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Farnesyltransferase Inhibitors as Anticancer Agents

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Oncogene-Directed Therapies

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

The long awaited molecular age of cancer diagnostics and pharmaceuticals is arriving at last, and it is fitting that drugs designed to interfere in the function of Ras, the first oncogenic protein found in human tumors, are leading the way. One class of such drugs, farnesyltransferase inhibitors (FTIs), illustrate both the promise and the cautions that accompany such molecularly targeted therapies. On one hand, FTIs represent a class of rationally designed drugs targeting the farnesyltransferase (FTase) enzyme that posttranslationally modifes Ras and other farnesylated proteins, and they have shown some efficacy in clinical trials as anticancer agents. On the other hand, several surprises have accompanied the development of FTIs, the most important of which is that FTIs do not inhibit Ras function primarily; indeed, the ultimate downstream targets of FTase inhibition are yet to be identified. This review describes the development of FTIs as anti-Ras and anticancer treatments, from both a basic and a translational science perspective, ending with a discussion of present understanding and future prospects for this novel class of therapeutic agents.

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References

  1. Shields JM, Pruitt K, McFall A, Shaub A, Der CJ. Understanding Ras: `it ain’t over ‘til it’s over’. Trends Cell Biol 2000; 10: 147–154.

    Article  PubMed  CAS  Google Scholar 

  2. Cox AD, Der CJ. Farnesyltransferase inhibitors and cancer treatment: targeting simply Ras? Biochim Biophys Acta 1997; 1333: F51 - F71.

    PubMed  CAS  Google Scholar 

  3. Shirasawa S, Furuse M, Yokoyama N, Sasazuki T. Altered growth of human colon cancer cell lines disrupted at activated Ki-ras. Science 1993; 260: 85–88.

    Article  PubMed  CAS  Google Scholar 

  4. Plattner R, Anderson MJ, Sato KY, Fasching CL, Der CJ, Stanbridge EJ. Loss of oncogenic ras expression does not correlate with loss of tumorigenicity in human cells. Proc Nail Acad Sci USA 1996; 93: 6665–6670.

    Article  CAS  Google Scholar 

  5. Chin L, Pomerantz J, Polsky D, Jacobson M, Cohen C, Cordon-Cardo C, et al. Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Genes Dev 1997; 11: 2822–2834.

    Article  PubMed  CAS  Google Scholar 

  6. Casey PJ, Solski PA, Der CJ, Buss JE. p2lras is modified by a farnesyl isoprenoid. Proc Natl Acad Sci USA 1989; 86: 8323–8327.

    Article  PubMed  CAS  Google Scholar 

  7. Schafer WR, Kim R, Sterne R, Thorner J, Kim SH, Rine J. Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans. Science 1989; 245: 379–385.

    Article  PubMed  CAS  Google Scholar 

  8. Schaber MD, O’Hara MB, Garsky VM, Mosser SC, Bergstrom JD, Moores SL, et al. Polyisoprenylation of Ras in vitro by a farnesyl-protein transferase. JBiol Chem 1990; 265: 14701–14704.

    CAS  Google Scholar 

  9. Glomset JA, Gelb MH, Farnsworth CC. Prenyl proteins in eukaryotic cells: a new type of membrane anchor. Trends Biochem Sci 1990; 15: 139–142.

    Article  PubMed  CAS  Google Scholar 

  10. Maltese WA. Posttranslational modification of proteins by isoprenoids in mammalian cells. Faseb J 1990; 4: 3319–3328.

    PubMed  CAS  Google Scholar 

  11. Zhang FL, Casey Pi. Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 1996; 65: 241–269.

    Article  PubMed  CAS  Google Scholar 

  12. Manne V, Roberts D, Tobin A, O’Rourke E, De Virgilio M, Meyers C, et al. Identification and preliminary characterization of protein-cysteine farnesyltransferase. Proc Natl Acad Sci USA 1990; 87: 7541–7545.

    Article  PubMed  CAS  Google Scholar 

  13. Reiss Y, Goldstein JL, Seabra MC, Casey PJ, Brown MS. Inhibition of purified p2lras farnesyl:protein transferase by Cys-AAX tetrapeptides. Cell 1990; 62: 81–88.

    Article  PubMed  CAS  Google Scholar 

  14. Gibbs JB. Ras C-terminal processing enzymes-new drug targets? Cell 1991; 65: 1–4.

    Article  PubMed  CAS  Google Scholar 

  15. Gibbs JB, Oliff A, Kohl NE. Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic. Cell 1994; 77: 175–178.

    Article  PubMed  CAS  Google Scholar 

  16. Gelb MH, Scholten JD, Sebolt-Leopold JS. Protein prenylation: from discovery to prospects for cancer treatment. Curr Opin Chem Biol 1998; 2: 40–48.

    Article  PubMed  CAS  Google Scholar 

  17. Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol 1999; 17: 3631–3652.

    PubMed  CAS  Google Scholar 

  18. Oliff A. Farnesyltransferase inhibitors: targeting the molecular basis of cancer. Biochim Biophys Acta 1999; 1423: C19 - C30.

    PubMed  CAS  Google Scholar 

  19. Sebti SM, Hamilton AD. Farnesyltransferase and geranylgeranyltransferase I inhibitors in cancer therapy: important mechanistic and bench to bedside issues. Expert Opin Investing Drugs 2000; 9: 2767–2782.

    Article  CAS  Google Scholar 

  20. Sepp-Lorenzino L, Ma Z, Rands E, Kohl NE, Gibbs JB, Oliff A, et al. A peptidomimetic inhibitor of farnesyl:protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines. Cancer Res 1995; 55: 5302–5309.

    PubMed  CAS  Google Scholar 

  21. Prendergast GC, Davide JP, deSolms SJ, Giuliani EA, Graham SL, Gibbs JB, et al. Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton. Mol Cell Biol 1994; 14: 4193–4202.

    PubMed  CAS  Google Scholar 

  22. Cox AD, Garcia AM, Westwick JK, Kowalczyk JJ, Lewis MD, Brenner DA, et al. The CAAX peptidomimetic compound B581 specifically blocks farnesylated, but not geranylgeranylated or myristylated, oncogenic ras signaling and transformation. JBiol Chem 1994; 269: 19203–19206.

    CAS  Google Scholar 

  23. Lerner EC, Zhang TT, Knowles DB, Qian Y, Hamilton AD, Sebti SM. Inhibition of the prenylation of K-Ras, but not H- or N-Ras, is highly resistant to CAAX peptidomimetics and requires both a farnesyltransferase and a geranylgeranyltransferase I inhibitor in human tumor cell lines. Oncogene 1997; 15: 1283–1288.

    Article  PubMed  CAS  Google Scholar 

  24. Whyte DB, Kirschmeier P, Hockenberry TN, Nunez-Oliva I, James L, Catino JJ, et al. K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J Biol Chem 1997; 272: 14459–14464.

    Article  PubMed  CAS  Google Scholar 

  25. Zhang FL, Kirschmeier P, Carr D, James L, Bond RW, Wang L, et al. Characterization of Ha-ras, N-ras, Ki-Ras4A, and Ki-Ras4B as in vitro substrates for farnesyl protein transferase and geranylgeranyl protein transferase type I. J Biol Chem 1997; 272: 10232–10239.

    Article  PubMed  CAS  Google Scholar 

  26. Rowell CA, Kowalczyk JJ, Lewis MD, Garcia AM. Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo. J Biol Chem 1997; 272: 14093–14097.

    Article  PubMed  CAS  Google Scholar 

  27. James G, Goldstein JL, Brown MS. Resistance of K-RasBV12 proteins to farnesyltransferase inhibitors in Ratl cells. Proc Natl Acad Sci USA 1996; 93: 4454–4458.

    Article  PubMed  CAS  Google Scholar 

  28. Sepp-Lorenzino L, Rosen N. A farnesyl-protein transferase inhibitor induces p21 expression and GI block in p53 wild type tumor cells. J Biol Chem 1998; 273: 20243–20251.

    Article  PubMed  CAS  Google Scholar 

  29. Ashar HR, James L, Gray K, Carr D, McGuirk M, Maxwell E, et al. The farnesyl transferase inhibitor SCH 66336 induces a G(2) M or G(1) pause in sensitive human tumor cell lines. Exp Cell Res 2001; 262: 17–27.

    Article  PubMed  CAS  Google Scholar 

  30. Nagasu T, Yoshimatsu K, Rowell C, Lewis MD, Garcia AM. Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956. Cancer Res 1995; 55: 5310–5314.

    PubMed  CAS  Google Scholar 

  31. Feldkamp MM, Lau N, Roncari L, Guha A. Isotype-specific Ras. GTP-levels predict the efficacy of farnesyl transferase inhibitors against human astrocytomas regardless of Ras mutational status. Cancer Res 2001; 61: 4425–4431.

    PubMed  CAS  Google Scholar 

  32. Lebowitz PF, Prendergast GC. Non-Ras targets of farnesyltransferase inhibitors: focus on Rho. Oncogene 1998; 17: 1439–1445.

    Article  PubMed  CAS  Google Scholar 

  33. Jahner D, Hunter T. The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts. Mol Cell Biol 1991; 11: 3682–3690.

    PubMed  CAS  Google Scholar 

  34. Adamson P, Marshall CJ, Hall A, Tilbrook PA. Post-translational modifications of p21rho proteins. J Biol Chem 1992; 267: 20033–20038.

    PubMed  CAS  Google Scholar 

  35. Armstrong SA, Hannah VC, Goldstein JL, Brown MS. CAAX geranylgeranyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB. J Biol Chem 1995; 270: 7864–7868.

    Article  PubMed  CAS  Google Scholar 

  36. Du W, Prendergast GC. Geranylgeranylated RhoB mediates suppression of human tumor cell growth by farnesyltransferase inhibitors. Cancer Res 1999; 59: 5492–5496.

    PubMed  CAS  Google Scholar 

  37. Liu A, Du W, Liu JP, Jessell TM, Prendergast GC. RhoB alteration is necessary for apoptotic and antineoplastic responses to farnesyltransferase inhibitors. Mol Cell Biol 2000; 20: 6105–6113.

    Article  PubMed  CAS  Google Scholar 

  38. Chen Z, Sun J, Pradines A, Favre G, Adnane J, Sebti SM. Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice. J Biol Chem 2000; 275: 17974–17978.

    Article  PubMed  CAS  Google Scholar 

  39. Miguel K, Pradines A, Sun J, Qian Y, Hamilton AD, Sebti SM, et al. GGTI-298 induces G0-G 1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells. Cancer Res 1997; 57: 1846–1850.

    Google Scholar 

  40. Song SY, Meszoely IM, Coffey RJ, Pietenpol JA, Leach SD. K-Ras-independent effects of the farnesyl transferase inhibitor L-744,832 on cyclin B1/Cdc2 kinase activity, G2/M cell cycle progression and apoptosis in human pancreatic ductal adenocarcinoma cells. Neoplasia 2000; 2: 261–272.

    Article  PubMed  CAS  Google Scholar 

  41. Ashar HR, James L, Gray K, Carr D, Black S, Armstrong L, et al. Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. J Biol Chem 2000; 275: 30451–30457.

    Article  PubMed  CAS  Google Scholar 

  42. Crespo NC, Ohkanda J, Yen TJ, Hamilton AD, Sebti SM. The farnesyltransferase inhibitor, FTI-2153, blocks bipolar spindle formation and chromosome alignment and causes prometaphase accumulation during mitosis of human lung cancer cells. J Biol Chem 2001; 276: 16161–16167.

    Article  PubMed  CAS  Google Scholar 

  43. Barrington RE, Subler MA, Rands E, Omer CA, Miller PJ, Hundley JE, et al. A farnesyltransferase inhibitor induces tumor regression in transgenic mice harboring multiple oncogenic mutations by mediating alterations in both cell cycle control and apoptosis. Mol Cell Biol 1998; 18: 85–92.

    PubMed  CAS  Google Scholar 

  44. Lebowitz PF, Sakamuro D, Prendergast GC. Farnesyl transferase inhibitors induce apoptosis of Ras-transformed cells denied substratum attachment. Cancer Res 1997; 57: 708–713.

    PubMed  CAS  Google Scholar 

  45. Suzuki N, Urano J, Tamanoi F. Farnesyltransferase inhibitors induce cytochrome c release and caspase 3 activation preferentially in transformed cells. Proc Natl Acad Sci USA 1998; 95: 15356–15361.

    Article  PubMed  CAS  Google Scholar 

  46. Du W, Liu A, Prendergast GC. Activation of the P13’K-AKT pathway masks the proapoptotic effects of farnesyltransferase inhibitors. Cancer Res 1999; 59: 4208–4212.

    PubMed  CAS  Google Scholar 

  47. Jiang K, Coppola D, Crespo NC, Nicosia SV, Hamilton AD, Sebti SM, et al. The phosphoinositide 3-OH kinase/AKT2 pathway as a critical target for farnesyltransferase inhibitor-induced apoptosis. Mol Cell Biol 2000; 20: 139–148.

    Article  PubMed  Google Scholar 

  48. Edamatsu H, Gau CL, Nemoto T, Guo L, Tamanoi F. Cdk inhibitors, roscovitine and olomoucine, synergize with farnesyltransferase inhibitor (FTI) to induce efficient apoptosis of human cancer cell lines. Oncogene 2000; 19: 3059–3068.

    Article  PubMed  CAS  Google Scholar 

  49. Kim KW, Chung HH, Chung CW, Kim IK, Miura M, Wang S, et al. Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: cleavage of the common alpha subunit during apoptosis. Oncogene 2001; 20: 358–366.

    Article  PubMed  CAS  Google Scholar 

  50. Kohl NE, Omer CA, Conner MW, Anthony NJ, Davide JP, deSolms Si, et al. Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nat Med 1995; 1: 792–797.

    Article  PubMed  CAS  Google Scholar 

  51. Liu M, Bryant MS, Chen J, Lee S, Yaremko B, Lipari P, et al. Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res 1998; 58: 4947–4956.

    PubMed  CAS  Google Scholar 

  52. Mangues R, Corral T, Kohl NE, Symmans WF, Lu S, Malumbres M, et al. Antitumor effect of a farnesyl protein transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice. Cancer Res 1998; 58: 1253–1259.

    PubMed  CAS  Google Scholar 

  53. Omer CA, Chen Z, Diehl RE, Conner MW, Chen HY, Trumbauer ME, et al. Mouse mammary tumor virus-Ki-rasB transgenic mice develop mammary carcinomas that can be growth-inhibited by a farnesyl:protein transferase inhibitor. Cancer Res 2000; 60: 2680–2688.

    PubMed  CAS  Google Scholar 

  54. Charvat S, Duchesne M, Parvaz P, Chignol MC, Schmitt D, Serres M. The up-regulation of vascular endothelial growth factor in mutated Ha-ras HaCaT cell lines is reduced by a farnesyl transferase inhibitor. Anticancer Res 1999; 19: 557–561.

    PubMed  CAS  Google Scholar 

  55. Kerbel RS, Viloria-Petit A, Klement G, Rak J. `Accidental’ anti-angiogenic drugs. anti-oncogene directed signal transduction inhibitors and conventional chemotherapeutic agents as examples. Eur J Cancer 2000; 36: 1248–1257.

    CAS  Google Scholar 

  56. Gu WZ, Tahir SK, Wang YC, Zhang HC, Cherian SP, O’Connor S, et al. Effect of novel CAAX peptidomimetic farnesyltransferase inhibitor on angiogenesis in vitro and in vivo. Eur J Cancer 1999; 35: 1394–1401.

    Article  PubMed  CAS  Google Scholar 

  57. Feldkamp MM, Lau N, Rak J, Kerbel RS, Guha A. Normoxic and hypoxic regulation of vascular endothelial growth factor (VEGF) by astrocytoma cells is mediated by Ras. Int J Cancer 1999; 81: 118–124.

    Article  PubMed  CAS  Google Scholar 

  58. Feldkamp MM, Lau N, Guha A. Growth inhibition of astrocytoma cells by farnesyl transferase inhibitors is mediated by a combination of anti-proliferative, pro-apoptotic and anti-angiogenic effects. Oncogene 1999; 18: 7514–7526.

    Article  PubMed  CAS  Google Scholar 

  59. Cohen-Jonathan E, Evans SM, Koch CJ, Muschel RJ, McKenna WG, Wu J, et al. The farnesyltransferase inhibitor L744,832 reduces hypoxia in tumors expressing activated H-ras. Cancer Res 2001; 61: 2289–2293.

    PubMed  CAS  Google Scholar 

  60. Petit T, Izbicka E, Lawrence RA, Bishop WR, Weitman S, Von Hoff DD. Activity of SCH 66336, a tricyclic farnesyltransferase inhibitor, against human tumor colony-forming units. Ann Oncol 1999; 10: 449–453.

    Article  PubMed  CAS  Google Scholar 

  61. Cox AD. Farnesyltransferase inhibitors: potential role in the treatment of cancer. Drugs 2001; 61: 723–732.

    Article  PubMed  CAS  Google Scholar 

  62. Zujewski J, Horak ID, Bol CJ, Woestenborghs R, Bowden C, End DW, et al. Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer. J Clin Oncol 2000; 18: 927–941.

    PubMed  CAS  Google Scholar 

  63. Adjei AA, Erlichman C, Davis JN, Cutler DL, Sloan JA, Marks RS, et al. A Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity. Cancer Res 2000; 60: 1871–1877.

    PubMed  CAS  Google Scholar 

  64. Hunt JT, Ding CZ, Batorsky R, Bednarz M, Bhide R, Cho Y, et al. Discovery of (R)-7-cyano-2,3,4, 5tetrahydro- 1-(1H-imidazol-4-ylmethyl)–3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine (BMS-214662), a farnesyltransferase inhibitor with potent preclinical antitumor activity. J Med Chem 2000; 43: 3587–3595.

    Article  PubMed  CAS  Google Scholar 

  65. Adjei AA, Davis JN, Erlichman C, Svingen PA, Kaufmann SH. Comparison of potential markers of farnesyltransferase inhibition. Clin Cancer Res 2000; 6: 2318–2325.

    PubMed  CAS  Google Scholar 

  66. Peters DG, Hoover RR, Gerlach MJ, Koh EY, Zhang H, Choe K, et al. Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. Blood 2001; 97: 1404–1412.

    Article  PubMed  CAS  Google Scholar 

  67. Karp JE. Farnesyl protein transferase inhibitors as targeted therapies for hematologic malignancies. Semis Hematol 2001; 38: 16–23.

    Article  CAS  Google Scholar 

  68. Karp JE, Lancet JE, Kaufmann SH, End DW, Wright JJ, Bol K, et al. Clinical and biologic activity of the farnesyltransferase inhibitor Rl 15777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial. Blood 2001; 97: 3361–3369.

    Article  PubMed  CAS  Google Scholar 

  69. Sun J, Blaskovich MA, Knowles D, Qian Y, Ohkanda J, Bailey RD, et al. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res 1999; 59: 4919–4926.

    PubMed  CAS  Google Scholar 

  70. Adjei AA, Davis JN, Bruzek LM, Erlichman C, Kaufmann SH. Synergy of the protein farnesyltransferase inhibitor SCH66336 and cisplatin in human cancer cell lines. Clin Cancer Res 2001; 7: 1438–1445.

    PubMed  CAS  Google Scholar 

  71. Moasser MM, Sepp-Lorenzino L, Kohl NE, Oliff A, Balog A, Su DS, et al. Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to taxol and epothilones. Proc Natl Acad Sci USA 1998; 95: 1369–1374.

    Article  PubMed  CAS  Google Scholar 

  72. Shi B, Yaremko B, Hajian G, Terracina G, Bishop WR, Liu M, et al. The farnesyl protein transferase inhibitor SCH66336 synergizes with taxanes in vitro and enhances their antitumor activity in vivo. Cancer Chemother Pharmacol 2000; 46: 387–393.

    Article  PubMed  CAS  Google Scholar 

  73. Yeung SC, Xu G, Pan J, Christgen M, Bamiagis A. Manumycin enhances the cytotoxic effect of paclitaxel on anaplastic thyroid carcinoma cells. Cancer Res 2000; 60: 650–656.

    PubMed  CAS  Google Scholar 

  74. MacKeigan JP, Collins TS, Ting JP. MEK inhibition enhances paclitaxel-induced tumor apoptosis. J Biol Chem 2000; 275: 38953–38956.

    Article  PubMed  CAS  Google Scholar 

  75. Koo HM, Gray-Goodrich M, Kohlhagen G, McWilliams MJ, Jeffers M, Vaigro-Wolff A, et al. The ras oncogene-mediated sensitization of human cells to topoisomerase II inhibitor-induced apoptosis. J Natl Cancer Inst 1999; 91: 236–244.

    Article  PubMed  CAS  Google Scholar 

  76. Brown JM. Therapeutic targets in radiotherapy. Int J Radiat Oncol Biol Phys 2001; 49: 319–326.

    Article  PubMed  CAS  Google Scholar 

  77. Cohen-Jonathan E, Muschel RJ, McKenna WG, Evans SM, Cerniglia G, Mick R, et al. Farnesyltransferase inhibitors potentiate the antitumor effect of radiation on a human tumor xenograft expressing activated HRAS. Radiat Res 2000; 154: 125–132.

    Article  PubMed  CAS  Google Scholar 

  78. Bernhard EJ, Kao G, Cox AD, Sebti SM, Hamilton AD, Muschel RJ, et al. The farnesyltransferase inhibitor FTI-277 radiosensitizes H-ras-transformed rat embryo fibroblasts. Cancer Res 1996: 56: 1727–1730.

    PubMed  CAS  Google Scholar 

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Cox, A.D. (2003). Farnesyltransferase Inhibitors as Anticancer Agents. In: Rak, J. (eds) Oncogene-Directed Therapies. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-313-2_17

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