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Commentary

Small molecule drugs with immunomodulatory effects in cancer

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Pages 2463-2468 | Received 05 May 2015, Accepted 28 May 2015, Published online: 16 Sep 2015

References

  • Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. New Engl J Med 2011; 364:2517-26; PMID:21639810; http://dx.doi.org/10.1056/NEJMoa1104621
  • Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. New Engl J Med 2012; 366:2455-65; PMID:22658128; http://dx.doi.org/10.1056/NEJMoa1200694
  • Le DT, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, Morse M, Zeh H, Cohen D, Fine RL, et al. Safety and survival with GVAX pancreas prime and listeria monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol 2015; 33:1325-33; PMID:25584002; http://dx.doi.org/10.1200/JCO.2014.57.4244
  • Hoelder S, Clarke PA, Workman P. Discovery of small molecule cancer drugs: successes, challenges and opportunities. Mol Oncol 2012; 6:155-76; PMID:22440008; http://dx.doi.org/10.1016/j.molonc.2012.02.004
  • Whittaker SJ, Demierre MF, Kim EJ, Rook AH, Lerner A, Duvic M, Scarisbrick J, Reddy S, Robak T, Becker JC, et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol 2010; 28:4485-91; PMID:20697094; http://dx.doi.org/10.1200/JCO.2010.28.9066
  • West AC, Mattarollo SR, Shortt J, Cluse LA, Christiansen AJ, Smyth MJ, Johnstone RW. An intact immune system is required for the anticancer activities of histone deacetylase inhibitors. Cancer Res 2013; 73:7265-76; PMID:24158093; http://dx.doi.org/10.1158/0008-5472.CAN-13-0890
  • Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 2009; 10:223-32; PMID:19230772; http://dx.doi.org/10.1016/S1470-2045(09)70003-8
  • Daurkin I, Eruslanov E, Vieweg J, Kusmartsev S. Generation of antigen-presenting cells from tumor-infiltrated CD11b myeloid cells with DNA demethylating agent 5-aza-2'-deoxycytidine. Cancer Immunol Immunotherapy 2010; 59:697-706; PMID:19882154; http://dx.doi.org/10.1007/s00262-009-0786-4
  • Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR, Eastern cooperative oncology G. phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the eastern cooperative oncology group. J Clin Oncol 2006; 24:431-6; PMID:16365178; http://dx.doi.org/10.1200/JCO.2005.03.0221
  • Eigentler TK, Kamin A, Weide BM, Breuninger H, Caroli UM, Mohrle M, Radny P, Garbe C. A phase III, randomized, open label study to evaluate the safety and efficacy of imiquimod 5% cream applied thrice weekly for 8 and 12 weeks in the treatment of low-risk nodular basal cell carcinoma. J Am Acad Dermatol 2007; 57:616-21; PMID:17610993; http://dx.doi.org/10.1016/j.jaad.2007.05.022
  • Schon MP, Schon M. Imiquimod: mode of action. British J Dermatol 2007; 157 2:8-13; http://dx.doi.org/10.1111/j.1365-2133.2007.08265.x
  • Huh JR, Littman DR. Small molecule inhibitors of RORgammat: targeting Th17 cells and other applications. Europ J Immunol 2012; 42:2232-7; PMID:22949321; http://dx.doi.org/10.1002/eji.201242740
  • Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003; 9:1269-74; PMID:14502282; http://dx.doi.org/10.1038/nm934
  • Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med 2005; 11:312-9; PMID:15711557; http://dx.doi.org/10.1038/nm1196
  • Prendergast GC. Immune escape as a fundamental trait of cancer: focus on IDO. Oncogene 2008; 27:3889-900; PMID:18317452; http://dx.doi.org/10.1038/onc.2008.35
  • Smith C, Chang MY, Parker KH, Beury DW, DuHadaway JB, Flick HE, Boulden J, Sutanto-Ward E, Soler AP, Laury-Kleintop LD, et al. IDO is a nodal pathogenic driver of lung cancer and metastasis development. Cancer Discov 2012; 2:722-35; PMID:22822050; http://dx.doi.org/10.1158/2159-8290.CD-12-0014
  • Witkiewicz A, Williams TK, Cozzitorto J, Durkan B, Showalter SL, Yeo CJ, Brody JR. Expression of indoleamine 2,3-dioxygenase in metastatic pancreatic ductal adenocarcinoma recruits regulatory T cells to avoid immune detection. J Am College Surgeons 2008; 206:849-54; discussion 54-6; PMID:18471709; http://dx.doi.org/10.1016/j.jamcollsurg.2007.12.014
  • Ferdinande L, Decaestecker C, Verset L, Mathieu A, Moles Lopez X, Negulescu AM, Van Maerken T, Salmon I, Cuvelier CA, Demetter P. Clinicopathological significance of indoleamine 2,3-dioxygenase 1 expression in colorectal cancer. British J Cancer 2012; 106:141-7; PMID:22108515; http://dx.doi.org/10.1038/bjc.2011.513
  • Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A, Fioretti MC, Puccetti P. T cell apoptosis by tryptophan catabolism. Cell Death Differentiation 2002; 9:1069-77; PMID:12232795; http://dx.doi.org/10.1038/sj.cdd.4401073
  • Munn DH, Sharma MD, Hou D, Baban B, Lee JR, Antonia SJ, Messina JL, Chandler P, Koni PA, Mellor AL. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest 2004; 114:280-90; PMID:15254595; http://dx.doi.org/10.1172/JCI200421583
  • Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clinical Investigation 2007; 117:2570-82; PMID:17710230; http://dx.doi.org/10.1172/JCI31911
  • Hou DY, Muller AJ, Sharma MD, DuHadaway J, Banerjee T, Johnson M, Mellor AL, Prendergast GC, Munn DH. Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses. Cancer Res 2007; 67:792-801; PMID:17234791; http://dx.doi.org/10.1158/0008-5472.CAN-06-2925
  • Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, Schumacher T, Jestaedt L, Schrenk D, Weller M, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 2011; 478:197-203; PMID:21976023; http://dx.doi.org/10.1038/nature10491
  • Soliman HH, Jackson E, Neuger T, Dees EC, Harvey RD, Han H, Ismail-Khan R, Minton S, Vahanian NN, Link C, et al. A first in man phase I trial of the oral immunomodulator, indoximod, combined with docetaxel in patients with metastatic solid tumors. Oncotarget 2014; 5:8136-46; PMID:25327557
  • Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood 2010; 115:3520-30; PMID:20197554; http://dx.doi.org/10.1182/blood-2009-09-246124
  • Beatty GL, O'Dwyer PJ, Clark J, Shi JG, Newton RC, Schaub R, Maleski J, Leopold L, Gajewski T. Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the oral inhibitor of indoleamine 2,3-dioxygenase (IDO1) INCB024360 in patients (pts) with advanced malignancies. J Clin Oncol 2013; 31 (suppl; abstr 3025).
  • Newton RC, Scherle PA, Bowman K, Liu X, Beatty GL, O'Dwyer PJ, Gajewski T, Bowman J, Schaub R, Leopold L. Pharmacodynamic assessment of INCB024360, an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), in advanced cancer patients. J Clin Oncol 30, 2012 (suppl; abstr 2500^)
  • Hiscox AG H, Couto J, Liao Z, Zhu Y, Liu X, Newton RC, Hnatyszyn J. Development of an IHC-based detection method for studying indoleamine 2,3-dioxygenase 1 (IDO1) expression in human cancers. 2014 ASCO annual meeting. J Clin Oncol 2014:5s 3043
  • Gibney GTHO, Gangadhar TC, Lutzky J, Olszanski AJ, Gajewski T, Chmielowski B, Boasberg PD, Zhao Y, Newton RC, Scherle PA, et al. Preliminary results from a phase 1/2 study of INCB024360 combined with ipilimumab (ipi) in patients (pts) with melanoma. J Clin Oncol 2014; 32:3010
  • Khleif SMD, Nyak-Kapoor A, Mautino MR, Kennedy E, Vahanian NN, Link CJ. First-in-human phase 1 study of the novel indoleamine-2,3-dioxygenase (IDO) inhibitor NLG-919. J Clin Oncol 2014; 32:5s:TPS3121
  • Iversen TZ, Engell-Noerregaard L, Ellebaek E, Andersen R, Larsen SK, Bjoern J, Zeyher C, Gouttefangeas C, Thomsen BM, Holm B, et al. Long-lasting disease stabilization in the absence of toxicity in metastatic lung cancer patients vaccinated with an epitope derived from indoleamine 2,3 dioxygenase. Clin Cancer Res 2014; 20:221; PMID:24218513; http://dx.doi.org/10.1158/1078-0432.CCR-13-1560
  • Roskoski R Jr. ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res 2012; 66:105-43; PMID:22569528; http://dx.doi.org/10.1016/j.phrs.2012.04.005
  • Prior IA, Lewis PD, Mattos C. A comprehensive survey of Ras mutations in cancer. Cancer Res 2012; 72:2457-67; PMID:22589270; http://dx.doi.org/10.1158/0008-5472.CAN-11-2612
  • Engel MA, Neurath MF. Anticancer properties of the IL-12 family–focus on colorectal cancer. Current Med Chem 2010; 17:3303-8; PMID:20712574; http://dx.doi.org/10.2174/092986710793176366
  • Puig-Kroger A, Relloso M, Fernandez-Capetillo O, Zubiaga A, Silva A, Bernabeu C, Corbi AL. Extracellular signal-regulated protein kinase signaling pathway negatively regulates the phenotypic and functional maturation of monocyte-derived human dendritic cells. Blood 2001; 98:2175-82; PMID:11568005; http://dx.doi.org/10.1182/blood.V98.7.2175
  • Arrighi JF, Rebsamen M, Rousset F, Kindler V, Hauser C. A critical role for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-α, and contact sensitizers. J Immunol 2001; 166:3837-45; PMID:11238627; http://dx.doi.org/10.4049/jimmunol.166.6.3837
  • Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, Demidov LV, Hassel JC, Rutkowski P, Mohr P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. New Engl J Med 2012; 367:107-14; PMID:22663011; http://dx.doi.org/10.1056/NEJMoa1203421
  • Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. New Engl J Med 2015; 372:30-9; PMID:25399551; http://dx.doi.org/10.1056/NEJMoa1412690
  • Bendell JCACE, André T, Tabernero J, Gordon MS, Bernards R, Van Cutsem E, Tejpar S, Sidhu R, Go WY, Allred A, et al. Efficacy and tolerability in an open-label phase I/II study of MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in combination in patients (pts) with BRAF V600E mutated colorectal cancer (CRC). J Clin Oncol 32:5s 2014 3515
  • Hochster HS, Uboha N, Messersmith W, Gold PJ, BH ON, Cohen D, Denlinger C, Cohen S, Leichman CG, Leichman L, et al. Phase II study of selumetinib (AZD6244, ARRY-142886) plus irinotecan as second-line therapy in patients with K-RAS mutated colorectal cancer. Cancer Chemotherapy Pharmacol 2015; 75:17-23; http://dx.doi.org/10.1007/s00280-014-2609-3
  • Do K, Speranza G, Bishop R, Khin S, Rubinstein L, Kinders RJ, Datiles M, Eugeni M, Lam MH, Doyle LA, et al. Biomarker-driven phase 2 study of MK-2206 and selumetinib (AZD6244, ARRY-142886) in patients with colorectal cancer. Investigational New Drugs 2015; 33(3): 720–8; PMID:25637165
  • Bekaii-Saab T, Phelps MA, Li X, Saji M, Goff L, Kauh JS, O'Neil BH, Balsom S, Balint C, Liersemann R, et al. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol 2011; 29:2357-63; PMID:21519026; http://dx.doi.org/10.1200/JCO.2010.33.9473
  • Finn RSJMM, Tan, BR, Weekes CD, Bendell JC; Patnaik A, Khan GN, Laheru D, Anderson L, Christy-Bittel JL, Barrett E et al. A phase I study of MEK inhibitor MEK162 (ARRY-438162) in patients with biliary tract cancer. 2010 ASCO GI conference. J Clin Oncol 2012:4 220
  • Van Cutsem EH, Bazin MI, Canon JL, Poddubskaya E, Manojlovic N, Milella M, Radenkovic D, Verslype C, Guo W, Damstrup L, et al. Phase II randomized trial of MEK inhibitor pimasertib or placebo combined with gemcitabine in the first-line treatment of metastatic pancreatic cancer. J Clin Oncol 2015; 33:3 344
  • Van Laethem JL, Jassem J, Heinemann V, Weekes CD, Bridgewater JA, Cascinu S, Melichar B, Peeters M, Ross PJ, Saramak P, Giurescu M, et al. Phase II study of refametinib (BAY 86-9766), an allosteric dual MEK 1/2 inhibitor, and gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer. J Clin Oncol 2014; 32 (suppl; abstr 4025).
  • Wang D, Boerner SA, Winkler JD, LoRusso PM. Clinical experience of MEK inhibitors in cancer therapy. Biochimica et Biophysica Acta 2007; 1773:1248-55; PMID:17194493; http://dx.doi.org/10.1016/j.bbamcr.2006.11.009
  • Renouf DJ, Velazquez-Martin JP, Simpson R, Siu LL, Bedard PL. Ocular toxicity of targeted therapies. J Clin Oncol 2012; 30:3277-86; PMID:22649132; http://dx.doi.org/10.1200/JCO.2011.41.5851
  • Chen X, Schwartz GK, DeAngelis LM, Kaley T, Carvajal RD. Dropped head syndrome: report of three cases during treatment with a MEK inhibitor. Neurology 2012; 79:1929-31; PMID:23077008; http://dx.doi.org/10.1212/WNL.0b013e318271f87e
  • Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CM, Queirolo P, Blank CU, Hauschild A, Beck JT, St-Pierre A, et al. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol 2013; 14:249-56; PMID:23414587; http://dx.doi.org/10.1016/S1470-2045(13)70024-X
  • Chen MH, Kerkela R, Force T. Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics. Circulation 2008; 118:84-95; PMID:18591451; http://dx.doi.org/10.1161/CIRCULATIONAHA.108.776831

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