Article
Oncology
Venkateshwar Madka, Arielle De La Cruz, Gopal Pathuri, Janani Panneerselvam, Yuting Zhang, Nicole Stratton, Sean Hacking, Niklas K. Finnberg, Howard P. Safran, Shizuko Sei, Elizabeth R. Glaze, Robert Shoemaker, Jennifer Fox, Alexander G. Raufi, Wafik S. El-Deiry, Chinthalapally Rao
Summary: The small molecule ONC201/TIC10 has shown great potential for preventing colorectal cancer (CRC). In a preclinical model representing high-risk familial adenomatous polyposis (FAP) patients, ONC201 demonstrated a strong suppressive effect on the development of intestinal tumors in male and female mice.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
Nicholas R. Liguori, Ashley Sanchez Sevilla Uruchurtu, Leiqing Zhang, Abbas E. Abbas, Young S. Lee, Lanlan Zhou, Christopher G. Azzoli, Wafik S. El-Deiry
Summary: This study investigates the synergistic inhibitory effect of combining ONC201 and lurbinectedin on small cell lung cancer (SCLC) cells. The results demonstrate that this combination therapy effectively kills SCLC cells with low toxicity to healthy cells.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Cell Biology
Annika Dwucet, Maximilian Pruss, Qiyu Cao, Mine Tanriover, Varun V. Prabhu, Joshua E. Allen, Aurelia Peraud, Mike-Andrew Westhoff, Markus D. Siegelin, Christian Rainer Wirtz, Georg Karpel-Massler
Summary: The study demonstrates that the imipridone ONC201/TIC10 has a significant inhibitory effect on the cellular viability of medulloblastoma cells independent of c-myc expression, and this effect is enhanced by glucose starvation. Additionally, the combined treatment with ONC201/TIC10 and the glycolysis inhibitor 2-Deoxyglucose shows a synergistic inhibitory effect on the cellular viability of medulloblastoma cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Artem Mishukov, Irina Odinokova, Ekaterina Mndlyan, Margarita Kobyakova, Serazhutdin Abdullaev, Vitaly Zhalimov, Xenia Glukhova, Vasiliy Galat, Yekaterina Galat, Anatoly Senotov, Roman Fadeev, Artem Artykov, Marine E. Gasparian, Marina Solovieva, Igor Beletsky, Ekhson Holmuhamedov
Summary: ONC201 targets mitochondrial ATP-dependent caseinolytic peptidase P (ClpP) and has reversible and irreversible effects on cancer cells. When used in combination with NK cells, it enhances the anti-cancer effect.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Hao Cui, Zan Hu, Kang Yang, Jingkun Huang, Yichao Wu, Quanwei Chen, Ran Wei, Penfeng Wang, Hui Wang, Hongmei Li, Yadong Chen, Tao Lu, Yuqin Yao, Yong Zhu
Summary: Activation of the TRAIL proapoptotic pathway can promote cancer cell apoptosis. Histone deacetylases (HDACs) are promising drug targets for cancers. The development of highly TRAIL-sensitive HDAC inhibitors that can synergize with TRAIL may be a promising strategy for cancer treatment. Compound IIc showed good inhibitory activity against HDAC1 and HCT116 cells and displayed higher sensitivity than ONC201 in activating TRAIL expression and promoting apoptosis. In a xenograft model, compound IIc exhibited significantly greater inhibitory activity compared to positive control drugs. These findings suggest the potential of highly TRAIL-sensitive HDAC inhibitors as colorectal tumor cancer drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Jyoti M. Honnanayakanavar, Jagadeesh Babu Nanubolu, Surisetti Suresh
Summary: This study presents a novel copper-catalyzed tandem reaction for the efficient synthesis of a specific three-ring compound, which has been successfully applied to the total synthesis of the anticancer drug TIC10/ONC201.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Oncology
Jocelyn E. Ray, Marie D. Ralff, Aakash Jhaveri, Lanlan Zhou, David T. Dicker, Eric A. Ross, Wafik S. El-Deiry
Summary: ONC201 demonstrated promising activity in patients with advanced endometrial cancer by upregulating DR5 and sensitizing tumors to TRAIL. The combination of ONC201 and TRAIL promoted cell death in endometrial cancer models in vitro and in vivo, suggesting a novel cancer therapeutic strategy.
CANCER BIOLOGY & THERAPY
(2021)
Article
Pharmacology & Pharmacy
Eva Fuchs, David Alexander Christian Messerer, Georg Karpel-Massler, Michael Fauler, Thomas Zimmer, Bettina Jungwirth, Karl Josef Foehr
Summary: In addition to its classical anti-cancer activity, the tumor therapeutic drug TIC10 may enhance its anti-tumor properties by blocking voltage-gated sodium channels.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Oliver H. Voss, Daniel Arango, Justin C. Tossey, Miguel A. Villalona Calero, Andrea Doseff
Summary: Apigenin sensitizes primary lung cancer cells to TRAIL-induced apoptosis through reprogramming alternative splicing of key TRAIL/DISC components and directly binding heat shock protein 70 to promote cell death. These findings emphasize the synergies between diet and cancer treatments, providing new avenues for improved cancer therapies.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Simone Oerlemans, Fabio Efficace, Charalampia Kyriakou, Ana Carolina Freitas, Omar Shamieh, Carien L. Creutzberg, Jens Lehmann, Duska Petranovic, Eva Nagele, Anne Bredart, Dong Dong, Christian W. Scholz, Giovanni Caocci, Stefano Molica, Laimonas Griskevicius, Aliki Xochelli, Jacobien M. Kieffer, Joost A. Agelink van Rentergem, Waleed Alrjoub, Anja Mueller, Maria Gomes Da Silva, Filipa Alves da Costa, Sandra Malak, Kim Cocks, Lonneke van de Poll-franse
Summary: This study tested the psychometric properties of two newly developed measures for patients with high-grade and low-grade non-Hodgkin lymphoma, and found that the questionnaires are reliable and valid. They can now be used in clinical research and practice to better inform treatment decision-making.
Article
Cell Biology
Emir Bozkurt, Heiko Dussmann, Manuela Salvucci, Brenton L. Cavanagh, Sandra Van Schaeybroeck, Daniel B. Longley, Seamus J. Martin, Jochen H. M. Prehn
Summary: The study reveals that TRAIL signaling not only activates apoptosis in colon cancer cells but also induces entosis through TRAIL receptors and the structural presence of caspase-8. The association of TRAIL signaling with cell-in-cell structures is significant in colorectal cancer, especially in the context of patient prognosis. Factors controlling entosis in tumors remain to be elucidated despite the evidence of entosis in cancers.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Anderson Luiz-Ferreira, Teresa Pacifico, Alefe Cardoso Cruz, Federica Laudisi, Giovanni Monteleone, Carmine Stolfi
Summary: TRAIL is a promising anticancer agent that selectively induces apoptosis in transformed cells, while flavonoids, natural compounds found in plants, have shown competence in enhancing TRAIL-induced apoptosis. However, bioavailability issues are the main limitations for the clinical use of flavonoids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Anna-Christina Rambow, Insa Aschenbach, Sofie Hagelund, Doaa Tawfik, Jan-Paul Gundlach, Sebastian Weisse, Nicolai Maass, Anna Trauzold
Summary: Binding of TRAIL to its death domain-containing receptors TRAIL-R1 and TRAIL-R2 can induce cell death and/or pro-inflammatory signaling. The importance of TRAIL and TRAIL-R1/R2 in tumor immune surveillance and cancer biology has meanwhile been well documented. TRAIL also binds to TRAIL-R3 and TRAIL-R4, which have regulatory functions in apoptotic and non-apoptotic signaling pathways. Knockdown of TRAIL-R4 affects the activation of apoptotic and non-apoptotic pathways in cancer cells, showing opposing effects on cell death and clonogenic survival. TRAIL-R4 also regulates the expression of anti-apoptotic proteins and affects the activity of AKT, ERK, p38 and NF-kappa B. This study provides evidence for the important role of endogenous TRAIL-R4 in cancer cells and improves the understanding of the complex TRAIL/TRAIL-R system in humans.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Francesca R. Di Cristofano, Mara W. Fong, Kelsey E. Huntington, Benedito A. Carneiro, Lanlan Zhou, Wafik S. El-Deiry
Summary: The combination of ONC201 and ABT-263 shows strong synergistic effects in inducing tumor cell death and altering cell death mediators. It is not toxic to human fibroblast cells and holds promise for further exploration in vivo and in clinical trials against various solid malignancies.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Bora Lim, Christine B. Peterson, Alexander Davis, Elin Cho, Troy Pearson, Huey Liu, Minha Hwang, Naoto Tada Ueno, Jangsoon Lee
Summary: The study showed that a combination therapy of ONC201 with MEK inhibitor can effectively inhibit the growth of triple-negative breast cancer cell lines, with ClpP levels correlating with ONC201 efficacy. Three-dimensional RNA interference screening identified MAPK and PI3K/Akt pathways as potential synergistic therapeutic partners.
Article
Oncology
Emmanuel K. Teye, Abigail Sido, Ping Xin, Niklas K. Finnberg, Prashanth Gokare, Yuka I. Kawasawa, Anna C. Salzberg, Sara Shimko, Michael Bayerl, W. Christopher Ehmann, David F. Claxton, Witold B. Rybka, Joseph J. Drabick, Hong-Gang Wang, Thomas Abraham, Wafik S. El-Deiry, Robert A. Brodsky, Raymond J. Hohl, Jeffrey J. Pu
Letter
Oncology
Liz J. Hernandez Borrero, Rahmat Sikder, Amriti Lulla, Prashanth Gokare, Paulo R. Del Valle, Xiaobing Tian, Shengliang Zhang, Philip H. Abbosh, Wafik S. El-Deiry
Article
Cell Biology
Liz J. Hernandez-Borrero, Shengliang Zhang, Amriti Lulla, David T. Dicker, Wafik S. El-Deiry
Article
Cell Biology
Varun V. Prabhu, Mala K. Talekar, Amriti R. Lulla, C. Leah B. Kline, Lanlan Zhou, Junior Hall, A. Pieter J. Van den Heuvel, David T. Dicker, Jawad Babar, Stephan A. Grupp, Mathew J. Garnett, Ultan McDermott, Cyril H. Benes, Jeffrey J. Pu, David F. Claxton, Nadia Khan, Wolfgang Oster, Joshua E. Allen, Wafik S. El-Deiry
Review
Biochemistry & Molecular Biology
Lorenzo Galluzzi, Ilio Vitale, Stuart A. Aaronson, John M. Abrams, Dieter Adam, Patrizia Agostinis, Emad S. Alnemri, Lucia Altucci, Ivano Amelio, David W. Andrews, Margherita Annicchiarico-Petruzzelli, Alexey V. Antonov, Eli Arama, Eric H. Baehrecke, Nickolai A. Barlev, Nicolas G. Bazan, Francesca Bernassola, Mathieu J. M. Bertrand, Katiuscia Bianchi, Mikhail V. Blagosklonny, Klas Blomgren, Christoph Borner, Patricia Boya, Catherine Brenner, Michelangelo Campanella, Eleonora Candi, Didac Carmona-Gutierrez, Francesco Cecconi, Francis K. -M. Chan, Navdeep S. Chandel, Emily H. Cheng, Jerry E. Chipuk, John A. Cidlowski, Aaron Ciechanover, Gerald M. Cohen, Marcus Conrad, Juan R. Cubillos-Ruiz, Peter E. Czabotar, Vincenzo D'Angiolella, Ted M. Dawson, Valina L. Dawson, Vincenzo De laurenzi, Ruggero De Maria, Klaus-Michael Debatin, Ralph J. DeBerardinis, Mohanish Deshmukh, Nicola Di Daniele, Francesco Di Virgilio, Vishva M. Dixit, Scott J. Dixon, Colin S. Duckett, Brian D. Dynlacht, Wafik S. El-Deiry, John W. Elrod, Gian Maria Fimia, Simone Fulda, Ana J. Garcia-Saez, Abhishek D. Garg, Carmen Garrido, Evripidis Gavathiotis, Pierre Golstein, Eyal Gottlieb, Douglas R. Green, Lloyd A. Greene, Hinrich Gronemeyer, Atan Gross, Gyorgy Hajnoczky, J. Marie Hardwick, Isaac S. Harris, Michael O. Hengartner, Claudio Hetz, Hidenori Ichijo, Marja Jaattela, Bertrand Joseph, Philipp J. Jost, Philippe P. Juin, William J. Kaiser, Michael Karin, Thomas Kaufmann, Oliver Kepp, Adi Kimchi, Richard N. Kitsis, Daniel J. Klionsky, Richard A. Knight, Sharad Kumar, Sam W. Lee, John J. Lemasters, Beth Levine, Andreas Linkermann, Stuart A. Lipton, Richard A. Lockshin, Carlos Lopez-Otin, Scott W. Lowe, Tom Luedde, Enrico Lugli, Marion MacFarlane, Frank Madeo, Michal Malewicz, Walter Malorni, Gwenola Manic, Jean-Christophe Marine, Seamus J. Martin, Jean-Claude Martinou, Jan Paul Medema, Patrick Mehlen, Pascal Meier, Sonia Melino, Edward A. Miao, Jeffery D. Molkentin, Ute M. Moll, Cristina Munoz-Pinedo, Shigekazu Nagata, Gabriel Nunez, Andrew Oberst, Moshe Oren, Michael Overholtzer, Michele Pagano, Theocharis Panaretakis, Manolis Pasparakis, Josef M. Penninger, David M. Pereira, Shazib Pervaiz, Marcus E. Peter, Mauro Piacentini, Paolo Pinton, Jochen H. M. Prehn, Hamsa Puthalakath, Gabriel A. Rabinovich, Markus Rehm, Rosario Rizzuto, Cecilia M. P. Rodrigues, David C. Rubinsztein, Thomas Rudel, Kevin M. Ryan, Emre Sayan, Luca Scorrano, Feng Shao, Yufang Shi, John Silke, Hans-Uwe Simon, Antonella Sistigu, Brent R. Stockwell, Andreas Strasser, Gyorgy Szabadkai, Stephen W. G. Tait, Daolin Tang, Nektarios Tavernarakis, Andrew Thorburn, Yoshihide Tsujimoto, Boris Turk, Tom Vanden Berghe, Peter Vandenabeele, Matthew G. Vander Heiden, Andreas Villunger, Herbert W. Virgin, Karen H. Vousden, Domagoj Vucic, Erwin F. Wagner, Henning Walczak, David Wallach, Ying Wang, James A. Wells, Will Wood, Junying Yuan, Zahra Zakeri, Boris Zhivotovsky, Laurence Zitvogel, Gerry Melino, Guido Kroemer
CELL DEATH AND DIFFERENTIATION
(2018)
Article
Medicine, Research & Experimental
Jessica Wagner, C. Leah Kline, Lanlan Zhou, Kerry S. Campbell, Alexander W. MacFarlane, Anthony J. Olszanski, Kathy Q. Cai, Harvey H. Hensley, Eric A. Ross, Marie D. Ralff, Andrew Zloza, Charles B. Chesson, Jenna H. Newman, Howard Kaufman, Joseph Bertino, Mark Stein, Wafik S. El-Deiry
JOURNAL OF CLINICAL INVESTIGATION
(2018)
Article
Oncology
Jessica Wagner, C. Leah Kline, Lanlan Zhou, Vladimir Khazak, Wafik S. El-Deiry
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2018)
Article
Oncology
Avital Lev, Amriti R. Lulla, Brian C. Ross, Marie D. Ralff, Petr B. Makhov, David T. Dicker, Wafik S. El-Deiry
MOLECULAR CANCER RESEARCH
(2018)
Article
Medicine, General & Internal
A. Drilon, T. W. Laetsch, S. Kummar, S. G. DuBois, U. N. Lassen, G. D. Demetri, M. Nathenson, R. C. Doebele, A. F. Farago, A. S. Pappo, B. Turpin, A. Dowlati, M. S. Brose, L. Mascarenhas, N. Federman, J. Berlin, W. S. El-Deiry, C. Baik, J. Deeken, V. Boni, R. Nagasubramanian, M. Taylor, E. R. Rudzinski, F. Meric-Bernstam, D. P. S. Sohal, P. C. Ma, L. E. Raez, J. F. Hechtman, R. Benayed, M. Ladanyi, B. B. Tuch, K. Ebata, S. Cruickshank, N. C. Ku, M. C. Cox, D. S. Hawkins, D. S. Hong, D. M. Hyman
NEW ENGLAND JOURNAL OF MEDICINE
(2018)
Article
Oncology
Elizabeth M. Matthew, Zhaohai Yang, Suraj Peri, Mark Andrake, Roland Dunbrack, Eric Ross, Wafik S. El-Deiry
Article
Oncology
Christina Leah B. Kline, Marie D. Ralff, Amriti R. Lulla, Jessica M. Wagner, Phillip H. Abbosh, David T. Dicker, Joshua E. Allen, Wafik S. El-Deiry
Article
Oncology
Lindsey Carlsen, Kelsey E. Huntington, Wafik S. El-Deiry
Summary: This review discusses preclinical and clinical studies on immunotherapy for colorectal cancer, including various treatment methods and predictive biomarkers for treatment response. Despite certain limitations, immunotherapy provides hope for improving patient outcomes and quality of life.
Review
Biochemistry & Molecular Biology
Shengliang Zhang, Lindsey Carlsen, Liz Hernandez Borrero, Attila A. Seyhan, Xiaobing Tian, Wafik S. El-Deiry
Summary: This article summarizes the current progress in targeting wild-type and mutant p53 for cancer therapy using biotherapeutic and biopharmaceutical methods. Strategies include boosting p53 activity, restoring p53 pathway function, targeting p53 in immunotherapy, and combination therapies.
Review
Biochemistry & Molecular Biology
Lindsey Carlsen, Wafik S. El-Deiry
Summary: The TP53 gene, encoding the tumor suppressor protein p53, is mutated in around 50% of cancers. After DNA damage, p53 acts as a transcription factor to activate target genes for cell fates such as apoptosis, cell cycle arrest, and DNA repair. The complex regulatory network controlling target gene selection by p53 varies across contexts such as treatment type, cell type, and tissue type.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)