👤 JF Hancock

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3
Articles
3
Name variants
Also published as: Mark Hancock, R. E. W. Hancock
articles
F Fadlallah, K Elshiwy, Y Elkeraie +1388 more · 2024 · World Journal of Clinical Oncology · added 2026-04-20
F Fadlallah, K Elshiwy, Y Elkeraie, Z Merjaneh, G Khoudari, MT Sarmini, M Gad, M Al-Husseini, A Saad, RL Siegel, KD Miller, NS Wagle, A Jemal, A Kumar, V Gautam, A Sandhu, K Rawat, A Sharma, L Saha, M Bretthauer, M Løberg, P Wieszczy, M Kalager, L Emilsson, K Garborg, M Rupinski, E Dekker, M Spaander, M Bugajski, Ø Holme, AG Zauber, ND Pilonis, A Mroz, EJ Kuipers, J Shi, MA Hernán, HO Adami, J Regula, G Hoff, MF Kaminski, S Shinji, T Yamada, A Matsuda, H Sonoda, R Ohta, T Iwai, K Takeda, K Yonaga, Y Masuda, H Yoshida, M Zajkowska, B Mroczko, GJ Poston, J Figueras, F Giuliante, G Nuzzo, AF Sobrero, JF Gigot, B Nordlinger, R Adam, T Gruenberger, MA Choti, AJ Bilchik, Cutsem EJ Van, JM Chiang, MI D'Angelica, GJ Chang, AM Kaiser, S Mills, JF Rafferty, WD Buie, JR Monson, MR Weiser, J Rafferty, AE Blackmore, MT Wong, CL Tang, BL Green, HC Marshall, F Collinson, P Quirke, P Guillou, DG Jayne, JM Brown, J Mar, A Anton-Ladislao, O Ibarrondo, A Arrospide, S Lázaro, N Gonzalez, M Bare, D Callejo, M Redondo, JM Quintana, S Kitano, M Inomata, J Mizusawa, H Katayama, M Watanabe, S Yamamoto, M Ito, S Saito, S Fujii, F Konishi, Y Saida, H Hasegawa, T Akagi, K Sugihara, T Yamaguchi, T Masaki, Y Fukunaga, K Murata, M Okajima, Y Moriya, Y Shimada, P Gavriilidis, K Katsanos, K Toritani, J Watanabe, K Nakagawa, Y Suwa, H Suwa, A Ishibe, M Ota, C Kunisaki, I Endo, T Matsuda, Y Sumi, K Yamashita, M Yamamoto, Y Matsuda, S Kanaji, T Oshikiri, T Nakamura, S Suzuki, Y Kakeji, RK Cleary, AM Morris, AL Halverson, KA Mirkin, AS Kulaylat, CS Hollenbeak, E Messaris, S Atallah, B Martin-Perez, M Albert, T deBeche-Adams, G Nassif, L Hunter, S Larach, MX Bjørn, SK Perdawood, Z Shen, Y Ye, Q Xie, K Jiang, S Wang, G Wang, Z Wang, Z Jiang, J Liu, J Zhao, J Li, A Arezzo, MA Bonino, F Ris, L Boni, E Cassinotti, DCC Foo, NF Shum, A Brolese, F Ciarleglio, DS Keller, R Rosati, Nardi P De, U Elmore, Romario U Fumagalli, MD Jafari, A Pigazzi, E Rybakov, M Alekseev, N Vettoretto, R Cirocchi, R Passera, E Forcignanò, M Morino, SH Park, HM Park, KR Baek, HM Ahn, IY Lee, GM Son, FA Vuijk, DE Hilling, JSD Mieog, AL Vahrmeijer, A Hiroishi, T Morimoto, K Horikoshi, Y Nakajima, KL Baglan, RC Frazier, D Yan, RR Huang, AA Martinez, JM Robertson, JG Letschert, JV Lebesque, Boer RW de, AA Hart, H Bartelink, JY Wo, CJ Anker, JB Ashman, NA Bhadkamkar, L Bradfield, DT Chang, J Dorth, J Garcia-Aguilar, D Goff, D Jacqmin, P Kelly, NB Newman, J Olsen, AC Raldow, E Ruiz-Garcia, KB Stitzenberg, CR Jr Thomas, QJ Wu, P Das, V Paroder, TJ Fraum, S Nougaret, I Petkovska, GM Rauch, H Kaur, C Bascoul-Mollevi, S Gourgou, C Borg, PL Etienne, E Rio, E Rullier, B Juzyna, F Castan, T Conroy, RR Bahadoer, EA Dijkstra, Etten B van, CAM Marijnen, H Putter, EM Kranenbarg, AGH Roodvoets, ID Nagtegaal, RGH Beets-Tan, LK Blomqvist, T Fokstuen, Tije AJ Ten, J Capdevila, MP Hendriks, I Edhemovic, A Cervantes, PJ Nilsson, B Glimelius, de Velde CJH van, GAP Hospers, P Goffredo, FF Quezada-Diaz, JJ Smith, A Cercek, CSD Roxburgh, P Strombom, LKF Temple, GM Nash, JG Guillem, PB Paty, R Yaeger, ZK Stadler, K Seier, M Gonen, NH Segal, DL Reidy, A Varghese, J Shia, E Vakiani, AJ Wu, CH Crane, MJ Gollub, LB Saltz, V Vendrely, J Asselineau, P Rouanet, JJ Tuech, A Valverde, Chaisemartin C de, M Rivoire, B Trilling, M Jafari, G Portier, B Meunier, I Sieleznieff, M Bertrand, F Marchal, A Dubois, M Pocard, A Rullier, D Smith, N Frulio, E Frison, Q Denost, CC Fossum, JY Alabbad, LB Romak, CL Hallemeier, MG Haddock, M Huebner, EJ Dozois, DW Larson, J Simpson, JH Scholefield, L Feo, M Polcino, E Vinet, N Joharatnam-Hogan, W Wilson, KK Shiu, GK Fusai, B Davidson, D Hochhauser, J Bridgewater, K Khan, JY Luh, KV Albuquerque, C Cheng, RP Ermoian, N Nabavizadeh, H Parsai, JC Roeske, SE Weiss, RB Wynn, Y Yu, SA Rosenthal, A Hartford, S Gwynne, R Webster, R Adams, S Mukherjee, B Coles, J Staffurth, AC Hartford, JM Galvin, DC Beyer, TJ Eichler, GS Ibbott, B Kavanagh, CJ Schultz, ST Chao, LK Dad, LA Dawson, NB Desai, M Pacella, R Rengan, Y Xiao, KM Yenice, BS Teh, SY Woo, EB Butler, SS Lo, AJ Fakiris, EL Chang, NA Mayr, JZ Wang, L Papiez, RC McGarry, HR Cardenes, RD Timmerman, AB Sharabi, PT Tran, M Lim, CG Drake, TL Deweese, E Lavrova, MD Garrett, YF Wang, C Chin, C Elliston, M Savacool, M Price, LA Kachnic, DP Horowitz, KK Brock, CH Chiang, TY Chao, MY Huang, M Haque, MS Shakil, KM Mahmud, EJ Vaios, J Yan, C Wang, X Jiang, Y Wei, Q Wang, K Cui, X Xu, F Wang, L Zhang, T Mitin, AL Zietman, X Tian, K Liu, Y Hou, J Cheng, J Zhang, Y Hiroshima, H Ishikawa, M Murakami, M Nakamura, S Shimizu, T Enomoto, T Oda, M Mizumoto, K Nakai, T Okumura, H Sakurai, G Kraft, S Yamada, H Takiyama, Y Isozaki, M Shinoto, H Makishima, N Yamamoto, H Tsuji, DK Ebner, T Kamada, EG Chiorean, G Nandakumar, T Fadelu, S Temin, AE Alarcon-Rozas, S Bejarano, AE Croitoru, S Grover, PV Lohar, A Odhiambo, ER Garcia, C Teh, A Rose, B Zaki, MD Chamberlin, Dominguez O Hernandez, S Yilmaz, SR Steele, D Duarte, N Vale, XH You, YH Jiang, Z Fang, F Sun, Y Li, W Wang, ZJ Xia, XZ Wang, HQ Ying, L Xiong, Y Lou, L Wang, NN Baxter, EB Kennedy, E Bergsland, J Berlin, TJ George, S Gill, PJ Gold, A Hantel, L Jones, C Lieu, N Mahmoud, YN You, JA Meyerhardt, WJ Thompson, GA Piazza, H Li, L Liu, J Fetter, B Zhu, G Sperl, D Ahnen, R Pamukcu, BN Islam, DD Browning, M Cruz-Burgos, A Losada-Garcia, CD Cruz-Hernández, SA Cortés-Ramírez, I Camacho-Arroyo, V Gonzalez-Covarrubias, M Morales-Pacheco, SI Trujillo-Bornios, M Rodríguez-Dorantes, P Dent, L Booth, JL Roberts, A Poklepovic, JF Hancock, N Arber, CJ Eagle, J Spicak, I Rácz, P Dite, J Hajer, M Zavoral, MJ Lechuga, P Gerletti, J Tang, RB Rosenstein, K Macdonald, P Bhadra, R Fowler, J Wittes, SD Solomon, B Levin, J Peñarando, A Cañas, LM López-Sánchez, F Conde, S Guil-Luna, V Hernández, C Villar, C Morales-Estévez, la Haba-Rodríguez J de, E Aranda, A Rodríguez-Ariza, RK Phillips, MH Wallace, PM Lynch, E Hawk, GB Gordon, BP Saunders, N Wakabayashi, Y Shen, S Zimmerman, L Godio, M Rodrigues-Bigas, LK Su, J Sherman, G Kelloff, G Steinbach, CA Burke, R Phillips, JS Morris, R Slack, X Wang, S Patterson, FA Sinicrope, MA Rodriguez-Bigas, E Half, S Bulow, A Latchford, S Clark, WA Ross, B Malone, H Hasson, E Richmond, D Fina, L Franchi, R Caruso, I Peluso, GC Naccari, S Bellinvia, R Testi, F Pallone, G Monteleone, A Reinacher-Schick, A Schoeneck, U Graeven, I Schwarte-Waldhoff, W Schmiegel, C Stolfi, J Słoka, M Madej, B Strzalka-Mrozik, AF Slater, JH Choi, JS Yoon, YW Won, BB Park, YY Lee, K Sasaki, NH Tsuno, E Sunami, K Kawai, K Hongo, M Hiyoshi, M Kaneko, K Murono, N Tada, T Nirei, K Takahashi, J Kitayama, M Selvakumaran, RK Amaravadi, IA Vasilevskaya, PJ O'Dwyer, LE Anselmino, MV Baglioni, G Reynoso, VR Rozados, OG Scharovsky, MJ Rico, M Menacho-Márquez, T André, C Boni, L Mounedji-Boudiaf, M Navarro, J Tabernero, T Hickish, C Topham, M Zaninelli, P Clingan, I Tabah-Fisch, Gramont A de, A Bonetti, F Rivera, JP Kuebler, HS Wieand, MJ O'Connell, RE Smith, LH Colangelo, G Yothers, NJ Petrelli, MP Findlay, TE Seay, JN Atkins, JL Zapas, JW Goodwin, L Fehrenbacher, RK Ramanathan, BA Conley, PJ Flynn, G Soori, LK Colman, EA Levine, KS Lanier, N Wolmark, A Figer, M Seymour, M Homerin, A Hmissi, J Cassidy, H Cortes-Funes, G Freyer, D Papamichael, Bail N Le, C Louvet, D Hendler, Braud F de, C Wilson, F Morvan, A Mohammed, NB Janakiram, M Brewer, K Vedala, VE Steele, CV Rao, AR Brás, P Fernandes, T Moreira, J Morales-Sanfrutos, E Sabidó, AMM Antunes, A Valente, A Preto, C Teixeira-Guedes, RG Teixeira, Garcia M Helena, TS Morais, P Florindo, MF Piedade, V Moreno, C Ciudad, V Noe, YT Lee, YJ Tan, CE Oon, VV Padma, Z Koveitypour, F Panahi, M Vakilian, M Peymani, Forootan F Seyed, Esfahani MH Nasr, K Ghaedi, N Valeri, C Dearman, S Rao, D Watkins, N Starling, I Chau, D Cunningham, J Neumann, L Wehweck, S Maatz, J Engel, T Kirchner, A Jung, Y Humblet, S Siena, D Khayat, H Bleiberg, A Santoro, D Bets, M Mueser, A Harstrick, C Verslype, Cutsem E Van, G Fornasier, S Francescon, P Baldo, CH Köhne, E Hitre, J Zaluski, Chien CR Chang, A Makhson, G D'Haens, T Pintér, R Lim, G Bodoky, JK Roh, G Folprecht, P Ruff, C Stroh, S Tejpar, M Schlichting, J Nippgen, P Rougier, I Láng, MP Nowacki, S Cascinu, I Shchepotin, J Maurel, A Zubel, I Celik, F Ciardiello, TS Maughan, RA Adams, CG Smith, AM Meade, MT Seymour, RH Wilson, S Idziaszczyk, R Harris, D Fisher, SL Kenny, E Kay, JK Mitchell, A Madi, B Jasani, MD James, MJ Kennedy, B Claes, D Lambrechts, R Kaplan, JP Cheadle, CJ Allegra, RB Rumble, SR Hamilton, PB Mangu, N Roach, RL Schilsky, VK Morris, AB 3rd Benson, M Cho, KK Ciombor, C Cremolini, A Davis, DA Deming, MG Fakih, S Gholami, TS Hong, I Jaiyesimi, K Klute, H Sanoff, JH Strickler, S White, JA Willis, C Eng, F Petrelli, R Ardito, A Ghidini, A Zaniboni, M Ghidini, S Barni, G Tomasello, L Lo, D Patel, AR Townsend, TJ Price, JY Douillard, R Burkes, M Barugel, J Jassem, I Kocákova, M Błasińska-Morawiec, M Šmakal, JL Canon, M Rother, KS Oliner, M Wolf, J Gansert, TW Kim, A Elme, JO Park, AA Udrea, SY Kim, JB Ahn, RV Valencia, S Krishnan, N Manojlovic, X Guan, C Lofton-Day, AS Jung, E Vrdoljak, D Rossini, A Boccaccino, M Carullo, C Antoniotti, G Dima, P Ciracì, F Marmorino, R Moretto, G Masi, T Liu, S Jiang, X Teng, L Zhong, M Liu, Y Jin, M Dong, Y Zhang, JY Zou, Y Wang, A Dasari, S Lonardi, R Garcia-Carbonero, E Elez, T Yoshino, A Sobrero, J Yao, P García-Alfonso, J Kocsis, Gracian A Cubillo, A Sartore-Bianchi, T Satoh, V Randrian, J Tomasek, G Chong, AS Paulson, T Masuishi, J Jones, T Csőszi, F Ghiringhelli, A Shergill, HS Hochster, J Krauss, A Bassam, M Ducreux, L Faugeras, S Kasper, D Arnold, S Nanda, Z Yang, WR Schelman, M Kania, D Dakowicz, R Bhattacharya, XC Ye, R Wang, X Ling, M McManus, F Fan, D Boulbes, LM Ellis, X Ye, L Xia, J Garcia, HI Hurwitz, AB Sandler, D Miles, RL Coleman, R Deurloo, OL Chinot, H Hurwitz, W Novotny, T Cartwright, J Hainsworth, W Heim, A Baron, S Griffing, E Holmgren, N Ferrara, G Fyfe, B Rogers, R Ross, F Kabbinavar, C Zhang, Y Lv, C Cao, J Lu, B Du, X Yang, Y Cui, Y Guo, R Lakomy, H Prenen, J Prausová, T Macarulla, Hazel GA van, V Moiseyenko, D Ferry, J McKendrick, J Polikoff, A Tellier, R Castan, C Allegra, A Thakur, MR Chorawala, RS Patel, AL Cohn, R Obermannova, TE Ciuleanu, DC Portnoy, A Grothey, P Garcia-Alfonso, K Yamazaki, PR Clingan, L Simms, SC Chang, F Nasroulah, P Ge, N Wan, X Han, X Long, Y Bian, Z Gao, Y Bao, Y Fan, G Chen, P Fu, J Ros, M Rodríguez-Castells, N Saoudi, I Baraibar, F Salva, E Élez, H Wasan, J Desai, F Loupakis, YS Hong, N Steeghs, TK Guren, HT Arkenau, A Gollerkeri, K Maharry, J Christy-Bittel, S Kopetz, DY Oh, YJ Bang, SJ Casak, MN Horiba, M Yuan, SJ Lemery, YL Shen, W Fu, JN Moore, Y Bi, D Auth, N Fesenko, PG Kluetz, R Pazdur, LA Fashoyin-Aje, T Vu, FX Claret, K Ng, C Wu, JM Hubbard, AL Coveler, C Fountzilas, A Kardosh, PM Kasi, HJ Lenz, DL Bajor, F Sanchez, M Stecher, W Feng, TS Bekaii-Saab, J Koury, M Lucero, C Cato, L Chang, J Geiger, D Henry, J Hernandez, F Hung, P Kaur, G Teskey, A Tran, Z Zhang, AS Shimu, HX Wei, Q Li, X Zheng, B Li, J Zheng, DM Pardoll, Y Shiravand, F Khodadadi, SMA Kashani, SR Hosseini-Fard, S Hosseini, H Sadeghirad, R Ladwa, K O'Byrne, A Kulasinghe, JA Seidel, A Otsuka, K Kabashima, HB Jie, Y Lei, N Gildener-Leapman, S Trivedi, T Green, LP Kane, RL Ferris, ME Keir, MJ Butte, GJ Freeman, AH Sharpe, M Wu, Q Huang, Y Xie, X Wu, H Ma, Y Xia, for Colorectal Cancer Immunotherapy, C for DE Research, LA Jr Diaz, BV Jensen, LH Jensen, C Punt, M Benavides, P Gibbs, la Fourchardiere C de, DT Le, WY Zhong, D Fogelman, P Marinello, T Andre, F Hirano, K Kaneko, H Tamura, H Dong, M Ichikawa, C Rietz, DB Flies, JS Lau, G Zhu, K Tamada, L Chen, MJ Overman, R McDermott, JL Leach, MA Morse, A Hill, M Axelson, RA Moss, MV Goldberg, ZA Cao, JM Ledeine, GA Maglinte, O Kooshkaki, A Derakhshani, N Hosseinkhani, M Torabi, S Safaei, O Brunetti, V Racanelli, N Silvestris, B Baradaran, V Singh, A Sheikh, MAS Abourehab, P Kesharwani, A GSK, M Lumish, J Sinopoli, J Weiss, M Lamendola-Essel, Dika IH El, N Segal, M Shcherba, R Sugarman, Z Stadler, B Rousseau, G Argiles, M Patel, A Desai, M Widmar, K Iyer, N Gianino, C Crane, PB Romesser, EP Pappou, P Paty, M Gollub, KA Schalper, T Watanabe, T Ishino, Y Ueda, J Nagasaki, T Sadahira, H Dansako, M Araki, Y Togashi, S Hashemzadeh, Z Asadzadeh, MA Shadbad, F Rasibonab, H Safarpour, V Jafarlou, AG Solimando, PK Singh, S Najafi, D Javadrashid, A Tarhini, KYM Wong, F Gelsomino, M Aglietta, MB Sawyer, A Hendlisz, B Neyns, S Abdullaev, A Memaj, M Lei, M Dixon, PM Boland, WW Ma, CH June, SR Riddell, TN Schumacher, A Mitra, A Barua, L Huang, S Ganguly, Q Feng, B He, H Du, J Yang, Q Zhang, J Shen, X Huang, M Wang, Y Huang, J Chen, Y Xu, W Zhao, Y Qi, Y Ou, C Qian, DJ Juat, SJ Hachey, J Billimek, Rosario MP Del, EL Nelson, CCW Hughes, JA Zell, E Martinis, C Ricci, C Trevisan, G Tomadini, S Tonon, Z Wu, M Yang, Y Cao, W Jia, T Zhang, H Huang, H Feng, Z Guo, Z Luo, X Ji, X Cheng, R Zhao, E Janssen, B Subtil, la Jara Ortiz F de, HMW Verheul, DVF Tauriello, Therapeutics Tizona, LLC Inc, Sankyo Co Daiichi, SE BioNTech, DS Neel, TG Bivona, A Bardelli, S Corso, A Bertotti, S Hobor, E Valtorta, G Siravegna, E Scala, A Cassingena, D Zecchin, M Apicella, G Migliardi, F Galimi, C Lauricella, C Zanon, T Perera, S Veronese, G Corti, A Amatu, M Gambacorta, M Sausen, VE Velculescu, P Comoglio, L Trusolino, Nicolantonio F Di, S Giordano, A Jahangiri, Lay M De, LM Miller, WS Carbonell, YL Hu, K Lu, MW Tom, J Paquette, TA Tokuyasu, S Tsao, R Marshall, A Perry, KM Bjorgan, MM Chaumeil, SM Ronen, G Bergers, MK Aghi, CJ LaFargue, P Amero, K Noh, LS Mangala, Y Wen, E Bayraktar, S Umamaheswaran, E Stur, SK Dasari, C Ivan, S Pradeep, W Yoo, C Lu, NB Jennings, V Vathipadiekal, W Hu, A Chelariu-Raicu, Z Ku, H Deng, W Xiong, HJ Choi, M Hu, T Kiyama, CA Mao, R Ali-Fehmi, MJ Birrer, N Zhang, G Lopez-Berestein, Franciscis V de, Z An, AK Sood, M Hao, S Hou, W Li, K Li, L Xue, Q Hu, L Zhu, Y Chen, H Sun, C Ju, YL Tang, DD Li, JY Duan, LM Sheng, J Manzi, CO Hoff, R Ferreira, A Pimentel, J Datta, AS Livingstone, R Vianna, P Abreu, GM Ramzy, M Norkin, T Koessler, L Voirol, M Tihy, D Hany, T McKee, N Buchs, M Docquier, C Toso, L Rubbia-Brandt, G Bakalli, S Guerrier, J Huelsken, P Nowak-Sliwinska, JD Fumet, A Hoos, AM Eggermont, S Janetzki, FS Hodi, R Ibrahim, A Anderson, R Humphrey, B Blumenstein, L Old, J Wolchok, F Tartari, M Santoni, L Burattini, P Mazzanti, A Onofri, R Berardi, J Zugazagoitia, C Guedes, S Ponce, I Ferrer, S Molina-Pinelo, L Paz-Ares, Velzen MJM van, S Derks, Grieken NCT van, Mohammad N Haj, Laarhoven HWM van, N Huyghe, P Baldin, den Eynde M Van, G Trimaglio, AF Tilkin-Mariamé, V Feliu, F Lauzéral-Vizcaino, M Tosolini, C Valle, M Ayyoub, O Neyrolles, N Vergnolle, Y Rombouts, C Devaud, AD Kostic, E Chun, L Robertson, JN Glickman, CA Gallini, M Michaud, TE Clancy, DC Chung, P Lochhead, GL Hold, EM El-Omar, D Brenner, CS Fuchs, M Meyerson, WS Garrett, LS Pessoa, M Heringer, VP Ferrer, Maghvan P Vaseghi, S Jeibouei, ME Akbari, V Niazi, F Karami, A Rezvani, N Ansarinejad, M Abbasinia, G Sarvari, H Zali, R Talaie, A Dey, S Pathak, S Prasad, AS Zhang, H Zhang, XF Sun, A Banerjee Show less
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000 Show more
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000, accounting for 10% of all cancer deaths worldwide. Accordingly, there is a vast amount of ongoing research aiming to find new and improved treatment modalities for CRC that can potentially increase survival and decrease overall morbidity and mortality. Current management strategies for CRC include surgical procedures for resectable cases, and radiotherapy, chemotherapy, and immunotherapy, in addition to their combination, for non-resectable tumors. Despite these options, CRC remains incurable in 50% of cases. Nonetheless, significant improvements in research techniques have allowed for treatment approaches for CRC to be frequently updated, leading to the availability of new drugs and therapeutic strategies. This review summarizes the most recent therapeutic approaches for CRC, with special emphasis on new strategies that are currently being studied and have great potential to improve the prognosis and lifespan of patients with CRC. Show less
📄 PDF DOI: 10.5306/wjco.v15.i9.1136
review
Tahar Aboulkassim, Xiaohong Tian, Qiang Liu +4 more · 2023 · Cell Reports · Elsevier · added 2026-04-20
NRF2 (nuclear factor erythroid 2-related factor 2) is a master regulator of protective responses in healthy tissues. However, when it is active in tumor cells, it can result in drug resistance. KEAP1, Show more
NRF2 (nuclear factor erythroid 2-related factor 2) is a master regulator of protective responses in healthy tissues. However, when it is active in tumor cells, it can result in drug resistance. KEAP1, the endogenous NRF2 inhibitor, binds NRF2 and redirects it to proteasomal degradation, so the KEAP1/NRF2 interaction is critical for maintaining NRF2 at a basal level. A number of clinically relevant KEAP1 mutations were shown to disrupt this critical KEAP1/NRF2 interaction, leading to elevated NRF2 levels and drug resistance. Here, we describe a small-molecule NRF2 inhibitor, R16, that selectively binds KEAP1 mutants and restores their NRF2-inhibitory function by repairing the disrupted KEAP1/NRF2 interactions. R16 substantially sensitizes KEAP1-mutated tumor cells to cisplatin and gefitinib, but does not do so for wild-type KEAP1 cells, and sensitizes KEAP1 G333C-mutated xenograft to cisplatin. We developed a BRET2-based biosensor system to detect the KEAP1/NRF2 interaction and classify KEAP1 mutations. This strategy would identify drug-resistant KEAP1 somatic mutations in clinical molecular profiling of tumors. Show less
no PDF DOI: 10.1016/j.celrep.2023.113104
anticancer bioinorganic bret2 cancer cisplatin drug resistance drug sensitization gefitinib
S. Trapotsi, G. Drakakis, A. Koutsoukas +1688 more · 2022 · RSC Chemical Biology · Royal Society of Chemistry · added 2026-04-20
S. Trapotsi, G. Drakakis, A. Koutsoukas, I. Cortes–Ciriano, P. Martínez–Alonso, T. E. Malliavin, A. Velazquez-Campoy, S. C. Brewerton, M. J. Bodkin, D. A. Evans, R. C. Glen, J. A. Carrodeguas, A. Bender, S. W. Page, J. E. Maddison, M. R. Trusheim, E. R. Berndt, F. L. Douglas, L. Rovin, C. J. Bailey, G. Zhou, R. Myers, Y. Li, Y. Chen, X. Shen, J. Fenyk-Melody, M. Wu, J. Ventre, T. Doebber, N. Fujii, N. Musi, M. F. Hirshman, L. J. Goodyear, D. E. Moller, I. Bezprozvanny, J. Wu, Q. Li, A. C. Lai, C. M. Crews, J. Downward, F. Ardito, M. Giuliani, D. Perrone, G. Troiano, L. L. Muzio, H. Lodish, A. Berk, S. L. Zipursky, P. Matsudaira, D. Baltimore, J. Darnell, N. Ammeux, B. E. Housden, A. Georgiadis, Y. Hu, N. Perrimon, J. E. Dumont, S. Dremier, I. Pirson, C. Maenhaut, T. Vu, F. X. Claret, H. S. Camp, O. Li, S. C. Wise, Y. H. Hong, C. L. Frankowski, R. Vanbogelen, T. Leff, K. Kores, J. Konc, U. Bren, M.-A. Trapotsi, L. H. Mervin, A. M. Afzal, N. Sturm, O. Engkvist, I. P. Barrett, B. Baillif, J. Wichard, O. Méndez-Lucio, D. Rouquié, J. Inglese, D. S. Auld, B. A. Wetmore, J. F. Wambaugh, S. S. Ferguson, M. A. Sochaski, D. M. Rotroff, K. Freeman, H. J. Clewell III, D. J. Dix, M. E. Andersen, K. A. Houck, B. Allen, R. S. Judson, R. Singh, R. J. Kavlock, A. M. Richard, R. S. Thomas, M. Schenone, V. Dančík, B. K. Wagner, P. A. Clemons, A. Subramanian, R. Narayan, S. M. Corsello, D. D. Peck, T. E. Natoli, X. Lu, J. Gould, J. F. Davis, A. A. Tubelli, J. K. Asiedu, D. L. Lahr, J. E. Hirschman, Z. Liu, M. Donahue, B. Julian, M. Khan, D. Wadden, I. C. Smith, D. Lam, A. Liberzon, C. Toder, M. Bagul, M. Orzechowski, O. M. Enache, F. Piccioni, S. A. Johnson, N. J. Lyons, A. H. Berger, A. F. Shamji, A. N. Brooks, A. Vrcic, C. Flynn, J. Rosains, D. Y. Takeda, R. Hu, D. Davison, J. Lamb, K. Ardlie, L. Hogstrom, P. Greenside, N. S. Gray, S. Silver, X. Wu, W.-N. Zhao, W. Read-Button, S. J. Haggarty, L. V. Ronco, J. S. Boehm, S. L. Schreiber, J. G. Doench, J. A. Bittker, D. E. 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Mäkelä, T. Aittokallio, M. Iwata, R. Sawada, H. Iwata, M. Kotera, Y. Yamanishi, E. Dazert, M. Colombi, T. Boldanova, S. Moes, D. Adametz, L. Quagliata, V. Roth, L. Terracciano, M. H. Heim, P. Jenoe, M. N. Hall, D. Carrella, F. Napolitano, R. Rispoli, M. Miglietta, A. Carissimo, L. Cutillo, F. Sirci, F. Gregoretti, D. Di Bernardo, A. Conesa, S. Beck Show less
The elucidation of a compound's Mechanism of Action (MoA) is a challenging task in the drug discovery process, but it is important in order to rationalise phenotypic findings and to anticipate potenti Show more
The elucidation of a compound's Mechanism of Action (MoA) is a challenging task in the drug discovery process, but it is important in order to rationalise phenotypic findings and to anticipate potential side-effects. Bioinformatic approaches, advances in machine learning techniques and the increasing deposition of high-throughput data in public databases have significantly contributed to recent advances in the field, but it is not straightforward to decide which data and methods are most suitable to use in a given case. In this review, we focus on these methods and data and their applications in generating MoA hypotheses for subsequent experimental validation. We discuss compound-specific data such as -omics, cell morphology and bioactivity data, as well as commonly used supplementary prior knowledge such as network and pathway data, and provide information on databases where this data can be accessed. In terms of methodologies, we discuss both well-established methods (connectivity mapping, pathway enrichment) as well as more developing methods (neural networks and multi-omics integration). Finally, we review case studies where the MoA of a compound was successfully suggested from computational analysis by incorporating multiple data modalities and/or methodologies. Our aim for this review is to provide researchers with insights into the benefits and drawbacks of both the data and methods in terms of level of understanding, biases and interpretation – and to highlight future avenues of investigation which we foresee will improve the field of MoA elucidation, including greater public access to -omics data and methodologies which are capable of data integration. Show less
📄 PDF DOI: 10.1039/d1cb00069a
ML review