towards improved death receptor targeted therapy for ... - TI Pharma

towards improved death receptor targeted therapy for ... - TI Pharma towards improved death receptor targeted therapy for ... - TI Pharma

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TRAIL and Hsp90 inhibition A549 cells. In H460 cells, minimal TRAIL‐induced Akt phosphorylation is detectable despite the observation that the PI3K/Akt inhibitor LY294002 to some extent increased TRAIL‐ induced apoptosis. In resistant A549 cells, LY294002 co‐treatment enhanced TRAIL‐ induced apoptosis by 4‐fold. Thus, Akt could be a mediator of the 17‐AAG effect in NSCLC cells. Perifosine, an Akt inhibitor, was described to increase TRAIL‐R2 receptor expression and decrease the cellular FLICE‐inhibitory protein (cFLIP) in human lung cancer cell lines, enhancing caspase‐8 activation [32]. ERK has generally been linked to TRAIL‐induced proliferation [33;34]. The inhibition of ERK by PD098059 did hardly sensitize these NSCLC cells for TRAIL and thus is unlikely to contribute to 17‐AAG enhancement of apoptosis. Clinical trials using small molecule inhibitors of Hsp90, like 17‐AAG, 17‐DMAG, VER‐52269, CNF2024, and IPI‐504 are currently being conducted [35]. Based on our results and previous studies, targeting Hsp90 in combination with induction of apoptosis by TRAIL might be of therapeutic value in the treatment of NSCLC. Acknowledgements This research was performed within the framework of project T3‐112 and T3‐103 of the Dutch Top Institute Pharma. ‐ 95 ‐

Chapter 5 Reference List 1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60(5):277‐ 300. 2. Almasan A, Ashkenazi A. Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy. Cytokine Growth Factor Rev 2003; 14(3‐4):337‐348. 3. Kruyt FA. TRAIL and cancer therapy. Cancer Lett 2008; 263(1):14‐25. 4. Gonzalvez F, Ashkenazi A. New insights into apoptosis signaling by Apo2L/TRAIL. Oncogene 2010; 29(34):4752‐4765. 5. Forero‐Torres A, Shah J, Wood T, Posey J, Carlisle R, Copigneaux C et al. Phase I trial of weekly tigatuzumab, an agonistic humanized monoclonal antibody targeting death receptor 5 (DR5). Cancer Biother Radiopharm 2010; 25(1):13‐19. 6. Greco FA, Bonomi P, Crawford J, Kelly K, Oh Y, Halpern W et al. Phase 2 study of mapatumumab, a fully human agonistic monoclonal antibody which targets and activates the TRAIL receptor‐1, in patients with advanced non‐small cell lung cancer. Lung Cancer 2008; 61(1):82‐90. 7. Herbst RS, Kurzrock R, Hong DS, Valdivieso M, Hsu CP, Goyal L et al. A first‐in‐human study of conatumumab in adult patients with advanced solid tumors. Clin Cancer Res 2010; 16(23):5883‐5891. 8. Stegehuis JH, de Wilt LH, de Vries EG, Groen HJ, de Jong S, Kruyt FA. TRAIL receptor targeting therapies for non‐small cell lung cancer: current status and perspectives. Drug Resist Updat 2010; 13(1‐2):2‐15. 9. Eid MA, Lewis RW, Abdel‐Mageed AB, Kumar MV. Reduced response of prostate cancer cells to TRAIL is modulated by NFkappaB‐mediated inhibition of caspases and Bid activation. Int J Oncol 2002; 21(1):111‐117. 10. Kandasamy K, Srivastava RK. Role of the phosphatidylinositol 3'‐kinase/PTEN/Akt kinase pathway in tumor necrosis factor‐related apoptosis‐inducing ligand‐induced apoptosis in non‐small cell lung cancer cells. Cancer Res 2002; 62(17):4929‐4937. 11. Song JH, Tse MC, Bellail A, Phuphanich S, Khuri F, Kneteman NM et al. Lipid rafts and nonrafts mediate tumor necrosis factor related apoptosis‐inducing ligand induced apoptotic and non‐apoptotic signals in non small cell lung carcinoma cells. Cancer Res 2007; 67(14):6946‐6955. 12. Van Schaeybroeck S, Kelly DM, Kyula J, Stokesberry S, Fennell DA, Johnston PG et al. Src and ADAM‐17‐mediated shedding of transforming growth factor‐alpha is a mechanism of acute resistance to TRAIL. Cancer Res 2008; 68(20):8312‐8321. 13. Altieri DC. Coupling apoptosis resistance to the cellular stress response: the IAP‐Hsp90 connection in cancer. Cell Cycle 2004; 3(3):255‐256. 14. Gallegos Ruiz MI, Floor K, Roepman P, Rodriguez JA, Meijer GA, Mooi WJ et al. Integration of gene dosage and gene expression in non‐small cell lung cancer, identification of HSP90 as potential target. PLoS One 2008; 3(3):e0001722. 15. Zuehlke A, Johnson JL. Hsp90 and co‐chaperones twist the functions of diverse client proteins. Biopolymers 2010; 93(3):211‐217. 16. Nguyen DM, Chen A, Mixon A, Schrump DS. Sequence‐dependent enhancement of paclitaxel toxicity in non‐small cell lung cancer by 17‐allylamino 17‐ demethoxygeldanamycin. J Thorac Cardiovasc Surg 1999; 118(5):908‐915. 17. Bijnsdorp IV, Kruyt FA, Gokoel S, Fukushima M, Peters GJ. Synergistic interaction between trifluorothymidine and docetaxel is sequence dependent. Cancer Sci 2008; 99(11):2302‐ 2308. 18. Wang X, Ju W, Renouard J, Aden J, Belinsky SA, Lin Y. 17‐allylamino‐17‐ demethoxygeldanamycin synergistically potentiates tumor necrosis factor‐induced lung cancer cell death by blocking the nuclear factor‐kappaB pathway. Cancer Res 2006; 66(2):1089‐1095. ‐ 96 ‐

Chapter 5<br />

Reference List<br />

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60(5):277‐<br />

300.<br />

2. Almasan A, Ashkenazi A. Apo2L/TRAIL: apoptosis signaling, biology, and potential <strong>for</strong><br />

cancer <strong>therapy</strong>. Cytokine Growth Factor Rev 2003; 14(3‐4):337‐348.<br />

3. Kruyt FA. TRAIL and cancer <strong>therapy</strong>. Cancer Lett 2008; 263(1):14‐25.<br />

4. Gonzalvez F, Ashkenazi A. New insights into apoptosis signaling by Apo2L/TRAIL. Oncogene<br />

2010; 29(34):4752‐4765.<br />

5. Forero‐Torres A, Shah J, Wood T, Posey J, Carlisle R, Copigneaux C et al. Phase I trial of<br />

weekly tigatuzumab, an agonistic humanized monoclonal antibody targeting <strong>death</strong><br />

<strong>receptor</strong> 5 (DR5). Cancer Biother Radiopharm 2010; 25(1):13‐19.<br />

6. Greco FA, Bonomi P, Craw<strong>for</strong>d J, Kelly K, Oh Y, Halpern W et al. Phase 2 study of<br />

mapatumumab, a fully human agonistic monoclonal antibody which targets and activates<br />

the TRAIL <strong>receptor</strong>‐1, in patients with advanced non‐small cell lung cancer. Lung Cancer<br />

2008; 61(1):82‐90.<br />

7. Herbst RS, Kurzrock R, Hong DS, Valdivieso M, Hsu CP, Goyal L et al. A first‐in‐human study<br />

of conatumumab in adult patients with advanced solid tumors. Clin Cancer Res 2010;<br />

16(23):5883‐5891.<br />

8. Stegehuis JH, de Wilt LH, de Vries EG, Groen HJ, de Jong S, Kruyt FA. TRAIL <strong>receptor</strong><br />

targeting therapies <strong>for</strong> non‐small cell lung cancer: current status and perspectives. Drug<br />

Resist Updat 2010; 13(1‐2):2‐15.<br />

9. Eid MA, Lewis RW, Abdel‐Mageed AB, Kumar MV. Reduced response of prostate cancer<br />

cells to TRAIL is modulated by NFkappaB‐mediated inhibition of caspases and Bid<br />

activation. Int J Oncol 2002; 21(1):111‐117.<br />

10. Kandasamy K, Srivastava RK. Role of the phosphatidylinositol 3'‐kinase/PTEN/Akt kinase<br />

pathway in tumor necrosis factor‐related apoptosis‐inducing ligand‐induced apoptosis in<br />

non‐small cell lung cancer cells. Cancer Res 2002; 62(17):4929‐4937.<br />

11. Song JH, Tse MC, Bellail A, Phuphanich S, Khuri F, Kneteman NM et al. Lipid rafts and<br />

nonrafts mediate tumor necrosis factor related apoptosis‐inducing ligand induced<br />

apoptotic and non‐apoptotic signals in non small cell lung carcinoma cells. Cancer Res<br />

2007; 67(14):6946‐6955.<br />

12. Van Schaeybroeck S, Kelly DM, Kyula J, Stokesberry S, Fennell DA, Johnston PG et al. Src<br />

and ADAM‐17‐mediated shedding of trans<strong>for</strong>ming growth factor‐alpha is a mechanism of<br />

acute resistance to TRAIL. Cancer Res 2008; 68(20):8312‐8321.<br />

13. Altieri DC. Coupling apoptosis resistance to the cellular stress response: the IAP‐Hsp90<br />

connection in cancer. Cell Cycle 2004; 3(3):255‐256.<br />

14. Gallegos Ruiz MI, Floor K, Roepman P, Rodriguez JA, Meijer GA, Mooi WJ et al. Integration<br />

of gene dosage and gene expression in non‐small cell lung cancer, identification of HSP90<br />

as potential target. PLoS One 2008; 3(3):e0001722.<br />

15. Zuehlke A, Johnson JL. Hsp90 and co‐chaperones twist the functions of diverse client<br />

proteins. Biopolymers 2010; 93(3):211‐217.<br />

16. Nguyen DM, Chen A, Mixon A, Schrump DS. Sequence‐dependent enhancement of<br />

paclitaxel toxicity in non‐small cell lung cancer by 17‐allylamino 17‐<br />

demethoxygeldanamycin. J Thorac Cardiovasc Surg 1999; 118(5):908‐915.<br />

17. Bijnsdorp IV, Kruyt FA, Gokoel S, Fukushima M, Peters GJ. Synergistic interaction between<br />

trifluorothymidine and docetaxel is sequence dependent. Cancer Sci 2008; 99(11):2302‐<br />

2308.<br />

18. Wang X, Ju W, Renouard J, Aden J, Belinsky SA, Lin Y. 17‐allylamino‐17‐<br />

demethoxygeldanamycin synergistically potentiates tumor necrosis factor‐induced lung<br />

cancer cell <strong>death</strong> by blocking the nuclear factor‐kappaB pathway. Cancer Res 2006;<br />

66(2):1089‐1095.<br />

‐ 96 ‐

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