L. Willcox, Anthony J. Mutsaers, J. Paul Woods, Nicole C. Northrup, Corey Saba, Kaitlin M. Curran, Haley Leeper, Heather Wilson-Robles, Brandan G. Wustefeld-Janssens, Stephanie Lindley, Annette N. Smith, Nikolaos Dervisis, Shawna Klahn, Mary Lynn Higginbotham, Raelene M. Wouda, Erika Krick, Jennifer A. Mahoney, Cheryl A. London, Lisa G. Barber, Cheryl E. Balkman, Angela L. McCleary-Wheeler, Steven E. Suter, Olya Martin, Antonella Borgatti, Kristine Burgess, Michael O. Childress, Janean L. Fidel, Sara D. Allstadt, Daniel L. Gustafson, Laura E. Selmic, Chand Khanna, Timothy M. Fan
Summary: Using sirolimus as an mTOR inhibitor in treating appendicular osteosarcoma in pet dogs did not extend disease-free interval or survival.
CLINICAL CANCER RESEARCH
(2021)
Review
Immunology
Anne E. O'Shea, Franklin A. Valdera, Daniel Ensley, Todd R. Smolinsky, Jessica L. Cindass, Phillip M. Kemp Bohan, Annelies T. Hickerson, Elizabeth L. Carpenter, Patrick M. McCarthy, Alexandra M. Adams, Timothy J. Vreeland, Guy T. Clifton, George E. Peoples
Summary: Rapamycin inhibits mTOR signaling, exhibiting both immunosuppressive and immunostimulatory effects on innate and adaptive immune responses. The dose and administration schedule play a crucial role in modulating rapamycin's immunologic effects.
CLINICAL IMMUNOLOGY
(2022)
Article
Oncology
Andrew J. Wagner, Vinod Ravi, Richard F. Riedel, Kristen Ganjoo, Brian A. Van Tine, Rashmi Chugh, Lee Cranmer, Erlinda M. Gordon, Jason L. Hornick, Heng Du, Berta Grigorian, Anita N. Schmid, Shihe Hou, Katherine Harris, David J. Kwiatkowski, Neil P. Desai, Mark A. Dickson
Summary: The study evaluated the efficacy and safety of nab-sirolimus in patients with malignant PEComa, showing an overall response rate of 39% with rapid and durable responses. Patients with TSC2 mutations were more likely to achieve a positive response. nab-sirolimus was considered an important new treatment option for this disease based on response rate, disease control, and safety profile.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Elise F. F. Nassif, Cissimol P. P. Joseph, Rossana Lazcano, Jocelyn T. T. Joseph, Prapassorn Thirasastr, Alexander J. J. Lazar, Neeta Somaiah
Summary: TSC-mutated sarcomas are rare types of sarcoma that are sensitive to mTOR inhibitors. Nab-sirolimus, an albumin-bound mTOR inhibitor, is currently the only FDA-approved treatment for tumors with TSC mutation. We report two cases where patients with TSC-mutated sarcomas responded well to the combination of gemcitabine and sirolimus after prior treatment with gemcitabine-based chemotherapy and nab-sirolimus. This combination could be a viable therapeutic option for patients who have failed nab-sirolimus treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Dermatology
A. J. Duran-Romero, J. C. Hernandez-Rodriguez, J. Ortiz-Alvarez, J. J. Dominguez-Cruz, M. T. Monserrat-Garcia, J. Conejo-Mir Sanchez, J. Bernabeu-Wittel
Summary: Oral sirolimus shows good efficacy and safety in treating high-flow vascular malformations, with most patients experiencing partial relief and tolerating the treatment well. It can be a useful option for long-term stabilization of patients with high-flow vascular malformations.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lucia Lisi, Michela Pizzoferrato, Gabriella Maria Pia Ciotti, Maria Martire, Pierluigi Navarra
Summary: Initially used as immunosuppressants in therapy, selective inhibitors of mTORC1 have now been approved for the treatment of solid tumors. Non-selective mTOR inhibitors are being developed in preclinical and clinical studies in oncology to overcome limitations of selective inhibitors, such as tumor resistance. In this study, we compared the effects of a non-selective mTOR inhibitor, sapanisertib, with rapamycin in glioblastoma cell lines and microglia, and found overlapping and diverging effects, especially in the activation of tumor-associated microglia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Aigli G. Vakrakou, Anastasia Alexaki, Maria-Evgenia Brinia, Maria Anagnostouli, Leonidas Stefanis, Panos Stathopoulos
Summary: This article summarizes the evidence on the role of mammalian targets of rapamycin (mTOR) complex pathways in multiple sclerosis (MS), including autophagy, inflammasome activation, immune responses, and neuronal toxicity. There is robust evidence that mTOR inhibitors, such as rapamycin, improve the clinical course of MS animal models. New research highlights the effects of mTOR on T cells and myeloid cells, providing insight into MS pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Anastasia V. Poznyak, Vasily N. Sukhorukov, Alexander Zhuravlev, Nikolay A. Orekhov, Vladislav Kalmykov, Alexander N. Orekhov
Summary: Atherosclerosis has been a leading cause of death in developed countries for over a decade. The treatment and prevention of this disease are crucial, but there are still gaps in our understanding of its pathogenesis. The mTOR signaling pathway, although well-studied, continues to reveal new details. Therapeutic strategies associated with rapamycin have shown promise in other diseases, suggesting potential effectiveness in atherosclerosis as well.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Chihiro Hisatsune, Tadayuki Shimada, Akitoshi Miyamoto, Amy Lee, Kanato Yamagata
Summary: Tuberous sclerosis complex (TSC) is a developmental disorder characterized by hamartomas in various organs and is often associated with epilepsy. Research has found that TSC2-deficient neurons exhibit heightened neuronal activity with synchronized Ca2+ spikes, with L-type calcium channels (LTCCs) playing a critical role in this abnormal activity. Targeting LTCCs could be a potential novel approach for treating epilepsy in TSC patients.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Xiang Li, Kuangqi Chen, Zixi Wang, Jiayuan Li, Xiawei Wang, Chen Xie, Jianping Tong, Ye Shen
Summary: Corneal diseases affect millions of people worldwide and current treatments have limitations. Activation of the mTOR signaling pathway is involved in the pathogenesis of various corneal diseases, and inhibition of mTOR with rapamycin has shown promising outcomes, indicating the potential of mTOR as a therapeutic target.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Zhili Deng, Mengting Chen, Yingzi Liu, San Xu, Yuyan Ouyang, Wei Shi, Dan Jian, Ben Wang, Fangfen Liu, Jinmao Li, Qian Shi, Qinqin Peng, Ke Sha, Wenqin Xiao, Tangxiele Liu, Yiya Zhang, Hongbing Zhang, Qian Wang, Lunquan Sun, Hongfu Xie, Ji Li
Summary: The study demonstrates that mTORC1 signaling is hyperactivated in the skin of rosacea patients and mouse model, blocking mTORC1 signaling can alleviate rosacea symptoms, while its hyperactivation can worsen the condition.
EMBO MOLECULAR MEDICINE
(2021)
Review
Cardiac & Cardiovascular Systems
Sebastiano Sciarretta, Maurizio Forte, Giacomo Frati, Junichi Sadoshima
Summary: mTOR integrates various signals in the cardiovascular system, playing both adaptive and maladaptive functions in cardiac development and response to stress. Modulating mTOR may hold promise as a therapeutic strategy for cardiac diseases.
CARDIOVASCULAR RESEARCH
(2022)
Article
Biochemical Research Methods
Luqi Jin, Yu Chen, Chunlan Yan, Xiaoyuan Guo, Tingting Jiang, Ayiding Guli, Xinghui Song, Qun Wan, Qiang Shu, Shiping Ding
Summary: The study shows that mTOR inhibition by rapamycin leads to the activation of CDK1, which further regulates cell cycle progression through the Greatwall-endosulfine complex. The research provides insights into the underlying mechanism of how mTOR influences cell cycle events.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Multidisciplinary Sciences
Douglas R. Wassarman, Kondalarao Bankapalli, Leo J. Pallanck, Kevan M. Shokat
Summary: Mammalian target of rapamycin (mTOR) is a crucial factor in cell growth and metabolism, and its signaling in different tissues affects whole-organism processes. Researchers have developed selecTOR, a chemical-genetic system that restricts the activity of rapamycin analog in specific cell populations, achieving selective mTOR inhibition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Rheumatology
Zhaomin Mao, Ying Tan, Juan Tao, Linlin Li, Hui Wang, Feng Yu, Andras Perl, Minghui Zhao
Summary: This study evaluated the activation of mammalian target of rapamycin (mTOR) in renal tissue of LN patients. The activation of mTORC1/2 was found to be significantly increased in different cell types of LN patients compared to controls, and mTORC1 activation was strongly associated with clinical and pathological indicators of LN. The study also identified mTORC1 activation as a prognostic marker in LN patients.
Article
Hematology
Michael W. Deininger, J. Graeme Hodgson, Neil P. Shah, Jorge E. Cortes, Dong-Wook Kim, Franck E. Nicolini, Moshe Talpaz, Michele Baccarani, Martin C. Mueller, Jin Li, Wendy T. Parker, Stephanie Lustgarten, Tim Clackson, Frank G. Haluska, Francois Guilhot, Hagop M. Kantarjian, Simona Soverini, Andreas Hochhaus, Timothy P. Hughes, Victor M. Rivera, Susan Branford
Article
Oncology
Theresa Baker, Sujata Nerle, Justin Pritchard, Boyang Zhao, Victor M. Rivera, Andrew Garner, Francois Gonzalvez
Article
Hematology
Wendy T. Parker, David T. O. Yeung, Alexandra L. Yeoman, Haley K. Altamura, Bronte A. Jamison, Chani R. Field, J. Graeme Hodgson, Stephanie Lustgarten, Victor M. Rivera, Timothy P. Hughes, Susan Branford
Article
Oncology
Sen Zhang, Rana Anjum, Rachel Squillace, Sara Nadworny, Tianjun Zhou, Jeff Keats, Yaoyu Ning, Scott D. Wardwell, David Miller, Youngchul Song, Lindsey Eichinger, Lauren Moran, Wei-Sheng Huang, Shuangying Liu, Dong Zou, Yihan Wang, Qurish Mohemmad, Hyun Gyung Jang, Emily Ye, Narayana Narasimhan, Frank Wang, Juan Miret, Xiaotian Zhu, Tim Clackson, David Dalgarno, William C. Shakespeare, Victor M. Rivera
CLINICAL CANCER RESEARCH
(2016)
Article
Chemistry, Medicinal
Wei-Sheng Huang, Shuangying Liu, Dong Zou, Mathew Thomas, Yihan Wang, Tianjun Zhou, Jan Romero, Anna Kohlmann, Feng Li, Jiwei Qi, Lisi Cai, Timothy A. Dwight, Yongjin Xu, Rongsong Xu, Rory Dodd, Angela Toms, Lois Parillon, Xiaohui Lu, Rana Anjum, Sen Zhang, Frank Wang, Jeffrey Keats, Scott D. Wardwell, Yaoyu Ning, Qihong Xu, Lauren E. Moran, Qurish K. Mohemmad, Hyun Gyung Jang, Tim Clackson, Narayana I. Narasimhan, Victor M. Rivera, Xiaotian Zhu, David Dalgarno, William C. Shakespeare
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Oncology
Scott N. Gettinger, Lyudmila A. Bazhenova, Corey J. Langer, Ravi Salgia, Kathryn A. Gold, Rafael Rosell, Alice T. Shaw, Glen J. Weiss, Meera Tugnait, Narayana I. Narasimhan, David J. Dorer, David Kerstein, Victor M. Rivera, Timothy Clackson, Frank G. Haluska, David Ross Camidge
Article
Oncology
Jeffrey H. Lipton, Charles Chuah, Agnes Guerci-Bresler, Gianantonio Rosti, David Simpson, Sarit Assouline, Gabriel Etienne, Franck E. Nicolini, Philipp le Coutre, Richard E. Clark, Leif Stenke, David Andorsky, Vivian Oehler, Stephanie Lustgarten, Victor M. Rivera, Timothy Clackson, Frank G. Haluska, Michele Baccarani, Jorge E. Cortes, Francois Guilhot, Andreas Hochhaus, Timothy Hughes, Hagop M. Kantarjian, Neil P. Shah, Moshe Talpaz, Michael W. Deininger
Article
Oncology
Joachim T. Siaw, Haiying Wan, Kathrin Pfeifer, Victor M. Rivera, Jikui Guan, Ruth H. Palmer, Bengt Hallberg
Article
Hematology
Jorge E. Cortes, Dong-Wook Kim, Javier Pinilla-Ibarz, Philipp D. le Coutre, Ronald Paquette, Charles Chuah, Franck E. Nicolini, Jane F. Apperley, H. Jean Khoury, Moshe Talpaz, Daniel J. DeAngelo, Elisabetta Abruzzese, Delphine Rea, Michele Baccarani, Martin C. Mueller, Carlo Gambacorti-Passerini, Stephanie Lustgarten, Victor M. Rivera, Frank G. Haluska, Francois Guilhot, Michael W. Deininger, Andreas Hochhaus, Timothy P. Hughes, Neil P. Shah, Hagop M. Kantarjian
Article
Oncology
Andrew P. Garner, Joseph M. Gozgit, Rana Anjum, Sadanand Vodala, Alexa Schrock, Tianjun Zhou, Cesar Serrano, Grant Eilers, Meijun Zhu, Julia Ketzer, Scott Wardwell, Yaoyu Ning, Youngchul Song, Anna Kohlmann, Frank Wang, Tim Clackson, Michael C. Heinrich, Jonathan A. Fletcher, Sebastian Bauer, Victor M. Rivera
CLINICAL CANCER RESEARCH
(2014)
Article
Oncology
Nicholas J. Short, Hagop Kantarjian, Rashmi Kanagal-Shamanna, Koji Sasaki, Farhad Ravandi, Jorge Cortes, Marina Konopleva, Ghayas C. Issa, Steven M. Kornblau, Guillermo Garcia-Manero, Rebecca Garris, Jake Higgins, Gabriel Pratt, Lindsey N. Williams, Charles C. Valentine, Victor M. Rivera, Justin Pritchard, Jesse J. Salk, Jerald Radich, Elias Jabbour
BLOOD CANCER JOURNAL
(2020)
Article
Oncology
Francois Gonzalvez, Sylvie Vincent, Theresa E. Baker, Alexandra E. Gould, Shuai Li, Scott D. Wardwell, Sara Nadworny, Yaoyu Ning, Sen Zhang, Wei-Sheng Huang, Yongbo Hu, Feng Li, Matthew T. Greenfield, Stephan G. Zech, Biplab Das, Narayana Narasimhan, Tim Clackson, David Dalgarno, William C. Shakespeare, Michael Fitzgerald, Johara Chouitar, Robert J. Griffin, Shengwu Liu, Kwok-Kin Wong, Xiaotian Zhu, Victor M. Rivera
Summary: Mobocertinib is a novel irreversible EGFR TKI specifically designed to target oncogenic variants containing activating EGFRex20ins mutations. Preclinical data demonstrate that mobocertinib inhibits EGFRex-20ins-driven cell lines more potently than approved EGFR TKIs, supporting its ongoing clinical development for the treatment of EGFRex20ins-mutated NSCLC.
Article
Oncology
Han Han, Shuai Li, Ting Chen, Michael Fitzgerald, Shengwu Liu, Chengwei Peng, Kwan Ho Tang, Shougen Cao, Johara Chouitar, Jiansheng Wu, David Peng, Jiehui Deng, Zhendong Gao, Theresa E. Baker, Fei Li, Hua Zhang, Yuanwang Pan, Hailin Ding, Hai Hu, Val Pyon, Cassandra Thakurdin, Eleni Papadopoulos, Sittinon Tang, Francois Gonzalvez, Haiquan Chen, Victor M. Rivera, Rachael Brake, Sylvie Vincent, Kwok-Kin Wong
Summary: This study systematically characterized the potent inhibitory activity of mobocertinib against HER2 exon 20 insertionmutant lung cancer and demonstrated the synergistic effect of combined mobocertinib and T-DM1, providing a strong rationale for clinical investigation.
Article
Oncology
Suzanne George, Margaret von Mehren, Jonathan A. Fletcher, Jichao Sun, Sen Zhang, Justin R. Pritchard, John Graeme Hodgson, David Kerstein, Victor M. Rivera, Frank G. Haluska, Michael C. Heinrich
Summary: The study evaluated the efficacy of ponatinib for advanced gastrointestinal stromal tumors (GIST) and found that ponatinib demonstrated activity, particularly in KIT ex11-positive disease. There was a strong concordance of primary KIT mutations between plasma and tumor. Resistance was associated with the emergence of secondary mutations. Ponatinib was ineffective in patients with KIT exon 9 primary mutations. The safety profile was consistent with previous studies.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Michael W. Schmitt, Justin R. Pritchard, Scott M. Leighow, Bella I. Aminov, Lan Beppu, Daniel S. Kim, J. Graeme Hodgson, Victor M. Rivera, Lawrence A. Loeb, Jerald P. Radich
CLINICAL CANCER RESEARCH
(2018)