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Hypoxia studies in non‑small cell lung cancer: Pathogenesis and clinical implications (Review)

H Zhou, J Ferlay, RL Siegel +660 more · 2025 · Oncology Reports · added 2026-04-20

H Zhou, J Ferlay, RL Siegel, M Laversanne, I Soerjomataram, A Jemal, F Bray, PS Steeg, KD Miller, HE Fuchs, FX Xu, YL Zhang, JJ Liu, DD Zhang, HB Chen, K Saxena, MK Jolly, JA Bertout, SA Patel, MC Simon, X Meng, FM Kong, J Yu, A Challapalli, L Carroll, EO Aboagye, DC Hinshaw, LA Shevde, P Desai, N Takahashi, R Kumar, S Nichols, J Malin, A Hunt, C Schultz, Y Cao, D Tillo, D Nousome, FF Tam, KL Ning, M Lee, JM Dumlao, JC Choy, AA Tirpe, D Gulei, SM Ciortea, C Crivii, I Berindan-Neagoe, EB Rankin, AJ Giaccia, GN Masoud, W Li, Y Della Rocca, L Fonticoli, TS Rajan, O Trubiani, S Caputi, F Diomede, J Pizzicannella, GD Marconi, SG Zeng, X Lin, JC Liu, J Zhou, RY Hapke, SM Haake, S Musleh Ud Din, SG Streit, BT Huynh, C Hana, AN Abraham, A Hussein, S Liu, Y Zhan, J Luo, J Feng, J Lu, H Zheng, Q Wen, S Fan, C Wang, S Xu, X Yang, W Luo, H Hu, R Chang, J Zhong, M Knabel, R O'Meally, RN Cole, A Pandey, GL Semenza, Y Wei, D Wang, F Jin, Z Bian, L Li, H Liang, M Li, L Shi, C Pan, D Zhu, X Ji, R Zhu, C Gao, H Xie, X Gong, H Jiang, H Zhao, M Zhang, Y He, X Li, Y Xu, X Liu, S Jiang, R Wang, H Yan, L Jin, X Dou, D Chen, V Becker, X Yuan, AS Boewe, E Ampofo, E Ebert, J Hohneck, RM Bohle, E Meese, Y Zhao, MD Menger, J Zhao, CR Qiao, Z Ding, YL Sheng, XN Li, Y Yang, DY Zhu, CY Zhang, DL Liu, K Wu, S Zhao, C Han, Y Zhang, F Liu, J Ren, HL Yin, HW Xu, QY Lin, RD Leone, JD Powell, Z Yu, J Zou, F Xu, J Jin, G Yu, J Gu, S Yang, X Wang, Y Wu, J Wei, J Xu, AL Jackson, B Zhou, WY Kim, KL Eales, KER Hollinshead, DA Tennant, E Dai, W Wang, Y Li, D Ye, R Courtnay, DC Ngo, N Malik, K Ververis, SM Tortorella, TC Karagiannis, F Luo, N Yan, S Li, G Cao, Q Cheng, Q Xia, H Wang, S Shang, MZ Wang, Z Xing, N He, H Nisar, PM Sanchidrián González, M Brauny, FM Labonté, C Schmitz, MD Roggan, B Konda, CE Hellweg, Z Guo, L Hu, Q Wang, Y Wang, XP Liu, C Chen, W Hu, X Zhang, C Liang, C Wu, S Wan, L Xu, S Wang, J Wang, X Huang, C Zhang, L Zhou, Y Du, C Li, H Ren, L Zheng, PE Porporato, N Filigheddu, JMB Pedro, G Kroemer, L Galluzzi, OT Brustugun, RX Huang, PK Zhou, H Chen, Z Han, Q Luo, Q Li, H Zuo, L Gong, C Liu, S Han, T Zhou, LY Zhang, JZ He, ZM Miao, YY Li, YM Zhang, ZW Liu, SZ Zhang, Y Chen, GC Zhou, YQ Liu, LH Gray, AD Conger, M Ebert, S Hornsey, OC Scott, AB Herrera-Campos, E Zamudio-Martinez, D Delgado-Bellido, M Fernández-Cortés, LM Montuenga, FJ Oliver, A Garcia-Diaz, Q Guo, F Lan, X Yan, Z Xiao, Q Zhang, S Roy, S Kumaravel, A Sharma, CL Duran, KJ Bayless, S Chakraborty, CY Hu, CF Hung, PC Chen, JY Hsu, CT Wang, MD Lai, YS Tsai, AL Shiau, GS Shieh, CL Wu, A Mancino, T Schioppa, P Larghi, F Pasqualini, M Nebuloni, IH Chen, S Sozzani, JM Austyn, A Mantovani, A Sica, X Peng, J Huang, Y Tao, HK Eltzschig, LF Thompson, J Karhausen, RJ Cotta, JC Ibla, SC Robson, SP Colgan, J Li, L Wang, X Chen, Y Ping, L Huang, D Yue, Z Zhang, F Wang, SM An, HM Lei, XP Ding, F Sun, YB Tang, HZ Chen, Y Shen, L Zhu, A Kogita, Y Togashi, H Hayashi, S Sogabe, M Terashima, MA De Velasco, K Sakai, Y Fujita, S Tomida, Y Takeyama, S Karan, MY Cho, H Lee, HS Park, M Sundararajan, JL Sessler, KS Hong, MHY Cheng, Y Mo, G Zheng, LC Clark, R Wolf, D Granger, Z Taylor, X Sun, G Niu, N Chan, B Shen, MV Shirmanova, MM Lukina, MA Sirotkina, LE Shimolina, VV Dudenkova, NI Ignatova, S Tobita, VI Shcheslavskiy, EV Zagaynova, JM Vanderkooi, G Maniara, TJ Green, DF Wilson, CJ Koch, SM Evans, MR Horsman, BS Sørensen, M Busk, DW Siemann, C Huang, J Liang, X Lei, X Xu, L Luo, X Hu, J Gou, W Lin, F Yang, C Liao, D Nasri, R Manwar, A Kaushik, EE Er, K Avanaki, KA Krohn, JM Link, RP Mason, JR Brender, Y Saida, N Devasahayam, MC Krishna, S Kishimoto, I Godet, S Doctorman, F Wu, DM Gilkes, K Matsumoto, JB Mitchell, W Qin, C Xu, C Yu, S Shen, W Huang, DS Vikram, JL Zweier, P Kuppusamy, B Epel, MK Bowman, C Mailer, HJ Halpern, B Hao, H Dong, R Xiong, C Song, N Li, Q Geng, R Zhang, L Lai, J He, D You, W Duan, X Dong, Y Zhu, L Lin, C Ostheimer, M Bache, A Güttler, M Kotzsch, D Vordermark, A Giatromanolaki, AL Harris, AH Banham, CA Contrafouris, MI Koukourakis, H Geng, L Chen, S Lv, SJ Kim, ZN Rabbani, RT Vollmer, EG Schreiber, E Oosterwijk, MW Dewhirst, Z Vujaskovic, MJ Kelley, D Coppola, M Szabo, D Boulware, P Muraca, M Alsarraj, AF Chambers, TJ Yeatman, T Reese, K Stępień, RP Ostrowski, E Matyja, SW Kim, IK Kim, JH Ha, CD Yeo, HH Kang, JW Kim, SH Lee, O Thews, P Vaupel, M Heyboer, D Sharma, W Santiago, N McCulloch, LW Jones, BL Viglianti, JA Tashjian, SM Kothadia, ST Keir, SJ Freedland, MQ Potter, EJ Moon, T Schroeder, JE Herndon, S Jo, J Jeon, G Park, HK Do, J Kang, KJ Ahn, SY Ma, YM Choi, D Kim, B Youn, Y Ki, P Ghosh, C Vidal, S Dey, L Zhang, TM Ashton, WG McKenna, LA Kunz-Schughart, GS Higgins, B Kalyanaraman, G Cheng, M Hardy, M You, M Shameem, AJ Bagherpoor, A Nakhi, P Dosa, G Georg, F Kassie, M Skwarski, DR McGowan, E Belcher, F Di Chiara, D Stavroulias, M McCole, JL Derham, KY Chu, E Teoh, J Chauhan, M Benej, X Hong, S Vibhute, S Scott, J Wu, E Graves, QT Le, AC Koong, B Yu, S Sohoni, T Wang, SP Kalainayakan, PC Konduri, A Ashrafi, P Modareszadeh, N Salamat, PS Alemi, E Berisha, TW Secomb, V Sukhatme, G Bouche, L Meheus, VP Sukhatme, P Pantziarka, BJT Reymen, MW van Gisbergen, AJG Even, CML Zegers, M Das, E Vegt, JE Wildberger, FM Mottaghy, A Yaromina, LJ Dubois, PP Wong, N Bodrug, KM Hodivala-Dilke, S Guelfi, K Hodivala-Dilke, G Bergers, C Wigerup, S Påhlman, D Bexell, Y Xia, HK Choi, K Lee, L Iommarini, AM Porcelli, G Gasparre, I Kurelac, N Albadari, S Deng, J Ma, K Cao, X Ling, P Zhang, J Zhu, H Deng, P Li, Q Hang, Y Jin, M Chen, MS Lara, CM Blakely, JW Riess, H Zhu, S Zhang, W Tian, C Cao, L Shu, A Mahdi, B Darvishi, K Majidzadeh-A, M Salehi, L Farahmand, Z Xie, T Zou, JL Bryant, SL Meredith, KJ Williams, A White, WR Wilson, MP Hay, SX Chen, J Zhang, F Xue, W Liu, Y Kuang, B Gu, S Song, F Shepherd, G Koschel, J Von Pawel, U Gatzmeier, N Van Zandwiyk, P Woll, R Van Klavren, P Krasko, P Desimone, M Nicolson, L Marcu, I Olver, K Graham, E Unger, D Lindsay, CM Garvey, SM Mumenthaler, J Foo, C Meaney, GG Powathil, P Lambin, M Kohandel, BT Oronsky, SJ Knox, JJ Scicinski, B Oronsky, J Scicinski, S Ning, D Peehl, A Oronsky, P Cabrales, M Bednarski, S Knox, L Zhao, C Shen, Y Luo, X Hou, Y Qi, Z Huang, L Gao, M Wu, Y Zhou, X Feng, Z Wu, X Rao, R Zhou, R Meng, P Dey, R Das, S Chatterjee, R Paul, U Ghosh, Y Demizu, O Fujii, H Iwata, N Fuwa, SM Bentzen, V Gregoire, G Meijer, J Steenhuijsen, M Bal, K De Jaeger, D Schuring, J Theuws Show less

Non-small cell lung cancer (NSCLC) is one of the most prevalent and lethal types of cancers worldwide and its high incidence and mortality rates pose a significant public health challenge. Despite significant advances in targeted therapy and immunotherapy, the overall prognosis of patients with NSCLC remains poor. Hypoxia is a critical driving factor in tumor progression, influencing the biological behavior of tumor cells through complex molecular mechanisms. The present review systematically examined the role of the hypoxic microenvironment in NSCLC, demonstrating its crucial role in promoting tumor cell growth, invasion and metastasis. Additionally, it has been previously reported that the hypoxic microenvironment enhances tumor cell resistance by activating hypoxia-inducible factor and regulating exosome secretion. The hypoxic microenvironment also enables tumor cells to adapt to low oxygen and nutrient-deficient conditions by enhancing metabolic reprogramming, such as through upregulating glycolysis. Further studies have shown that the hypoxic microenvironment facilitates immune escape by modulating tumor-associated immune cells and suppressing the antitumor response of the immune system. Moreover, the hypoxic microenvironment increases tumor resistance to radiotherapy, chemotherapy and other types of targeted therapy through various pathways, significantly reducing the therapeutic efficacy of these treatments. Therefore, it could be suggested that early detection of cellular hypoxia and targeted therapy based on hypoxia may offer new therapeutic approaches for patients with NSCLC. The present review not only deepened the current understanding of the mechanisms of action and role of the hypoxic microenvironment in NSCLC but also provided a solid theoretical basis for the future development of precision treatments for patients with NSCLC. Show less

📄 PDF DOI: 10.3892/or.2024.8862

anticancer review

Summary The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but these tumors quickly develop resistance to this treatment. We have observed increased phosphorylation of AKT1/mTOR/4EBP1 and levels of p21 in FOLFOX-resistant CRC cells. We have identified a small molecule, NSC49L, that stimulates protein phosphatase 2A (PP2A) activity, downregulates the AKT1/mTOR/4EBP1-axis, and inhibits p21 translation. We have provided evidence that NSC49L- and TRAIL-mediated sensitization is synergistically induced in p21-knockdown CRC cells, which is reversed in p21-overexpressing cells. p21 binds with procaspase 3 and prevents the activation of caspase 3. We have shown that TRAIL induces apoptosis through the activation of caspase 3 by NSC49L-mediated downregulation of p21 translation, and thereby cleavage of procaspase 3 into caspase 3. NSC49L does not affect global protein synthesis. These studies provide a mechanistic understanding of NSC49L as a PP2A agonist, and how its combination with TRAIL sensitizes FOLFOX-resistant CRC cells. Show less

👤 MJ Kelley

Hypoxia studies in non‑small cell lung cancer: Pathogenesis and clinical implications (Review)

Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A