2,336
Views
6
CrossRef citations to date
0
Altmetric
Review

Harnessing the vulnerabilities of p53 mutants in lung cancer – Focusing on the proteasome: a new trick for an old foe?

&
Pages 293-302 | Received 14 Jul 2019, Accepted 01 Dec 2019, Published online: 10 Feb 2020

References

  • World Health Organization. Cancer. [accessed 2019 July 13]. https://www.who.int/news-room/fact-sheets/detail/cancer.
  • Siegel RL, Miller KD, Jemal A. 2019. Cancer statistics, 2019. CA Cancer J Clin. 69:7–34. doi:10.3322/caac.21551.
  • Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, RA O, BW B, Harris PL, Haserlat SM, Supko JG, Haluska FG, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–2139. doi:10.1056/NEJMoa040938.
  • Nasim F, BF S, GA E. 2019. Lung cancer. Med Clin North Am. 103:463–473. doi:10.1016/j.mcna.2018.12.006.
  • Anagnostou VK, Brahmer JR. 2015. Cancer immunotherapy: A future paradigm shift in the treatment of non-small cell lung cancer. Clin Cancer Res. 21:976–984. doi:10.1158/1078-0432.CCR-14-1187.
  • Peifer M, Fernández-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, Plenker D, Leenders F, Sun R, Zander T, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet. 2012;44:1104–1110. doi:10.1038/ng.2396.
  • Shetzer Y, Molchadsky A, Rotter V. Oncogenic mutant p53 gain of function nourishes the vicious cycle of tumor development and cancer stem-cell formation. Cold Spring Harb Perspect Med. 2016;6;a026203. doi:10.1101/cshperspect.a026203.
  • Oren M, Rotter V. 2010. Mutant p53 gain-of-function in cancer. Cold Spring Harb Perspect Biol. 2:a001107. doi:10.1101/cshperspect.a001107.
  • Olive KP, Tuveson DA, Ruhe ZC, Yin B, Willis NA, Bronson RT, Crowley D, Jacks T. 2004. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell. 2004:847–860. doi:10.1016/j.cell.2004.11.004.
  • Alexandrova EM, Yallowitz AR, Li D, Xu S, Schulz R, Proia DA, Lozano G, Dobbelstein M, Moll UM. 2015. Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment. Nature. 523:352–356. doi:10.1038/nature14430.
  • Alexandrova EM, Mirza SA, Xu S, Schulz-Heddergott R, Marchenko ND, Moll UM. P53 loss-of-heterozygosity is a necessary prerequisite for mutant p53 stabilization and gain-of-function in vivo. Cell Death Dis. 2017;8. doi:10.1038/cddis.2017.80.
  • National Institutes of Health. ClinicalTrials.gov. [accessed 2019 Oct 28]. https://clinicaltrials.gov/ct2/results?cond=apr+246&term=&cntry=&state=&city=&dist=&Search=Search.
  • National Institutes of Health. ClinicalTrials.gov. [accessed 2019 Oct 28]. https://clinicaltrials.gov/ct2/results?cond=&term=hsp90+inhibitor&cntry=&state=&city=&dist=.
  • Halasi M, Pandit B, Gartel AL. 2014. Proteasome inhibitors suppress the protein expression of mutant p53. Cell Cycle. 13:3202–3206. doi:10.4161/15384101.2014.950132.
  • An WG, Chuman Y, Fojo T, Blagosklonny MV. 1998. Inhibitors of transcription, proteasome inhibitors, and DNA-damaging drugs differentially affect feedback of p53 degradation. Exp Cell Res. 244:54–60. doi:10.1006/excr.1998.4193.
  • Choudhury S, Kolukula VK, Preet A, Albanese C, Avantaggiati ML. 2013. Dissecting the pathways that destabilize mutant p53: the proteasome or autophagy? Cell Cycle. 12:1022–1029. doi:10.4161/cc.24128.
  • Walerych D, Lisek K, Sommaggio R, Piazza S, Ciani Y, Dalla E, Rajkowska K, Gaweda-Walerych K, Ingallina E, Tonelli C, et al. Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer. Nat Cell Biol. 2016;18:897–909. doi:10.1038/ncb3380.
  • Ali A, Wang Z, Fu J, Ji L, Liu J, Li L, Wang H, Chen J, Caulin C, Myers JN, et al. Differential regulation of the REGγ-proteasome pathway by p53/TGF-β signalling and mutant p53 in cancer cells. Nat Commun. 2013;4:2667. doi:10.1038/ncomms3667.
  • Vousden KH, Lu X. 2002. Live or let die: the cell’s response to p53. Nat Rev Cancer. 2:594–604. doi:10.1038/nrc864.
  • Vogelstein B, Lane D, Levine AJ. 2000. Surfing the p53 network. Nature. 408:307–310. doi:10.1038/35042675.
  • Lu H, Levine AJ. 1995. Human TAFII31 protein is a transcriptional coactivator of the p53 protein. Proc Natl Acad Sci U S A. 92:5154–5158. doi:10.1073/pnas.92.11.5154.
  • Walker KK, Levine AJ. 2002. Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc Natl Acad Sci. 93:15335–15340. doi:10.1073/pnas.93.26.15335.
  • Joerger AC, Fersht AR. The tumor suppressor p53: from structures to drug discovery. Cold Spring Harb Perspect Biol. 2010;2. doi:10.1101/cshperspect.a000919.
  • Chène P. 2001. The role of tetramerization in p53 function. Oncogene. 20:2611–2617. doi:10.1038/sj.onc.1204373.
  • Weinberg RL, Freund SMV, Veprintsev DB, Bycroft M, Fersht AR. Regulation of DNA binding of p53 by its C-terminal domain. J Mol Biol. 2004;342:801–811. doi:10.1016/j.jmb.2004.07.042.
  • Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature. 1993;362:857–860. doi:10.1038/362857a0.
  • Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell. 1992. doi:10.1016/0092-8674:90644-R
  • Grossman SR, Deato ME, Brignone C. Polyubiquitination of p53 by a ubiquitin ligase activity of p300. Science. 2003;300:342–344. doi:10.1126/science.1080386.
  • Grossman SR, Perez M, Kung AL, Joseph M, Mansur C, Xiao Z-X, Kumar S, Howley PM, Livingston DM. 1998. p300/MDM2 complexes participate in MDM2-mediated p53 degradation. Mol Cell. 2:405–415. doi:10.1016/S1097-2765(00)80140-9.
  • Craig AL, Burch L, Vojtesek B, Mikutowska J, Thompson A, Hupp TR. 2015. Novel phosphorylation sites of human tumour suppressor protein p53 at Ser 20 and Thr 18 that disrupt the binding of mdm2 (mouse double minute 2) protein are modified in human cancers. Biochem J. 342:133–141. doi:10.1042/bj3420133.
  • Appella E, Anderson CW. 2001. Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem. 268:2764–2772. doi:10.1046/j.1432-1327.2001.0222x.
  • Ou YH, Chung PH, Sun TP, SS Y. 2005. p53 C-terminal phosphorylation by CHK1 and CHK2 participates in the regulation of DNA-damage-induced C-Terminal acetylation. Mol Biol Cell. 16:1684–1695. doi:10.1091/mbc.e04-08-0689.
  • Yogosawa S, Yoshida K. 2018. Tumor suppressive role for kinases phosphorylating p53 in DNA damage-induced apoptosis. Cancer Sci. 109:3376–3382. doi:10.1111/cas.13792.
  • Chehab NH, Malikzay A, Stavridi ES, Halazonetis TD. 1999. Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc Natl Acad Sci U S A. 96:13777–13782. doi:10.1073/pnas.96.24.13777.
  • Shieh SY, Ikeda M, Taya Y, Prives C. 1997. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell. 91:325–334. doi:10.1016/S00928674(00)80416-X.
  • Lambert PF, Kashanchi F, Radonovich MF, Shiekhattar R, Brady JN. 1998. Phosphorylation of p53 serine 15 increases interaction with CBP. J Biol Chem. 273:33048–33053. doi:10.1074/jbc.273.49.33048.
  • Ito A, Lai CH, Zhao X, Saito S, Hamilton MH, Appella E, Yao T-P. 2001. p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. Embo J. 20:1331–1340. doi:10.1093/emboj/20.6.1331.
  • Laptenko O, Prives C. 2006. Transcriptional regulation by p53: one protein, many possibilities. Cell Death Differ. 13:951–996. doi:10.1038/sj.cdd.4401916.
  • Harris SL, Levine AJ. 2005. The p53 pathway: positive and negative feedback loops. Oncogene. 23:2899–2908. doi:10.1038/sj.onc.1208615.
  • Wasylishen AR, Lozano G. Attenuating the p53 pathway in human cancers: many means to the same end. Cold Spring Harb Perspect Med. 2016;6. doi:10.1101/cshperspect.a026211.
  • Lukashchuk N, Vousden KH. 2007. Ubiquitination and degradation of Mutant p53. Mol Cell Biol. 27:8284–8295. doi:10.1128/mcb.00050-07.
  • Li D, Marchenko ND, Schulz R, Fischer V, Velasco-Hernandez T, Talos F, Moll UM. 2011. Functional inactivation of endogenous MDM2 and CHIP by HSP90 causes aberrant stabilization of mutant p53 in human cancer cells. Mol Cancer Res. 9:577–588. doi:10.1158/1541-7786.mcr-10-0534.
  • Hu B, Gilkes DM, Farooqi B, Sebti SM, Chen J. 2006. MDMX overexpression prevents p53 activation by the MDM2 inhibitor nutlin. J Biol Chem. 281:33030–33035. doi:10.1074/jbc.C600147200.
  • Shvarts A, Bazuine M, Dekker P, Ramos YFM, Steegenga WT, Merckx G, RCA VH, van der Houven van Oordt W, van der Eb AJ, AG J, et al. Isolation and identification of the human homolog of a new p53-binding protein, Mdmx. Genomics. 1997;43:34–42. doi:10.1006/geno.1997.4775.
  • Hoffman Y, Pilpel Y, MicroRNAs OM. 2014. Alu elements in the p53-Mdm2-Mdm4 regulatory network. J Mol Cell Biol. 6:192–197. doi:10.1093/jmcb/mju020.
  • Park SY, Lee JH, Ha M, Nam JW, Kim VN. 2009. miR-29 miRNAs activate p53 by targeting p85α and CDC42. Nat Struct Mol Biol. 16:23–29. doi:10.1038/nsmb.1533.
  • Bou Kheir T, Futoma-Kazmierczak E, Jacobsen A. miR-449 inhibits cell proliferation and is down-regulated in gastric cancer. Mol Cancer. 2011;10. doi:10.1186/1476-4598-10-29.
  • Suh -S-S, Yoo JY, Nuovo GJ, Jeon Y-J, Kim S, Lee TJ, Kim T, Bakacs A, RH A, Kaur B, et al. MicroRNAs/TP53 feedback circuitry in glioblastoma multiforme. Proc Natl Acad Sci. 2012;109:5316–5321. doi:10.1073/pnas.1202465109.
  • Olivier M, Goldgar DE, Sodha N, Ohgaki H, Kleihues P, Hainaut P, Eeles RA. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res. 2003;63:6643–6650.
  • Li FP, Fraumeni JF, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, Miller RW. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988;48:5358–5362.
  • Hollstein M, Sidransky D, Vogelstein B, Curtis C. Human Cancers. Science. 1991;253:49–53. doi:10.1126/science.1905840.
  • Olivier M, Hollstein M, Hainaut P. 2010. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 1:a001008. doi:10.1101/cshperspect.a001008.
  • Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, Hainaut P. 2002. The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat. 19:607–614. doi:10.1002/humu.10081.
  • Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, Meert AP, Vallot F, Lafitte JJ, Sculier JP. 2001. Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J. 18:705–719. doi:10.1183/09031936.01.00062201.
  • Mitsudomi T, Hamajima N, Ogawa M, Takahashi T. Prognostic significance of p53 alterations in patients with non-small cell lung cancer: a meta-analysis. Clinical Cancer Res. 2000;6:4055–4063.
  • Gu J, Zhou Y, Huang L, Ou W, Wu J, Li S, Liu B. TP53 mutation is associated with a poor clinical outcome for non-small cell lung cancer: evidence from a meta-analysis. Molecular and Clinical Oncology. 2016;5:705–713. doi:doi.10.3892/mco.2016.1057.
  • Kandioler D, Stamatis G, Eberhardt W, Kappel S, Zöchbauer-Müller S, Kührer I, Mittlböck M, Zwrtek R, Aigner C, Bichler C. 2008. Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer. J Thoracic Cardiovasc Surg. 135:1036–1041. doi:10.1016/j.jtcvs.2007.10.072.
  • Campling BG, El-Deiry WS. 2003. Clinical implication of p53 mutation in lung cancer. Mol Biotechnol. 24:141–156. doi:10.1385/MB:24:2:141.
  • Ciechanover A. 2005. Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol. 6:79–86. doi:10.1038/nrm1552.
  • Recognition FD. 2009. Processing of Ubiquitin-protein conjugates by the proteasome. Annu Rev Biochem. 78:477–513. doi:10.1146/annurev.biochem.78.081507.101607.
  • Pickart CM, Cohen RE. 2004. Proteasomes and their kin: proteases in the machine age. Nat Rev Mol Cell Biol. 5:177–187. doi:10.1038/nrm1336.
  • Vaughan CA, Pearsall I, Singh S, Windle B, Deb SP, Grossman SR, Yeudall WA, Deb S. 2016. Addiction of lung cancer cells to GOF p53 is promoted by up-regulation of epidermal growth factor receptor through multiple contacts with p53 transactivation domain and promoter. Oncotarget. 7:12426–12446. doi:10.18632/oncotarget.6998.
  • Kubbutat MHG, Jones SN, Vousden KH. 1997. Regulation of p53 stability by Mdm2. Nature. 387:299–303. doi:10.1038/387299a0.
  • Kubbutat MHG, Ludwig RL, Ashcroft M, Vousden KH. 2015. Regulation of Mdm2-directed degradation by the C terminus of p53. Mol Cell Biol. 18:5690–5698. doi:10.1128/mcb.18.10.5690.
  • Joerger AC, Fersht AR. 2007. Structure-function-rescue: the diverse nature of common p53 cancer mutants. Oncogene. 26:2226–2242. doi:10.1038/sj.onc.1210291.
  • Midgley CA, Lane DP. 1997. P53 protein stability in tumour cells is not determined by mutation but is dependent on Mdm2 binding. Oncogene. 15:1179–1189. doi:10.1038/sj.onc.1201459.
  • Buschmann T, Minamoto T, Wagle N, Fuchs SY, Adler V, Mai M, Ronai Z. 2000. Analysis of JNK, Mdm2 and p14(ARF) contribution to the regulation of mutant p53 stability. J Mol Biol. 295:1009–1021. doi:10.1006/jmbi.1999.3387.
  • Shimizu H, Saliba D, Wallace M, Finlan L, PRR L-S, Hupp TR. 2006. Destabilizing missense mutations in the tumour suppressor protein p53 enhance its ubiquitination in vitro and in vivo. Biochem J. 397:355–367. doi:10.1042/bj20051521.
  • Prives C, White E. 2008. Does control of mutant p53 by Mdm2 complicate cancer therapy? Genes Dev. 22:1259–1264. doi:10.1101/gad.1680508.
  • Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M, Levine AJ. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol. 1988;8(531–539):PMC363177. doi:10.1128/MCB.8.2.531.
  • Whitesell L, Sutphin PD, Pulcini EJ, Martinez JD, Cook PH. 2015. The physical association of multiple molecular chaperone proteins with mutant p53 is altered by geldanamycin, an hsp90-binding agent. Mol Cell Biol. 18:1517–1524. doi:10.1128/mcb.18.3.1517.
  • Peng Y, Chen L, Li C, Lu W, Chen J. 2001. Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization. J Biol Chem. 276:40583–40590. doi:10.1074/jbc.M102817200.
  • Schulz-Heddergott R, Moll UM. 2018. Gain-of-function (GOF) mutant p53 as actionable therapeutic target. Cancers (Basel). 10:1–16. doi:10.3390/cancers10060188.
  • Muller P, Hrstka R, Coomber D, Lane DP, Vojtesek B. 2008. Chaperone-dependent stabilization and degradation of p53 mutants. Oncogene. 27:3371–3383. doi:10.1038/sj.onc.1211010.
  • Esser C, Scheffner M, Höhfeld J. 2005. The chaperone-associated ubiquitin ligase CHIP is able to target p53 for proteasomal degradation. J Biol Chem. 280:27443–27448. doi:10.1074/jbc.M501574200.
  • Frum RA, Love IM, Damle PK, Mukhopadhyay ND, Palit Deb S, Deb S, Grossman SR. 2016. Constitutive activation of DNA damage checkpoint signaling contributes to mutant p53 accumulation via modulation of p53 ubiquitination. Mol Cancer Res. 14:423–436. doi:10.1158/1541-7786.mcr-15-0363.
  • Lisek K, Walerych D, Del Sal G. 2017. Mutant p53–Nrf2 axis regulates the proteasome machinery in cancer. Mol Cell Oncol. 4:e1217967. doi:10.1080/23723556.2016.1217967.
  • Mortenson MM, Schlieman MG, Virudachalam S, Bold RJ. 2004. Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapy in the A549 non-small-cell lung cancer cell line. Cancer Chemother Pharmacol. 54:343–353. doi:10.1007/s00280-004-0811-4.
  • Yang Y, Ikezoe T, Saito T, Kobayashi M, Koeffler HP, Taguchi H. 2004. Proteasome inhibitor PS-341 induces growth arrest and apoptosis of non-small cell lung cancer cells via the JNK/c-Jun/AP-1 signaling. Cancer Sci. 95:176–180. doi:10.1111/j.1349-7006.2004.tb03200.x.
  • Xue Y, Barker N, Hoon S, He P, Thakur T, Abdeen SR, Maruthappan P, Ghadessy FJ, Lane DP, Stabilizes B. 2019. Activates p53 in proliferative compartments of both normal and tumor tissues in vivo. Cancer Res. 79:3595–3607. doi:10.1158/0008-5472.CAN-18-3744.
  • Hideshima T, Chauhan D, Schlossman R, Richardson P, Anderson KC. 2001. The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene. 20:4519–4527. doi:10.1038/sj.onc.1204623.
  • Chauhan D, Uchiyama H, Akbarali Y, Urashima M, Yamamoto KI, Libermann TA, Anderson KC. Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B. Blood. 1996;87:1104–1112. doi:10.1182/blood.V87.3.1104.bloodjournal8731104.
  • Hideshima T, Chauhan D, Richardson P, Mitsiades C, Mitsiades N, Hayashi T, Munshi N, Dang L, Castro A. 2002. Palombella V NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem. 277:16639–16647. doi:10.1074/jbc.M200360200.
  • Roy P, Sarkar UA, Basak S. 2018. The NF-κB activating pathways in multiple myeloma. Biomedicines. 6:59. doi:10.3390/biomedicines6020059.
  • Demchenko YN, Kuehl WM. A critical role for the NFkB pathway in multiple myeloma. Oncotarget. 2010;1(1):59–68. doi:10.18632/oncotarget.109.
  • Denlinger CE, Rundall BK, Keller MD, Jones DR. Proteasome inhibition sensitizes non-small-cell lung cancer to gemcitabine-induced apoptosis. Ann Thorac Surg. 2004;781207–781214. doi:10.1016/j.athoracsur.2004.04.029.
  • Ling Y, Liebes L. Mechanisms of proteasome inhibitor PS-341-induced G 2 -M-Phase arrest and apoptosis in human non-small cell lung cancer cell lines. Clin Cancer Res. 2003;9:1145–1154.
  • Schenkein DP. Preclinical data with bortezomib in lung cancer. Clin Lung Cancer. 2005;7(Suppl 2):S49–55. doi:10.3816/CLC.2005.s.008.
  • Teicher BA, Ara G, Herbst R, Palombella VJ, Adams J. The proteasome inhibitor PS-341 in cancer theraapy. Clin Cancer Res. 1999;5:2638–2645.
  • Sunwoo JB, Chen Z, Dong G, Yeh N, Crowl Bancroft C, Sausville E, Adams J, Elliott P, Van Waes C. Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor- B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. Clin Cancer Res. 2001;7:1419–1428.
  • Boccadoro M, Morgan G, Cavenagh J. Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int. 2005;5:18. Published 2005 Jun 1. doi:10.1186/1475-2867-5-18.
  • Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S, Elliott PJ, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 1999;59:2615–2622.
  • Frankel A, Man S, Elliott P, Adams J, Kerbel RS. Lack of multicellular drug resistance observed in human ovarian and prostate carcinoma treated with the proteasome inhibitor PS-341. Clin Cancer Res. 2000;6:3719–3728.
  • Mack PC, Davies AM, Lara PN, Gumerlock PH, Gandara DR. Integration of the proteasome inhibitor PS-341(Velcade) into the therapeutic approach to. Lung Cancer. Lung Cancer. 2003;41(suppl1):S89–S9. doi:10.1016/S0169-5002(03)00149-1.
  • Davies AM, Ho C, Metzger AS, Beckett LA, Christensen S, Tanaka M, Lara PN, Lau DH, Gandara DR. 2007. Phase I study of two different schedules of bortezomib and pemetrexed in advanced solid tumors with emphasis on non-small cell lung cancer. J Thorac Oncol. 2:1112–1116. doi:10.1097/JTO.0b013e31815ba7d0.
  • Dudek AZ, Lesniewski-Kmak K, Shehadeh NJ, Pandey ON, Franklin M, Kratzke RA, Greeno EW, Kumar P. 2009. Phase I study of bortezomib and cetuximab in patients with solid tumours expressing epidermal growth factor receptor. Br J Cancer. 100:1379–1384. doi:10.1038/sj.bjc.6605043.
  • Bommakanti SV, Dudek AZ, Khatri A, Kirstein MN, Gada PD. 2011. Phase 1 trial of gemcitabine with bortezomib in elderly patients with advanced solid tumors. Am J Clin Oncol Cancer Clin Trials. 34:597–602. doi:10.1097/COC.0b013e3181f9441f.
  • Voortman J, Smit EF, Honeywell R, Kuenen BC, Peters GJ, van de Velde H, Giaccone G. 2007. A parallel dose-escalation study of weekly and twice-weekly bortezomib in combination with gemcitabine and cisplatin in the first-line treatment of patients with advanced solid tumors. Clin Cancer Res. 13:3642–3651. doi:10.1158/1078-0432.CCR-07-0061.
  • Jones DR, Moskaluk CA, Gillenwater HH, Petroni GR, Burks SG, Philips J, Rehm PK, Olazagasti J, Kozower BD, Bao Y. 2012. Phase I trial of induction histone deacetylase and proteasome inhibition followed by surgery in non-small-cell lung cancer. J Thorac Oncol. 7:1683–1690. doi:10.1097/JTO.0b013e318267928d.
  • Millward M, Price T, Townsend A, Sweeney C, Spenser A, Sukumaran S, Longenecker A, Lee L, Lay A, Sharma G, et al. Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination. Invest New Drugs. 2012;30:2303–2317. doi:10.1007/s10637-011-9766-6.
  • Fanucchi MP, Fossella FV, Belt R, Natale R, Fidias P, Carbone DP, Govindan R, Raez LE, Robert F, Ribiero M. 2006. Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer. J Clin Oncol. 24:5025–5033. doi:10.1200/JCO.2006.06.1853.
  • Lynch TJ, Fenton D, Hirsh V, Bodkin D, Middleman EL, Chiappori A, Halmos B, Favis R, Liu H, WL T, et al. A randomized phase 2 study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer. J Thorac Oncol. 2009;4:1002–1009. doi:10.1097/JTO.0b013e3181aba89f.
  • Lilenbaum R, Wang X, Gu L, Kirshner J, Lerro K, Vokes E. 2009. Randomized phase II trial of docetaxel plus cetuximab or docetaxel plus bortezomib in patients with advanced non-small-cell lung cancer and a performance status of 2: CALGB 30402. J Clin Oncol. 27:4487–4491. doi:10.1200/JCO.2009.22.7066.
  • Scagliotti GV, Germonpré P, Bosquée L, Vansteenkiste J, Gervais R, Planchard D, Reck M, De Marinis F, Lee JS, Park K. 2010. A randomized phase II study of bortezomib and pemetrexed, in combination or alone, in patients with previously treated advanced non-small-cell lung cancer. Lung Cancer. 68:420–426. doi:10.1016/j.lungcan.2009.07.011.
  • Lara PN, Longmate J, Reckamp K, Gitlitz B, Argiris A, Ramalingam S, Belani CP, Mack PC, Lau DHM, Koczywas M, et al. Randomized phase II trial of concurrent versus sequential bortezomib plus docetaxel in advanced non-small-cell lung cancer: A california cancer consortium trial. Clin Lung Cancer. 2011;12:33–37. doi:10.3816/CLC.2011.n.004.
  • Hoang T, Campbell TC, Zhang C, Kim K, Kolesar JM, KR O, JH B, Robinson EG, Ahuja HG, Kirschling RJ, et al. Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: A wisconsin oncology network phase II study. Invest New Drugs. 2014;32:195–199. doi:10.1007/s10637-013-9980-5.
  • Zhao Y, Foster NR, Meyers JP, Thomas SP, Northfelt DW, Rowland KM, Mattar BI, Johnson DB, Molina JR, Mandrekar SJ, et al. A phase I/II study of bortezomib in combination with paclitaxel, carboplatin, and concurrent thoracic radiation therapy for non-small-cell lung cancer: North Central Cancer Treatment Group (NCCTG)-N0321. J Thorac Oncol. 2015;10:172–180. doi:10.1097/JTO.0000000000000383.
  • Kontopodis E, Kotsakis A, Kentepozidis N, Syrigos K, Ziras N, Moutsos M, Filippa G, Mala A, Vamvakas L, Mavroudis D, et al. A phase II, open-label trial of bortezomib (VELCADE®) in combination with gemcitabine and cisplatin in patients with locally advanced or metastatic non-small cell lung cancer. Cancer Chemother Pharmacol. 2016;77:949–956. doi:10.1007/s00280-016-2997-7.
  • Davies AM, Chansky K, Lara PN, Gumerlock PH, Crowley J, Albain KS, Vogel SJ, Gandara DR. 2009. Bortezomib plus gemcitabine/carboplatin as first-line treatment of advanced non-small cell lung cancer: A phase II southwest oncology group study (S0339). J Thorac Oncol. 4:87–92. doi:10.1097/JTO.0b013e3181915052.
  • Piperdi B, Walsh WV, Bradley K, Zhou Z, Bathini V, Hanrahan-Boshes M, Hutchinson L, Perez-Soler R. 2012. Phase-I/II study of bortezomib in combination with carboplatin and bevacizumab as first-line therapy in patients with advanced non-small-cell lung cancer. J Thorac Oncol. 7:1032–1040. doi:10.1097/JTO.0b013e31824de2fa.
  • Li T, Ho L, Piperdi B, Elrafei T, Camacho FJ, Rigas JR, Perez-Soler R, Gucalp R. 2010. Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade®) in chemotherapy-naïve patients with advanced stage non-small cell lung cancer (NSCLC). Lung Cancer. 68:89–93. doi:10.1016/j.lungcan.2009.05.009.
  • Besse B, Planchard D, Veillard A-S, Taillade L, Khayat D, Ducourtieux M, Pignon J-P, Lumbroso J, Lafontaine C, Mathiot C, et al. Phase 2 study of frontline bortezomib in patients with advanced non-small cell lung cancer. Lung Cancer. 2012;76:78–83. doi:10.1016/j.lungcan.2011.09.006.
  • Lara PN, Chansky K, Davies AM, Franklin WA, Gumerlock PH, Guaglianone PP, Atkins JN, Farneth N, Mack PC, Crowley JJ, et al. Bortezomib (PS-341) in relapsed or refractory extensive stage small cell lung cancer: A Southwest oncology group phase II trial (S0327). J Thorac Oncol. 2006;1:996–1001. doi:10.1097/01243894-200611000-00013.
  • Ramalingam SS, Davies AM, Longmate J, Edelman MJ, Lara PN, Vokes EE, Villalona-Calero M, Gitlitz B, Reckamp K, Salgia R, et al. Bortezomib for patients with advanced-stage bronchioloalveolar carcinoma: A California cancer consortium phase II study (NCI 7003). J Thorac Oncol. 2011;6:1741–1745. doi:10.1097/JTO.0b013e318225924c.
  • Drilon A, Schoenfeld AJ, Arbour KC. Exceptional responders with invasive mucinous adenocarcinomas: a phase 2 trial of bortezomib in patients with KRAS G12D-mutant lung cancers. Cold Spring Harb Mol Case Stud. 2019;5. doi:10.1101/mcs.a003665.
  • Papadopoulos KP, Burris HA, Gordon M, Lee P, Sausville EA, Rosen PJ, Patnaik A, Cutler RE, Wang Z, Lee S, et al. A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013;72:861–868. doi:10.1007/s00280-013-2267-x.
  • National Institutes of Health. Clinical Trials.Gov. [accessed 2019 Jun 12]. https://clinicaltrials.gov/ct2/results?cond=Lung+Cancer&term=Carfilzomib&cntry=&state=&city=&dist=.
  • Taylor D, Koch WM, Zahurak M, Shah K, Sidransky D, Westra WH. Immunohistochemical detection of p53 protein accumulation in head and neck cancer: correlation with p53 gene alterations. Hum Pathol. 1999 Oct;30:1221–1225. doi:10.1016/s0046-8177(99)90041-2.