đŸ‘€ JH Lamb

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Also published as: J. Lamb, R Lamb
articles
PN Beerkens, J Bussink, TW Secomb +159 more · 2024 · Cancer & Metabolism · BioMed Central · added 2026-04-20
PN Beerkens, J Bussink, TW Secomb, R Hsu, ET Ong, JF Gross, MW Dewhirst, JM Brown, DF Boreel, PN Span, S Heskamp, GJ Adema, SE Rademakers, JH Kaanders, FC Sweep, AJ van der Kogel, MC Joiner, DR Grimes, M Partridge, JT Coates, M Skwarski, GS Higgins, US Gaipl, G Multhoff, H Scheithauer, K Lauber, S Hehlgans, B Frey, TM Ashton, E Fokas, LA Kunz-Schughart, LK Folkes, S Anbalagan, M Huether, KTY Han, A Fyles, T Shek, J Croke, N Dhani, D D’Souza, DR McGowan, E Belcher, F Di Chiara, D Stavroulias, M McCole, TA Yap, N Daver, M Mahendra, J Zhang, C Kamiya-Matsuoka, F Meric-Bernstam, F Janku, P LoRusso, AS Mansfield, R Nanda, A Spira, T Wang, G Cheng, M Hardy, P Topchyan, R Zander, P Volberding, W Cui, J Zielonka, O Ouari, M Lopez, D McAllister, K Boyle, J Joseph, A Sikora, J Vasquez-Vivar, IC Summerhayes, TJ Lampidis, SD Bernal, JJ Nadakavukaren, KK Nadakavukaren, EL Shepherd, JS Modica-Napolitano, JR Aprille, FM Veronese, G Pasut, M Busk, J Overgaard, MR Horsman, J Lok, SP Burr, AS Costa, GL Grice, RT Timms, IT Lobb, P Freisinger, LD Falo, M Kovacsovics-Bankowski, K Thompson, KL Rock, K Rohlenova, K Sachaphibulkij, J Stursa, A Bezawork-Geleta, J Blecha, B Endaya, Z Bielcikova, L Krizova, L Dong, J Spacek, S Hlousek, A Nagelkerke, FCGJ Sweep, JM Newton, A Hanoteau, HC Liu, A Gaspero, F Parikh, RD Gartrell-Corrado, JM Henk, PB Kunkler, CW Smith, GO Janssens, CH Terhaard, PA Doornaert, HP Bijl, P van den Ende, JR Molina, Y Sun, M Protopopova, S Gera, M Bandi, C Bristow, T Lofton, M Smith, CA Bristow, A Carugo, M Benej, X Hong, S Vibhute, S Scott, J Wu, E Graves, S Nadanaciva, A Bernal, R Aggeler, R Capaldi, Y Will, QY Li, Y Huang, M Fiorillo, R Lamb, HB Tanowitz, L Mutti, M Krstic-Demonacos, AR Cappello, M Huang, D Xiong, J Pan, Q Zhang, Y Wang, CR Myers, RP Garay, R El-Gewely, JK Armstrong, G Garratty, P Richette Show less
Background Hypoxia is a common feature of many solid tumors and causes radiotherapy and immunotherapy resistance. Pharmacological inhibition of oxidative phosphorylation (OXPHOS) has emerged as a the Show more
Background Hypoxia is a common feature of many solid tumors and causes radiotherapy and immunotherapy resistance. Pharmacological inhibition of oxidative phosphorylation (OXPHOS) has emerged as a therapeutic strategy to reduce hypoxia. However, the OXPHOS inhibitors tested in clinical trials caused only moderate responses in hypoxia alleviation or trials were terminated due to dose-limiting toxicities. To improve the therapeutic benefit, FDA approved OXPHOS inhibitors (e.g. atovaquone) were conjugated to triphenylphosphonium (TPP + ) to preferentially target cancer cell’s mitochondria. In this study, we evaluated the hypoxia reducing effects of several mitochondria-targeted OXPHOS inhibitors and compared them to non-mitochondria-targeted OXPHOS inhibitors using newly developed spheroid models for diffusion-limited hypoxia. Methods B16OVA murine melanoma cells and MC38 murine colon cancer cells expressing a HIF-Responsive Element (HRE)-induced Green Fluorescent Protein (GFP) with an oxygen-dependent degradation domain (HRE-eGFP-ODD) were generated to assess diffusion-limited hypoxia dynamics in spheroids. Spheroids were treated with IACS-010759, atovaquone, metformin, tamoxifen or with mitochondria-targeted atovaquone (Mito-ATO), PEGylated mitochondria-targeted atovaquone (Mito-PEG-ATO) or mitochondria-targeted tamoxifen (MitoTam). Hypoxia dynamics were followed and quantified over time using the IncuCyte Zoom Live Cell-Imaging system. Results Hypoxic cores developed in B16OVA.HRE and MC38.HRE spheroids within 24 h hours after seeding. Treatment with IACS-010759, metformin, atovaquone, Mito-PEG-ATO and MitoTam showed a dose-dependent reduction of hypoxia in both B16OVA.HRE and MC38.HRE spheroids. Mito-ATO only alleviated hypoxia in MC38.HRE spheroids while tamoxifen was not able to reduce hypoxia in any of the spheroid models. The mitochondria-targeted OXPHOS inhibitors demonstrated stronger anti-hypoxic effects compared to the non-mito-targeted OXPHOS inhibitors. Conclusions We successfully developed a high-throughput spheroid model in which hypoxia dynamics can be quantified over time. Using this model, we showed that the mitochondria-targeted OXPHOS inhibitors Mito-ATO, Mito-PEG-ATO and MitoTam reduce hypoxia in tumor cells in a dose-dependent manner, potentially sensitizing hypoxic tumor cells for radiotherapy. Supplementary Information The online version contains supplementary material available at 10.1186/s40170-024-00342-6. Show less
📄 PDF DOI: 10.1186/s40170-024-00342-6
amino-acid imaging mitochondria
Li Xing, Shaohui Wang, H Sung +944 more · 2023 · Cell Death Discovery · Nature · added 2026-04-20
Li Xing, Shaohui Wang, H Sung, J Ferlay, RL Siegel, M Laversanne, I Soerjomataram, A Jemal, C Xia, X Dong, H Li, M Cao, D Sun, S He, W Cao, HD Chen, YW Yu, N Li, WQ Chen, BC Bade, CS Dela Cruz, AH Nielsen, U Fredberg, F Wu, L Wang, C Zhou, MI Toki, K Harrington, KN Syrigos, R Rosell, N Karachaliou, O Arrieta, RS Herbst, D Morgensztern, C Boshoff, ZF Lim, PC Ma, J Liu, M Hong, Y Li, D Chen, Y Wu, Y Hu, SJ Dixon, KM Lemberg, MR Lamprecht, R Skouta, EM Zaitsev, CE Gleason, J Li, F Cao, HL Yin, ZJ Huang, ZT Lin, N Mao, DH Manz, NL Blanchette, BT Paul, FM Torti, SV Torti, Y Mou, J Wang, J Wu, D He, C Zhang, C Duan, RS Hotchkiss, A Strasser, JE McDunn, PE Swanson, DL Vaux, D Moujalled, JR Liddell, ML Coleman, EA Sahai, M Yeo, M Bosch, A Dewar, MF Olson, M Suzanne, H Steller, X Chen, PB Comish, D Tang, R Kang, JR Hunt, MK Georgieff, IV Milto, IV Suhodolo, VD Prokopieva, TK Klimenteva, DJ Lane, AM Merlot, ML Huang, DH Bae, PJ Jansson, S Sahni, MW Hentze, MU Muckenthaler, B Galy, C Camaschella, D Galaris, A Barbouti, K Pantopoulos, T Nakamura, I Naguro, H Ichijo, C Yu, W Hou, Y Xie, X Song, X Sun, MT Lotze, HJ Zeh, A Donovan, CA Lima, JL Pinkus, GS Pinkus, LI Zon, S Robine, M Kruszewski, HB Dunford, A HamaĂŻ, M Mehrpour, LJ Su, JH Zhang, H Gomez, R Murugan, X Hong, D Xu, S Doll, M Conrad, S Zalba, TL Ten Hagen, MP Wymann, R Schneiter, MM Gaschler, BR Stockwell, D Li, H Kuwata, S Hara, VE Kagan, G Mao, F Qu, JP Angeli, CS Croix, GE Winter, LS Musavi, ED Lee, B Snijder, M Rebsamen, P Vishnupriya, A Aparna, VP Viswanadha, WS Yang, KJ Kim, M Patel, MS Shchepinov, NK Singh, GN Rao, Y Zou, ET Graham, AA Deik, JK Eaton, W Wang, B Yan, Y Ai, Q Sun, Y Ma, Y Cao, H Lv, C Zhen, P Yang, L Hu, P Shang, J Lewerenz, SJ Hewett, Y Huang, M Lambros, PW Gout, PW Kalivas, H Sato, H Imai, M Matsuoka, T Kumagai, T Sakamoto, T Koumura, R SriRamaratnam, ME Welsch, K Shimada, VS Viswanathan, P Koppula, L Zhuang, B Gan, X Wang, Z Huang, Y Zhou, J Xia, W Hu, R Kong, N Wang, W Han, W Bao, J Lu, K Bersuker, JM Hendricks, Z Li, L Magtanong, B Ford, PH Tang, FP Freitas, R Shah, M Aldrovandi, MC da Silva, I Ingold, E Mishima, J Ito, Z Wu, A Wahida, C Mao, X Liu, Y Zhang, G Lei, Y Yan, H Lee, M Soula, RA Weber, O Zilka, H Alwaseem, K La, F Yen, VAN Kraft, CT Bezjian, S Pfeiffer, L Ringelstetter, C MĂŒller, F Zandkarimi, J Vasquez-Vivar, Z Shi, S Tan, R Brigelius-FlohĂ©, C Wang, Z Yang, Y Bai, T Shukuya, ME Poh, J Ni, K Chen, J Zhang, X Zhang, S Sui, L Zhang, S Xu, Z Wang, X Tian, Y Yang, L Ma, X Pan, Z Lin, D Jiang, Y Yu, D Yang, H Zhou, FJ Li, HZ Long, ZW Zhou, HY Luo, SG Xu, LC Gao, Z Fan, G Yang, W Zhang, Q Liu, G Liu, P Liu, L Feng, K Zhao, L Sun, X Yin, C Liu, M Chen, Y Jiang, Y Sun, X Wu, Z Sui, H Zhang, Y Wang, Z Yu, X Ji, J Qian, SMJ Rahman, PJ Siska, BK Harris, L Bai, L Zhi, Q Zhao, Y Chen, H Tian, J Jin, KR Zhang, YF Zhang, HM Lei, YB Tang, CS Ma, QM Lv, Y Xu, D Lv, C Yan, H Su, Y Shi, K Wang, J He, C Tu, H Xu, Y Lv, F He, L Antonucci, M Karin, E Panieri, L Saso, J Yang, Z Zhao, B Cao, S Yu, S Sajadimajd, M Khazaei, Z Ou, R Chen, X Niu, D Wu, J Duan, H Xiao, L Zhao, YP Kang, A Mockabee-Macias, C Jiang, A Falzone, N Prieto-Farigua, E Stone, W Liu, W Duan, J Song, S Wei, S Xia, H Wang, Q Huang, S Cheng, D Pei, B Proneth, YY Tyurina, E Panzilius, S Kobayashi, HL Zhang, BX Hu, ZL Li, T Du, JL Shan, ZP Ye, R Sha, C Yuan, X Sheng, J Peng, S Li, F Li, C Lv, QK Yang, H Wu, A Liu, J Hou, X Wen, C Li, S Xiong, T Yue, X Yang, X Hu, N Guo, YS Guan, Q He, Q Zou, L Yang, W Cui, Y Liu, QR Sun, L Jiang, N Kon, T Li, SJ Wang, T Su, H Hibshoosh, W Gu, G Kroemer, C Huang, M Yang, J Deng, P Li, W Su, R Jiang, W Yang, X He, Z Zhang, X Zheng, KR Marshall, M Gong, L Wodke, JH Lamb, DJ Jones, PB Farmer, L Kondiparthi, A Jo, JH Bae, YJ Yoon, TH Chung, EW Lee, YH Kim, JY Song, J Marszalek, EA Craig, EM Terzi, VO Sviderskiy, SW Alvarez, GC Whiten, R Possemato, T Papagiannakopoulos, AL Moreira, S Adams, KM Fujihara, BZ Zhang, TD Jackson, MO Ogunkola, B Nijagal, JV Milne, X Ye, C Ji, C Cheng, R Tang, J Xu, L Liu, XZ Yu, TS Li, LX Song, PL Chen, TL Suo, P Chen, WM Li, Q Lu, XL Yan, ZP Zhang, Z Ma, D Liu, W Li, S Di, Y Lai, L Ho, GR Crabtree, CR Clapier, J Iwasa, BR Cairns, CL Peterson, R Yang, N Liu, L Chen, JR Misra, KD Irvine, CG Hansen, YL Ng, WL Lam, SW Plouffe, KL Guan, PC Hsu, DM Jablons, CT Yang, L You, D Jin, J Guo, J Du, S Magesh, D Cai, K Yu, Z Qian, Y Miao, S Qiu, J Cui, D Glick, S Barth, KF Macleod, F Kuang, DJ Klionsky, E Park, SW Chung, B Zhou, JD Mancias, SP Gygi, JW Harper, AC Kimmelman, S Zhu, Q Wen, D Nandi, P Tahiliani, A Kumar, D Chandu, J Park, J Cho, EJ Song, Y Meng, H Sun, S Zhao, J Su, F Zeng, Q Yang, J Chen, L Yao, Z Tang, W Jiang, M Mao, J Zhao, N Cheng, C Meng, J Zhan, G Shao, D Huang, Q Li, Y Tang, Y Qu, M Esteller, Y He, X Jiang, L Duan, Q Xiong, Y Yuan, G Bi, J Liang, M Zhao, X Jin, T Lu, A Malhotra, PTB Ho, IM Clark, LTT Le, MA Iqbal, S Arora, G Prakasam, GA Calin, MA Syed, Z Song, G Jia, P Ma, S Cang, X Lu, N Kang, X Ling, M Pan, W Du, S Gao, D Wei, YQ Ke, P Duan, L Zhou, CY Wang, P Cao, Q Chen, Q Pan, H Gao, X Zhong, LS Kristensen, TB Hansen, MT VenĂž, J Kjems, G Shan, MS Andersen, LVW Stagsted, KK Ebbesen, FA Karreth, PP Pandolfi, Y Luo, Q Zhang, B Lv, Y Shang, O Li, J Kang, JJ Zhang, LW Hu, L Li, W Shanshan, M Hongying, F Jingjing, Y Yiming, R Yu, Y Rui, C Pan, K Wei, J Huang, Z Guo, Y Niu, X Xu, WX Peng, P Koirala, YY Mo, H Lu, S Wu, P Kim, X Zhou, J Yao, R Li, S Su, D Ye, W Lu, X Li, X Sui, N Hu, P Wang, G Xiu, M Wang, L Ouyang, W Lai, C Gai, M Yu, J Zheng, N Zhang, M Xu, T Chen, D Priem, G van Loo, MJM Bertrand, C Gao, F Xiao, Z Aburjania, S Jang, J Whitt, R Jaskula-Stzul, H Chen, JB Rose, J Xiao, M Liu, B Lian, N Vu, M Kim, D Stephenson, H MacKnight, C Chalfant, X Zeng, D Lu, M Yin, M Shan, Y Gao, S Liu, S Yan, J Zhu, R Lu, C Kang, K Tang, B Xu, Q Han, Y Xia, C Gong, AA Abdelgalil, HM Alkahtani, FI Al-Jenoobi, G Blumenschein, E Lachaier, C Louandre, C Godin, Z Saidak, M Baert, M Diouf, L Freire Boullosa, J Van Loenhout, T Flieswasser, J De Waele, C Hermans, H Lambrechts, W Zhou, M Yan, S Lian, K Sun, W Wu, Z Geng, H Bai, T Liu, B Zhang, H Yu, Z Han, Z Xu, C An, L Xu, H Xin, J Kryczka, KH Czarnecka-Chrebelska, E BrzeziaƄska-Lasota, L Galluzzi, L Senovilla, I Vitale, J Michels, I Martins, O Kepp, Z Liang, W Zhao, L Meng, Z Cui, C Abdel Shaheed, GE Ferreira, A Dmitritchenko, AJ McLachlan, RO Day, B Saragiotto, D Ding, J Laengle, J Kabiljo, L Hunter, J Homola, S Prodinger, G Egger, T Zhang, B Sun, C Zhong, K Xu, P Hofman, H Yan, H Liu, C Wu, LF Ye, KR Chaudhary, AD Harken, CJ Kinslow, PS Upadhyayula, CH Hsieh, HC Hsieh, FS Shih, PW Wang, LX Yang, DB Shieh, G Zhu, H Chi, Y Yin, H Diao, Z Liu, C Ge, S Zhang, H Mu, S Zheng, Z Tan, X Huang, US Neill, T Efferth, G Chen, F Benthani, D Liang, Z Bian, X Dai, W Chen, S Mo, H Yi, H Yao, L Lu, G He, M Wu, B Yuan, F Liao, Y Ren, X Deng, T Yang, N Han, X Peng, Q Ma, OA Ahmed Hamdi, SN Syed Abdul Rahman, K Awang, N Abdul Wahab, CY Looi, NF Thomas, R Zhang, T Pan, Y Xiang, M Zhang, H Xie, SW Ng, Y Chan, DK Chellappan, T Madheswaran, F Zeeshan, YL Chan, Y Fan, B Han, F Chen, S Alakurtti, T MĂ€kelĂ€, S Koskimies, J Yli-Kauhaluoma, WY Yan, J Cai, JN Wang, YS Gong, XB Ding, KS Prabhu, AA Bhat, KS Siveen, S Kuttikrishnan, SS Raza, T Raheed, R Xu, J Tian, W Teng, D Boulghobra, PE Grillet, M Laguerre, M Tenon, J Fauconnier, P Fança-Berthon, M Shao, Q Jiang, C Shen, L Qiu, L Zhu, Y Lu, Z Sun, J Han, YY Zeng, YB Luo, XD Ju, YJ Cui, YB Pan, W Koch, W Kukula-Koch, Z Marzec, E Kasperek, L Wyszogrodzka-Koma, W Szwerc, Y Tsai, JC Merritt, SD Richbart, EG Moles, AJ Cox, KC Brown, SL Miles, K Srinivasan, XY Liu, DG Wei, RS Li, Q Wu, J Feng, L Yan, HQ Zhang, XF Xie, GM Li, JR Chen, MT Li, SL Morris-Natschke, KH Lee, CY Wu, YH Yang, YS Lin, GH Chang, MS Tsai, CM Hsu, S Chen, Y Guo, R Zhao, M Jiang, H Fu, UM Nazim, JK Jeong, SY Park, Q Gao, L Gu, A Gepdiremen, V Mshvildadze, H SĂŒleyman, R Elias, D Wang, Y Lou, P Huang, M Jin, M Adnan, A Rasul, G Hussain, MA Shah, MK Zahoor, H Anwar, JS Lou, LP Zhao, ZH Huang, XY Chen, JT Xu, WC Tai, P Waiwut, A Inujima, H Inoue, I Saiki, H Sakurai, B Jiang, M Wan, A Vanduchova, P Anzenbacher, E Anzenbacherova, M Russo, C Spagnuolo, GL Russo, K Skalicka-WoĆșniak, M Daglia, E Sobarzo-SĂĄnchez, Y Iida, M Okamoto-Katsuyama, S Maruoka, K Mizumura, T Shimizu, S Shikano, SM Lee, BS Bae, HW Park, NG Ahn, BG Cho, YL Cho, FG Zhai, QC Liang, YY Wu, JQ Liu, JW Liu, F Huang, J Pang, W Niu, YY Zhao, YQ Yang, HH Sheng, Q Tang, L Han, SM Wang, L Zeng, L Lignitto, SE LeBoeuf, H Homer, S Jiang, M Askenazi, TR Karakousi, M Yamamoto, TW Kensler, H Motohashi, W Cheng, M Guo, M Shen, D Kong, J Shao, C Liang, L Mahoney-SĂĄnchez, H Bouchaoui, S Ayton, D Devos, JA Duce, JC Devedjian Show less
Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, Show more
Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, and radiotherapy. However, due to the strong metastatic characteristics of lung cancer and the emergence of related drug resistance and radiation resistance, the overall survival rate of lung cancer patients is not ideal. There is an urgent need to develop new treatment strategies or new effective drugs to treat lung cancer. Ferroptosis, a novel type of programmed cell death, is different from the traditional cell death pathways such as apoptosis, necrosis, pyroptosis and so on. It is caused by the increase of iron-dependent reactive oxygen species due to intracellular iron overload, which leads to the accumulation of lipid peroxides, thus inducing cell membrane oxidative damage, affecting the normal life process of cells, and finally promoting the process of ferroptosis. The regulation of ferroptosis is closely related to the normal physiological process of cells, and it involves iron metabolism, lipid metabolism, and the balance between oxygen-free radical reaction and lipid peroxidation. A large number of studies have confirmed that ferroptosis is a result of the combined action of the cellular oxidation/antioxidant system and cell membrane damage/repair, which has great potential application in tumor therapy. Therefore, this review aims to explore potential therapeutic targets for ferroptosis in lung cancer by clarifying the regulatory pathway of ferroptosis. Based on the study of ferroptosis, the regulation mechanism of ferroptosis in lung cancer was understood and the existing chemical drugs and natural compounds targeting ferroptosis in lung cancer were summarized, with the aim of providing new ideas for the treatment of lung cancer. In addition, it also provides the basis for the discovery and clinical application of chemical drugs and natural compounds targeting ferroptosis to effectively treat lung cancer. Show less
📄 PDF DOI: 10.1038/s41420-023-01407-z
Fe ROS review
TA Kalyanaraman, N Daver, M Mahendra +242 more · 2023 · Expert opinion on therapeutic targets · Taylor & Francis · added 2026-04-20
TA Kalyanaraman, N Daver, M Mahendra, X Zhang, CV Dang, TM Ashton, WG McKenna, LA Kunz-Schughart, Y Xu, D Xue, A Bankhead, M Huang, CR Myers, Y Wang, B Kalyanaraman, SK Biswas, RAJ Smith, CM Porteous, AM Gane, MP Murphy, RC Hartley, E Fokas, M Benej, X Hong, S Vibhute, M Nishida, N Yamashita, T Ogawa, K Chandran, D Aggarwal, RQ Migrino, D Graham, NN Huynh, CA Hamilton, T Capeloa, J Krzystyniak, D d’Hose, JA Van de Velde, AC Rodriguez, NG Yoon, H Lee, SY Kim, S Yoshida, S Tsutsumi, G Muhlebach, A Rasola, L Neckers, D Picard, G Cheng, H Karoui, M Hardy, F Weinberg, R Hamanaka, WW Wheaton, B Fink, L Coppey, E Davidson, EM Gottwald, M Duss, M Bugarski, J Pan, Y Lee, JR Molina, Y Sun, M Protopopova, J Zielonka, M AbuEid, DM McAllister, L McOlash, IK Srivastava, H Rottenberg, AB Vaidya, PD Radloff, J Philipps, M Nkeyi, W Hughes, G Leoung, F Kramer, CD Freeman, NE Klutman, KC Lamp, A Darade, S Pathak, S Sharma, R Dixon, AL Pozniak, HM Watt, GL Nixon, DM Moss, AE Shone, M Fry, M Pudney, MW Mather, E Darrouzet, M Valkova-Valchanova, M Fiorillo, R Lamb, HB Tanowitz, M Xiang, H Kim, VT Ho, N Gupta, SK Srivastava, S Tian, H Chen, W Tan, D Xiong, P Topchyan, RM Loftus, DK Finlay, G Andrejeva, JC Rathmell, X Li, M Wenes, P Romero, T Gaber, C Strehl, F Buttgereit, A Tasdogan, JM Ubellacker, SJ Morrison, B Faubert, V Ramesh, Q Zhang, LP Burton, G Deng, CD Yanes, SR Lord, AL Harris, ME McGuinness, RL Talbert, H Zhao, KD Swanson, B Zheng, L Di Magno, S Manni, F Di Pastena, SR Veiga, X Ge, CA Mercer, R Masoud, G Reyes-Castellanos, S Lac, F Janku, SH Beom, YW Moon, O Ouari, KA Boyle, J Van Wickle, RB Hill, RF Keyes, D McAllister, Z Bielcikova, J Stursa, L Krizova, K Rohlenova, K Sachaphibulkij, KER Hollinshead, SJ Parker, VV Eapen, S Stemberkova-Hubackova, R Zobalova, M Dubisova, CA Reddy, V Somepalli, T Golakoti, S Jayakumar, RS Patwardhan, D Pal, A Mattarei, M Romio, A ManagĂČ, RK Pathak, S Marrache, DA Harn, DR Boulware, MF Pullen, AS Bangdiwala, S Crunkhorn, LD Zorova, VA Popkov, EY Plotnikov, J Joseph, A Sikora, L Dong, J Neuzil, A Solmonson, RJ DeBerardinis, V Gouirand, F Guillaumond, S Vasseur, GM Fischer, A Jalali, DA Kircher, VS LeBleu, JT O’Connell, KN Gonzalez Herrera, JH Park, S Vithayathil, S Kumar, F Sotgia, D Whitaker-Menezes, UE Martinez-Outschoorn, CR Bartman, DR Weilandt, Y Shen, YG Najjar, AV Menk, C Sander, AR Jaiswal, AJ Liu, S Pudakalakatti, MJ McManus, JL Franklin, RA Smith, B Mathieu, L Mignion, M Skwarski, DR McGowan, E Belcher, M Zielonka, B Dranka, HR Bridges, JG Fedor, JN Blaza, A Naguib, G Mathew, CR Reczek, SE Weinberg, BD Singer, EM Steinert, Z Zhao, Y Mei, Z Wang, K Vasan, M Werner, NS Chandel, EM De Francesco, B ÓzsvĂĄri, S Izreig, A Gariepy, I Kaymak, D Kolb, N Kolishetti, B Surnar Show less
Introduction: Drugs targeting mitochondria are emerging as promising antitumor therapeutics in preclinical models. However, a few of these drugs have shown clinical toxicity. Developing mitochondria- Show more
Introduction: Drugs targeting mitochondria are emerging as promising antitumor therapeutics in preclinical models. However, a few of these drugs have shown clinical toxicity. Developing mitochondria-targeted modified natural compounds and US FDA-approved drugs with increased therapeutic index in cancer is discussed as an alternative strategy. Areas Covered: Triphenylphosphonium cation (TPP + )-based drugs selectively accumulate in the mitochondria of cancer cells due to their increased negative membrane potential, target the oxidative phosphorylation proteins, inhibit mitochondrial respiration, and inhibit tumor proliferation. TPP + -based drugs exert minimal toxic side effects in rodents and humans. These drugs can sensitize radiation and immunotherapies. Expert Opinion: TPP + -based drugs targeting the tumor mitochondrial electron transport chain are a new class of oxidative phosphorylation inhibitors with varying antiproliferative and antimetastatic potencies. Some of these TPP + -based agents, which are synthesized from naturally occurring molecules and FDA-approved drugs, have been tested in mice and did not show notable toxicity, including neurotoxicity, when used at doses under the maximally tolerated dose. Thus, more effort should be directed toward the clinical translation of TPP + -based OXPHOS-inhibiting drugs in cancer prevention and treatment. Show less
no PDF DOI: 10.1080/14728222.2023.2261631
anticancer mitochondria synthesis
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. MartĂ­nez–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. 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S. Haque, M. Kibble, N. Saarinen, F. Iorio, S. MĂ€kelĂ€, 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