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Prospective strategies to enforce selectively cell death in cancer cells

Oncogene volume 23, pages 2967–2975 (2004)Cite this article

Abstract

Although induction of apoptosis (cell death mediated by caspases) determines response to cancer therapy, this approach is limited by lack of selectivity in available apoptosis-inducing agents. Furthermore, most cancers, almost by definition, are resistant to apoptosis, growth arrest and cell senescence. Then, how can anticancer agents kill cancer cell without unacceptable toxicity to a patient? The potential therapeutic approaches range from selective inhibition of antiapoptotic pathways, antiangiogenic therapy, tissue-selective therapy (including immunotherapy) to exploitation of, for example, drug resistance, oncoprotein addiction, unrestricted cell cycles, hypermitogenic and hypoxic features of cancer cells. These overlapping and complementary approaches rely on rational drug combinations (at mechanism-based doses and sequences) aimed at matching targets. To ensure killing of cancer cells selectively, we may combine apoptosis- and senescence-inducing agents with inhibitors of apoptosis (to protect normal cells), inhibitors of signal transduction with cell cycle-dependent chemotherapy, antiangiogenic agents with hypoxia-inducible factor-1 inhibitors, tissue-selective therapy with differentiating agents and activators of death receptors with chemotherapy. In theory, consecutive use of these drug combinations may control cancer.

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References

  • Abal M, Andreu JM and Barasoain I . (2003). Curr. Cancer Drug Targets, 3, 193–203.

  • Akay C and Gazitt Y . (2003). Cell Cycle, 2, 358–368.

  • Amarante-Mendes GP, McGahon AJ, Nishioka WK, Afar DE, Witte ON and Green DR . (1998). Oncogene, 16, 1383–1390.

  • An WG, Hwang SG, Trepel JB and Blagosklonny MV . (2000). Leukemia, 14, 1276–1283.

  • An WG, Schnur RC, Neckers L and Blagosklonny MV . (1997). Cancer Chemother. Pharmacol., 40, 60–64.

  • Beg AA and Baltimore D . (1996). Science, 274, 782–784.

  • Berg G, Lindstedt G, Suurkula M and Jansson S . (2002). J. Endocrinol. Invest., 25, 44–52.

  • Bishop PC, Myers T, Robey R, Fry DW, Liu ET, Blagosklonny MV and Bates SE . (2002). Oncogene, 21, 119–127.

  • Blagosklonny MV . (1998). Int. J. Cancer, 78, 511–517.

  • Blagosklonny MV . (2001). Int. J. Oncol., 19, 257–262.

  • Blagosklonny MV . (2002). Nat. Rev. Cancer, 2, 221–225.

  • Blagosklonny MV . (2003a). EMBO Rep., 4, 358–362.

  • Blagosklonny MV . (2003b). Trends Mol. Med., 9, 307–312.

  • Blagosklonny MV . (2003c). Br. J. Cancer, 89, 1147–1151.

  • Blagosklonny MV . (2003d). Drug Discov. Today, 8, 1104–1107.

  • Blagosklonny MV and Darzynkiewicz Z . (2002). Cell Cycle, 1, 375–382.

  • Blagosklonny MV, Fojo T, Bhalla KN, Kim JS, Trepel JB, Figg WD, Rivera Y and Neckers LM . (2001). Leukemia, 15, 1537–1543.

  • Blagosklonny MV, Robey R, Sheikh MS and Fojo T . (2002). Cancer Biol. Ther., 1, 113–117.

  • Blalock WL, Navolanic PM, Steelman LS, Shelton JG, Moye PW, Lee JT, Franklin RA, Mirza A, McMahon M, White MK and McCubrey JA . (2003). Leukemia, 17, 1058–1067.

  • Brenner C, Le Bras M and Kroemer G . (2003). J. Clin. Immunol., 23, 73–80.

  • Broker LE, Huisman C, Ferreira CG, Rodriguez JA, Kruyt FAE and Giaccone G . (2002). Cancer Res., 62, 4081–4088.

  • Brown JM and Giaccia AJ . (1998). Cancer Res., 58, 1408–1416.

  • Chang F, Lee JT, Navolanic PM, Steelman LS, Shelton JG, Blalock WL, Franklin RA and McCubrey JA . (2003). Leukemia, 17, 590–603.

  • Cohn DE and Herzog TJ . (2000). Curr. Opin. Oncol., 12, 492–496.

  • Daley GQ . (2003). Cell Cycle, 2, 190–191.

  • Dancey J and Sausville EA . (2003). Nat. Rev. Drug Discov., 2, 296–313.

  • Dancey JE and Freidlin B . (2003). Lancet, 362, 62–64.

  • Debatin KM, Poncet D and Kroemer G . (2002). Oncogene, 21, 8786–8803.

  • Dixon H and Norbury CJ . (2002). Cell Cycle, 1, 362–368.

  • Druker BJ . (2002). Cancer Cell, 1, 31–36.

  • Ebnoether M, Stentoft J, Ford J, Buhl L and Gratwohl A . (2002). Lancet, 359, 1751–1752.

  • Folkman J . (1971). N. Engl. J. Med., 285, 1182–1186.

  • Frei E . (1985). Cancer Res., 45, 6523–6537.

  • Fulda S, Meyer E, Friesen C, Susin SA, Kroemer G and Debatin KM . (2001). Oncogene, 20, 1063–1075.

  • Fulda S, Wick W, Weller M and Debatin KM . (2002). Nat. Med., 8, 808–815.

  • Fumo G, Akin C, Metcalfe DD and Neckers L . (2003). Blood.

  • Garrido C, Schmitt E, Cande C, Vahsen N, Parcellier A and Kroemer G . (2003). Cell Cycle, 2, 579–584.

  • George D . (2003). Adv. Exp. Med. Biol., 532, 141–151.

  • Giaccia A, Siim BG and Johnson RS . (2003). Nat. Rev. Drug Discov., 2, 803–811.

  • Giannakakou P, Robey R, Fojo T and Blagosklonny MV . (2001). Oncogene, 20, 3806–3813.

  • Goncalves A, Braguer D, Carles G, Andre N, Prevot C and Briand C . (2000). Biochem. Pharmacol., 60, 1579–1584.

  • Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ and Giaccia AJ . (1996). Nature, 379, 88–91.

  • Grant S and Dent P . (2002). Cell Cycle, 1, 383–388.

  • Harris AL . (2002). Nat. Rev. Cancer, 2, 38–47.

  • Houghton JA . (1999). Curr. Opin. Oncol., 11, 475–481.

  • Ibrado AM, Liu L and Bhalla K . (1997). Cancer Res., 57, 1109–1115.

  • Jia W, Yu C, Rahmani M, Krystal G, Sausville EA, Dent P and Grant S . (2003). Blood, 102, 1824–1832.

  • Jin Z, Dicker DT and El-Deiry WS . (2002). Cell Cycle, 1, 82–89.

  • Johnstone RW, Ruefli AA and Lowe SW . (2002). Cell, 108, 153–164.

  • Jones RH and Vasey PA . (2003). Eur. J. Cancer, 39, 147–156.

  • Kerbel R and Folkman J . (2002). Nat. Rev. Cancer, 2, 727–739.

  • Kerbel RS . (1997). Nature, 390, 335–336.

  • Kim CY, Tsai MH, Osmanian C, Graeber TG, Lee JE, Giffard RG, DiPaolo JA, Peehl DM and Giaccia AJ . (1997). Cancer Res., 57, 4200–4204.

  • Klement G, Huang P, Mayer B, Green SK, Man S, Bohlen P, Hicklin D and Kerbel RS . (2002). Clin. Cancer Res., 8, 221–232.

  • Krishnamachary B, Berg-Dixon S, Kelly B, Agani F, Feldser D, Ferreira G, Iyer N, LaRusch J, Pak B, Taghavi P and Semenza GL . (2003). Cancer Res., 63, 1138–1143.

  • Leverkus M, Sprick MR, Wachter T, Mengling T, Baumann B, Serfling E, Brocker EB, Goebeler M, Neumann M and Walczak H . (2003). Mol. Cell. Biol., 23, 777–790.

  • Levis M, Allebach J, Tse KF, Zheng R, Baldwin BR, Smith BD, Jones-Bolin S, Ruggeri B, Dionne C and Small D . (2002). Blood, 99, 3885–3891.

  • Mack PC, Gandara DR, Lau AH, Lara Jr PN, Edelman MJ and Gumerlock PH . (2003). Cancer Chemother. Pharmacol., 51, 337–348.

  • MacKeigan JP, Collins TS and Ting JP-Y . (2000). J. Biol. Chem., 275, 38953–38956.

  • Martin SJ and Green DR . (1994). Curr. Opin. Oncol., 6, 616–621.

  • Mayer F, Stoop H, Scheffer GL, Scheper R, Oosterhuis JW, Looijenga LH and Bokemeyer C . (2003). Clin. Cancer Res., 2, 767–773.

  • McCarty MF . (2003). Med. Hypotheses, 61, 509–511.

  • Merlin JL, Bour-Dill C, Marchal S, Bastien L and Gramain MP . (2000). Anti-cancer Drugs, 11, 295–302.

  • Milner AE, Palmer DH, Hodgkin EA, Eliopoulos AG, Knox PG, Poole CJ, Kerr DJ and Young LS . (2002). Cell Death Differ., 9, 287–300.

  • Mitsiades N, Mitsiades CS, Richardson PG, Poulaki V, Tai YT, Chauhan D, Fanourakis G, Gu X, Bailey C, Joseph M, Libermann TA, Schlossman R, Munshi NC, Hideshima T and Anderson KC . (2003). Blood, 101, 2377–2380.

  • Monks A, Harris ED, Vaigro-Wolff A, Hose CD, Connelly JW and Sausville EA . (2000). Invest. New Drugs, 18, 95–107.

  • Motwani M, Delohery TM and Schwartz GK . (1999). Clin. Cancer Res., 5, 1876–1883.

  • Mueller T, Voigt W, Simon H, Fruehauf A, Bulankin A, Grothey A and Schmoll HJ . (2003). Cancer Res., 63, 513–521.

  • Orlowski RZ and Baldwin ASJ . (2002). Trends Mol. Med., 8, 385–389.

  • Overwijk WW and Restifo NP . (2000). Crit. Rev. Immunol., 20, 433–450.

  • Panvichian R, Orth K, Day ML, Day KC, Pilat MJ and Pienta KJ . (1998). Cancer Res., 58, 4667–4672.

  • Pardee A . (2002). Cancer Biol. Ther., 1, 426–427.

  • Pepper C, Thomas A, Hoy T, Tighe J, Culligan D, Fegan C and Bentley P . (2003). Cell Cycle, 2, 53–58.

  • Pelikan DM, Lion HL, Hermans J and Goslings BM . (1997). Clin. Endocrinol. (Oxf), 47, 713–720.

  • Perkins CL, Fang G, Kim CN and Bhalla KN . (2000). Cancer Res., 60, 1645–1653.

  • Prokop A, Wieder T, Sturm I, Essmann E, Seeger K, Wuchter C, Ludwig WD, Henze G, Dorken B and Daniel PT . (2000). Leukemia, 14, 1606–1613.

  • Reed JC . (2003). Cancer Cell, 3, 17–22.

  • Reese DM . (2000). Lancet, 355, 1474–1475.

  • Roninson IB . (2003). Cancer Res., 63, 2705–2715.

  • Sane AT and Bertrand R . (1999). Cancer Res., 59, 3565–3569.

  • Sattlermc M and Griffin JD . (2003). Semin. Hematol., 40 (Suppl 3), 4–10, 40, S4–S10.

  • Sawyers CL . (2002). Cancer Cell, 1, 413–415.

  • Sayers TJ, Brooks AD, Koh CY, Ma W, Seki N, Raziuddin A, Blazar BR, Zhang X, Elliott PJ and Murphy WJ . (2003). Blood, 102, 303–310.

  • Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM and Lowe SW . (2002). Cell, 109, 335–346.

  • Shao RG, Cao CX, Shimizu T, O'Connor PM, Kohn KW and Pommier Y . (1997). Cancer Res., 57, 4029–4035.

  • Skorski T . (2002). Oncogene, 21, 8591–8604.

  • Sellers WR and Fisher DE . (1999). J. Clin. Invest., 104, 1655–1661.

  • Semenza GL . (2002). Trends Mol. Med., 8, S62–S67.

  • Semenza GL . (2003). Nat. Rev. Cancer, 3, 721–732.

  • Shah MA and Schwartz G . (2001). Clin. Cancer Res., 7, 2168–2181.

  • Simon D, Korber C, Krausch M, Segering J, Groth P, Gorges R, Grunwald F, Muller-Gartner HW, Schmutzler C, Kohrle J, Roher HD and Reiners C . (2002). Eur. J. Nucl. Med. Mol. Imaging, 29, 775–782.

  • Sohal J, Phan VT, Chan PV, Davis EM, Patel B, Kelly LM, Abrams TJ, O'Farrell AM, Gilliland DG, Le Beau MM and Kogan SC . (2003). Blood, 101, 3188–3197.

  • Solary E, Droin N, Bettaieb A, Corcos L, Dimanche-Boitrel MT and Garrido C . (2000). Leukemia, 14, 1833–1849.

  • Solit DB, Basso AD, Olshen AB, Scher HI and Rosen N . (2003). Cancer Res., 63, 2139–2144.

  • Spierings DC, de Vries EG, Vellenga E and de Jong S . (2003). Cell Death Differ., 10, 808–822.

  • Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ and Krek W . (2003). Nature, 425, 307–311.

  • Strair RK, Schaar D, Goodell L, Aisner J, Chin KV, Eid J, Senzon R, Cui XX, Han ZT, Knox B, Rabson AB, Chang R and Conney A . (2002). Clin. Cancer Res., 8, 2512–2518.

  • Szlosarek PW and Balkwill FR . (2003). Lancet Oncol., 4, 565–573.

  • Voelkel-Johnson C . (2003). Cancer Biol. Ther., 2, 283–290.

  • von Mehren M . (2003). Cancer Invest., 21, 553–563.

  • Wang CY, Mayo MW, Korneluk RG, Goeddel DV and Baldwin ASJ . (1998). Science, 281, 1680–1683.

  • Wang JL, Wang X, Wang H, Iliakis G and Wang Y . (2002). Cell Cycle, 1, 267–272.

  • Wilkinson E . (2002). Lancet Oncol., 3, 583.

  • Winegarden JD, Mauer AM, Gajewski TF, Hoffman PC, Krauss S, Rudin CM and Vokes EE . (2003). Lung Cancer, 39, 191–196.

  • Yao Q, Nishiuchi R, Li Q, Kumar AR, Hudson WA and Kersey JH . (2003). Clin. Cancer Res., 9, 4483–4493.

  • Yu C, Wang S, Dent P and Grant S . (2001). Mol. Pharmacol., 60, 143–154.

  • Yu JL, Rak JW, Coomber BL, Hicklin DJ and Kerbel RS . (2002). Science, 295, 1526–1528.

  • Zhivotovsky B and Orrenius S . (2003). Semin. Cancer Biol., 13, 125–134.

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  1. Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Ave., Hawthorne, Vlahalla, 10532, NY, USA

    Mikhail V Blagosklonny

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Blagosklonny, M. Prospective strategies to enforce selectively cell death in cancer cells. Oncogene 23, 2967–2975 (2004). https://doi.org/10.1038/sj.onc.1207520

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