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Perspective

Not the comfy chair! Cancer drugs that act against multiple active sites

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Pages 893-901 | Received 21 Oct 2019, Accepted 07 Nov 2019, Published online: 14 Nov 2019

References

  • Klaeger S, Heinzlmeir S, Wilhelm M, et al. The target landscape of clinical kinase drugs. Science. 2017;358:pii: eaan4368.
  • Muttathukattil AN, Srinivasan S, Halder A, et al. Role of guanidinium-carboxylate ion interaction in enzyme inhibition with implication for drug design. J Phys Chem B. 2019 Oct 9;123: 9302–9311.
  • Dobrydnev AV, Tkachuka TM, Atamaniuka VP, et al. Quercetin-amino acid conjugates are promising anti-cancer agents in drug discovery projects. Mini Rev Med Chem. 2019 Oct 9;19. DOI:10.2174/1389557519666191009152007.
  • Deeks ED. Neratinib: first global approval. Drugs. 2017;77:1695–1704.
  • Wilhelm S, Carter C, Lynch M, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5:835–844.
  • Inaba H, Panetta JC, Pounds S, et al. Sorafenib population pharmacokinetics and skin toxicities in children and adolescents with refractory/relapsed leukemia or solid tumor malignancies. Clin Cancer Res. 2019 Aug 27. pii: clincanres.0470.2019. doi: 10.1158/1078-0432.CCR-19-0470
  • Strumberg D, Voliotis D, Moeller JG, et al. Results of phase I pharmacokinetic and pharmacodynamic studies of the Raf kinase inhibitor BAY 43-9006 in patients with solid tumors. Int J Clin Pharmacol Ther. 2002;40:580–581.
  • Awada A, Hendlisz A, Gil T, et al. Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer. 2005;92:1855–1861.
  • Clark JW, Eder JP, Ryan D, et al. Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors. Clin Cancer Res. 2005;11:5472–5480.
  • Gavini J, Dommann N, Jakob MO, et al. Verteporfin-induced lysosomal compartment dysregulation potentiates the effect of sorafenib in hepatocellular carcinoma. Cell Death Dis. 2019;10:749.
  • Lin CH, Elkholy KH, Wani NA, et al. Ibrutinib potentiates anti-hepatocarcinogenic efficacy of sorafenib by targeting EGFR in tumor cells and BTK in immune cells in the stroma. Mol Cancer Ther. 2019 Oct 3. pii: molcanther.0135.2019. doi: 10.1158/1535-7163.MCT-19-0135
  • Wang C, Wang H, Lieftink C, et al. CDK12 inhibition mediates DNA damage and is synergistic with sorafenib treatment in hepatocellular carcinoma. Gut. 2019 Sep 13. pii: gutjnl-2019-318506. doi: 10.1136/gutjnl-2019-318506.
  • Takimoto CH, Awada A. Safety and anti-tumor activity of sorafenib (Nexavar) in combination with other anti-cancer agents: a review of clinical trials. Cancer Chemother Pharmacol. 2008;61:535–548.
  • Strumberg D, Clark JW, Awada A, et al. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist. 2007;12:426–437.
  • Flaherty KT, Schiller J, Schuchter LM, et al. A phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel. Clin Cancer Res. 2008;14:4836–4842.
  • Pan P, Wang L, Wang Y, et al. Systematic review and meta-analysis of -new-generation tyrosine kinase inhibitors versus imatinib for newly diagnosed chronic myeloid leukemia. Acta Haematol. 2019;12:1–13.
  • Fondevila F, Méndez-Blanco C, Fernández-Palanca P, et al. Anti-tumoral activity of single and combined regorafenib treatments in preclinical models of liver and gastrointestinal cancers. Exp Mol Med. 2019;51:109.
  • Lee ATJ, Jones RL, Huang PH. Pazopanib in advanced soft tissue sarcomas. Signal Transduct Target Ther. 2019;4:16.
  • Bæk MN, Budolfsen C, Grimm D, et al. Drug-induced hypertension caused by multikinase inhibitors (Sorafenib, sunitinib, lenvatinib and axitinib) in renal cell carcinoma treatment. Int J Mol Sci. 2019;20(19):4712. pii: E4712. doi: 10.3390/ijms20194712.
  • Brattås MK, Reikvam H, Tvedt THA, et al. Dasatinib as an investigational drug for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in adults. Expert Opin Investig Drugs. 2019;28:411–420.
  • Gross-Goupil M, Kwon TG, Eto M, et al. Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial. Ann Oncol. 2018;29:2371–2378.
  • Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64:7099–7109.
  • Carlomagno F, Anaganti S, Guida T, et al. BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst. 2006;98:326–334.
  • Chiou JF, Tai CJ, Huang MT, et al. Glucose-regulated protein 78 is a novel contributor to acquisition of resistance to sorafenib in hepatocellular carcinoma. Ann Surg Oncol. 2010;17:603–612.
  • Roberts JL, Tavallai M, Nourbakhsh A, et al. GRP78/Dna K is a target for nexavar/stivarga/votrient in the treatment of human malignancies, viral infections and bacterial diseases. J Cell Physiol. 2015;230:2552–2578.
  • Booth L, Shuch B, Albers T, et al. Multi-kinase inhibitors can associate with heat shock proteins through their NH2-termini by which they suppress chaperone function. Oncotarget. 2016;7:12975–12996.
  • Booth L, Roberts JL, Tavallai M, et al. OSU-03012 and viagra treatment inhibits the activity of multiple chaperone proteins and disrupts the blood-brain barrier: implications for anti-cancer therapies. J Cell Physiol. 2015;230:1982–1998.
  • Rahmani M, Davis EM, Crabtree TR, et al. The kinase inhibitor sorafenib induces cell death through a process involving induction of endoplasmic reticulum stress. Mol Cell Biol. 2007;27:5499–5513.
  • Park MA, Zhang G, Martin AP, et al. Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation. Cancer Biol Ther. 2008;7:1648–1662.
  • Zhu G, Lee AS. Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. J Cell Physiol. 2015;230:1413–1420.
  • Booth L, Roberts JL, Ecroyd H, et al. AR-12 inhibits multiple chaperones concomitant with stimulating autophagosome formation collectively preventing virus replication. J Cell Physiol. 2016;231:2286–2302.
  • NCT00978523. Study of AR-12 (2-Amino-N-[4-[5-(2 Phenanthrenyl)-3-(Trifluoromethyl)-1H-pyrazol-1-yl] Phenyl]-Acetamide) in Adult Patients With Advanced or Recurrent Solid Tumors or Lymphoma.
  • Verheijen RB, Beijnen JH, Schellens JHM, et al. Clinical pharmacokinetics and pharmacodynamics of pazopanib: towards optimized dosing. Clin Pharmacokinet. 2017;56:987–997.
  • Masood A, Kancha RK, Subramanian J. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer harboring uncommon EGFR mutations: focus on afatinib. Semin Oncol. 2019 Sep 11;46:271–283. pii: S0093-7754(18)30191-X.
  • Paranjpe R, Basatneh D, Tao G, et al. Neratinib in HER2-positive breast cancer patients. Ann Pharmacother. 2019;53:612–620.
  • Sooro MA, Zhang N, Zhang P. Targeting EGFR-mediated autophagy as a potential strategy for cancer therapy. Int J Cancer. 2018;143:2116–2125.
  • Liu Q, Yu S, Zhao W, et al. EGFR-TKIs resistance via EGFR-independent signaling pathways. Mol Cancer. 2018;17:53.
  • Moll HP, Pranz K, Musteanu M, et al. Afatinib restrains K-RAS-driven lung tumorigenesis. Sci Transl Med. 2018;10:eaao2301.
  • Yamaoka T, Ohmori T, Ohba M, et al. Distinct afatinib resistance mechanisms identified in lung adenocarcinoma harboring an EGFR mutation. Mol Cancer Res. 2017;15:915–928.
  • Ebert K, Mattes J, Kunzke T, et al. MET as resistance factor for afatinib therapy and motility driver in gastric cancer cells. PLoS One. 2019;14:e0223225.
  • Scaltriti M, Verma C, Guzman M, et al. Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene. 2009;28:803–814.
  • Collins DM, Gately K, Hughes C, et al. Tyrosine kinase inhibitors as modulators of trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity in breast cancer cell lines. Cell Immunol. 2017;319:35–42.
  • Collins DM, Conlon NT, Kannan S, et al. Preclinical characteristics of the irreversible pan-HER kinase inhibitor neratinib compared with lapatinib: implications for the treatment of HER2-positive and HER2-mutated breast cancer. Cancers (Basel). 2019;11:737. pii: E737.
  • Cocco E, Javier Carmona F, Razavi P, et al. Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2). PLoS One. 2018;13:e0200836.
  • Kwak EL, Sordella R, Bell DW, et al. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci U S A. 2005;102:7665–7670.
  • Zhang Y, Zhang J, Liu C, et al. Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells. Sci Signal. 2018;11. pii: eaat9773. DOI:10.1126/scisignal.aat9773.
  • Pal R, Wei N, Song N, et al. Molecular subtypes of colorectal cancer in pre-clinical models show differential response to targeted therapies: treatment implications beyond KRAS mutations. PLoS One. 2018;13:e0200836.
  • Kruspig B, Monteverde T, Neidler S, et al. The ERBB network facilitates KRAS-driven lung tumorigenesis. Sci Transl Med. 2018;10:eaao2565. pii: eaao2565.
  • Tavallai M, Booth L, Roberts JL, et al. Rationally repurposing ruxolitinib (Jakafi (®)) as a solid tumor therapeutic. Front Oncol. 2016;6:142.
  • Booth L, Roberts JL, Tavallai M, et al. The afatinib resistance of in vivo generated H1975 lung cancer cell clones is mediated by SRC/ERBB3/c-KIT/c-MET compensatory survival signaling. Oncotarget. 2016;7:19620–19630.
  • Booth L, Roberts JL, Poklepovic A, et al. HDAC inhibitors enhance neratinib activity and when combined enhance the actions of an anti-PD-1 immunomodulatory antibody in vivo. Oncotarget. 2017;8:90262–90277.
  • Davis MI, Hunt JP, Herrgard S, Ciceri P, et al.Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011;29:1046–1051.
  • Fuller SJ, McGuffin LJ, Marshall AK, et al. A novel non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3). Biochem J. 2012;442:595–610.
  • Klooster JP, Jansen M, Yuan J, et al. Mst4 and Ezrin induce brush borders downstream of the Lkb1/Strad/Mo25 polarization complex. Dev Cell. 2009;16:551–562.
  • Jang JW, Kim MK, Bae SC. Reciprocal regulation of YAP/TAZ by the hippo pathway and the small GTPase pathway. Small GTPases. 2018;20:1–9.
  • Rawat SJ, Chernoff J. Regulation of mammalian Ste20 (Mst) kinases. Tr Biochem Sci. 2015;40:149–156.
  • Bae SJ, Luo X. Activation mechanisms of the hippo kinase signaling cascade. Biosci Rep. 2018;38. pii: BSR20171469. DOI:10.1042/BSR20171469.
  • Kong D, Zhao Y, Men T, et al. Hippo signaling pathway in liver and pancreas: the potential drug target for tumor therapy. J Drug Target. 2015;23:125–133.
  • Patel SH, Camargo FD, Yimlamai D. Hippo signaling in the liver regulates organ size, cell fate, and carcinogenesis. Gastroenterology. 2017;152:533–545.
  • Hergovich A. The roles of NDR protein kinases in hippo signalling. Genes (Basel). 2016;7:21. pii: E21.
  • Sharif AAD, Hergovich A. The NDR/LATS protein kinases in immunology and cancer biology. Semin Cancer Biol. 2018;48:104–114.
  • Bitra A, Sistla S, Mariam J, et al. Rassf proteins as modulators of Mst1 kinase activity. Sci Rep. 2017;7:45020.
  • Chen M, Zhang H, Shi Z, et al. The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer. J Biol Chem. 2018;293:14455–14469.
  • Dent P, Booth L, Roberts JL, et al. Neratinib inhibits hippo/YAP signaling, reduces mutant K-RAS expression, and kills pancreatic and blood cancer cells. Oncogene. 2019;38:5890–5904.
  • Crawford JJ, Bronner SM, Zbieg JR. Hippo pathway inhibition by blocking the YAP/TAZ-TEAD interface: a patent review. Expert Opin Ther Pat. 2018;28:867–873.
  • Meng Z, Moroishi T, Mottier-Pavie V, et al. MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the hippo pathway. Nat Commun. 2015;6:8357.
  • Hergovich A. Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical hippo signalling. Cell Biosci. 2013;3:32.
  • Booth L, Roberts JL, Rais R, et al. Neratinib augments the lethality of [regorafenib + sildenafil]. J Cell Physiol. 2019 Apr;234(4):4874–4997.
  • Thompson BJ, Sahai E. MST kinases in development and disease. J Cell Biol. 2015;210:871–882.
  • Chen S, Fang Y, Xu S, et al. Mammalian Sterile20-like kinases: signalings and roles in central nervous system. Aging Dis. 2018;9:537–552.
  • Wang OH, Azizian N, Guo M, et al. Prognostic and functional significance of MAP4K5 in pancreatic cancer. PLoS One. 2016;11:e0152300.
  • Hsu CL, Lee EX, Gordon KL, et al. MAP4K3 mediates amino acid-dependent regulation of autophagy via phosphorylation of TFEB. Nat Commun. 2018;9:942.
  • Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review. JAMA. 2019;322:764–774.
  • Kim RY, Sterman DH, Haas AR. Malignant mesothelioma: has anything changed? Semin Respir Crit Care Med. 2019;40:347–360.
  • Frederickson AM, Arndorfer S, Zhang I, et al. Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. Immunotherapy. 2019;11:407–428.
  • Racanelli AC, Rothbart SB, Heyer CL, et al. Therapeutics by cytotoxic metabolite accumulation: pemetrexed causes ZMP accumulation, AMPK activation, and mammalian target of rapamycin inhibition. Cancer Res. 2009;69:5467–5474.
  • Rothbart SB, Racanelli AC, Moran RG. Pemetrexed indirectly activates the metabolic kinase AMPK in human carcinomas. Cancer Res. 2010;70:10299–10309.
  • Brooks HB, Meier TI, Geeganage S, et al. Characterization of a novel AICARFT inhibitor which potently elevates ZMP and has anti-tumor activity in murine models. Sci Rep. 2018;8:15458.
  • Booth L, Roberts JL, Poklepovic A, et al. PDE5 inhibitors enhance the lethality of pemetrexed through inhibition of multiple chaperone proteins and via the actions of cyclic GMP and nitric oxide. Oncotarget. 2017;8:1449–1468.
  • Tripathi DN, Chowdhury R, Trudel LJ, et al. Reactive nitrogen species regulate autophagy through ATM-AMPK-TSC2-mediated suppression of mTORC1. Proc Natl Acad Sci U S A. 2013;110:E2950–7.
  • Alers S, Wesselborg S, Stork B. ATG13: just a companion, or an executor of the autophagic program? Autophagy. 2014;10:944–956.
  • Booth L, Roberts JL, Poklepovic A, et al. [pemetrexed + sildenafil], via autophagy-dependent HDAC downregulation, enhances the immunotherapy response of NSCLC cells. Cancer Biol Ther. 2017;18:705–714.
  • Booth L, Roberts JL, Poklepovic A, et al. HDAC inhibitors enhance the immunotherapy response of melanoma cells. Oncotarget. 2017;8:83155–83170.
  • Booth L, Roberts JL, Poklepovic A, et al. Prior exposure of pancreatic tumors to [sorafenib + vorinostat] enhances the efficacy of an anti-PD-1 antibody. Cancer Biol Ther. 2019;20:109–121.
  • Mohanty R, Chowdhury CR, Arega S, et al. CAR T cell therapy: a new era for cancer treatment (Review). Oncol Rep. 2019. DOI:10.3892/or.2019.7335.
  • Leonetti A, Wever B, Mazzaschi G, et al. Molecular basis and rationale for combining immune checkpoint inhibitors with chemotherapy in non-small cell lung cancer. Drug Resist Updat. 2019;46:100644.
  • Terranova-Barberio M, Thomas S, Ali N, et al. HDAC inhibition potentiates immunotherapy in triple negative breast cancer. Oncotarget. 2017;8:114156–114172.
  • Dent P, Booth L, Poklepovic A, et al. Signaling alterations caused by drugs and autophagy. Cell Signal. 2019;64:109416.
  • Booth L, Roberts JL, Kirkwood J, et al. Unconventional approaches to modulating the immunogenicity of tumor cells. Adv Cancer Res. 2018;137:1–15.
  • Booth L, Roberts JL, Sander C, et al. The HDAC inhibitor AR42 interacts with pazopanib to kill trametinib/dabrafenib-resistant melanoma cells in vitro and in vivo. Oncotarget. 2017;8:16367–16386.
  • Booth L, Roberts JL, Tavallai M, et al. [Pemetrexed + zorafenib] lethality is increased by inhibition of ERBB1/2/3-PI3K-NFκB compensatory survival signaling. Oncotarget. 2016;7:23608–23632.
  • Heidecker G, Huleihel M, Cleveland JL, et al. Mutational activation of c-raf-1 and definition of the minimal transforming sequence. Mol Cell Biol. 1990;10:2503–2512.
  • Booth L, Roberts JL, Rais R, et al. Palbociclib augments neratinib killing of tumor cells that is further enhanced by HDAC inhibition. Cancer Biol Ther. 2019;20:157–168.

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