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Specific cell-signal targets for cancer chemotherapy

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Abstract

Attempts to develop drugs, specific for cancer cells, are dealt here according to the intended cell-target. While many target specific drugs were developed, they reach only moderate successes in clinics for reasons, such as, delivery problem, lack of in vivo efficacy or toxicity. However, recent efforts focusing on the diversity of tyrosine kinases, participating in cell-signal transduction, brought fruit. The firs such drug, Givec, approved by the USFDA recently, is used in clinics with great success to threat CML The drug inhibits tyrosin kinase of bcr-abl, c-abl and v-abl. Work is progressing on other tyrosin kinase inhibitors and on other type of specific cancer cell signal protein inhibitors. These efforts are hoped to yield better cures for cancer in the near future.

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References

  • Actis, A. M., Caruso, S. P., and Levin, E., Opposite effect of a cAMP analogue on tumor growth related to hormone dependence of a murine mammary tumor. Cancer Lett., 96 81–85 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Antoniades, H. N., Galanopoulos, T., Neville-Golden, J., and OHara CJ., Malignant epithelal cells in primary human lung carcinomas coexpressed in vivo platlet-derived growth factor (PDGF) and PDGF receptor mRNA and their protein products. Proc. Natl. Acad. Sci., 89, 3942–3946 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Asiedu, C., Biggs, J., Lilly, M., and Kraft, A. S., Inhibition of leukemic cell growth by the protein kinase C activator bryostatin 1 corre-lates with the dephosphorylation of cyclin-dependent kinase 2. Cancer Res., 55, 3716–3720 (1995).

    PubMed  CAS  Google Scholar 

  • Bacus, S. S., Stancovski, I., Huberman, E., Chin, D., Hurwitz, E., Mills, G. B., Ullrich, A., Sela, M., and Yarden, Y., Tumorinhibitory monoclonal antibodies to the HER-2/Neu receptor induce differentiation of human breast cancer cells. Cancer Res., 52, 2580–2589 (1992).

    PubMed  CAS  Google Scholar 

  • Beran, M., Caox, X., Csitrov, Z., Jeha, S., Jin, G., OBrien, S., Talpaz, M., Arlinghause, R. B., Lydon, N. B., and Kartarjian, H., Selective inhibition of cell proliferation and BCR-ABL phosphorylation in acute lymphoblastic leukemia cells expressing M: 190,00 BCR-ABL proteins by a tyrosine kinase inhibitor (CGP 57148). Clinical Cancer Res., 4, 1661–1672 (1998).

    CAS  Google Scholar 

  • Bishop, J. M., The molecular genetics of cancer. Science, 235, 305–311 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Bishop, W. R., Patton, R., Bohanon, S., Bergman, G., Meyers, M., Braun, C., Khuri, F., and Kirschmeier, P., Evaluation of bio-chemical markers of protein farnesylation in human tumor speci-mens following treatment with oral SCH66336, an inhibitor of famesyl protein transferases. Proc. Am. Assoc. Cancer Res., 42, 259 (2001).

    Google Scholar 

  • Blau, C. A., Constantoulakis, P., Shaw, C. M., and Stamatoyannopoulos, G., Fetal hemoglobin induction with butyric acid: efficacy and toxicity. Blood, 81, 529–37 (1993).

    PubMed  CAS  Google Scholar 

  • Bleckburn, E. H., Telomerases. Ann. Rev. Biochem., 61, 113–129 (1992).

    Article  Google Scholar 

  • Boe, R., Grejtsen, B. T., Doskeland, S. O., and Vintermyr, O. K., 8-CI-cAMP induces apoptotic cell death in a mam-mary carcinoma cell (MCF-7) line. Br. J. Cancer, 72, 1151–1159 (1995).

    PubMed  CAS  Google Scholar 

  • Buser, C. A., Anthony, N., Bell, I. Dinsmore, C., Gibba, J., Graham, S., Hartman, S., Kohl, N., Lobbel, R., Lumma, B., Williams, T., and Huber, H., LC/MS Characterization of Ki-Ras prenylation after treatment with selective and dual inhibitors of FPTase and GGPT ase-l in pre-clinical mouse model. Proc. Am. Assoc. Cancer Res., 42, 486 (2001).

    Google Scholar 

  • Budillon, A., Guarrasi, R., Gennaro, E. D., Bruzzese, F., Errico, S., Pirozzi, G., Caraglia, M., Avallone, A., Tassonel, P. F., Lombardi, M. L., Caponigro, F., Venuta., and Tagia-ferri, P., ZD1839 (“Iressa”), an EGFR tyrosine kinase inhi-bitor, potentiates non-Mhc restricted cytotoxicity in human cancer cell lines. Proc. Am. Assoc. Cancer Res., 42, 802 (2001).

    Google Scholar 

  • Buguet-Fagot, C., Lallemand, F., Charollais, R.H., and Mester, J., Sodium butyrate inhibits the phosphorylation of the retinobla-stoma gene product in mouse fibroblasts by a transcription dependent mechanism. J. Cell. Physiol., 166, 631–636 (1966).

    Article  Google Scholar 

  • Carducci, M., Bowling, M., Eisenberger, M., Sinibaldi, V., Simons, S., Chen, T., Noc, D., Graham, L., and Done-hover, R., Phenyl-butyrate (PB) for refractory solid tumors: A phase I clinical and pharmacological evaluation. Proc. Am. Assoc. Cancer Res., 37, 371–376 (1996).

    Google Scholar 

  • Caroll, M., Ohno-Jones, S., Tamura, S., Buchdunger, E., Zimmermann, J., Lydon, N. B., and Gilliland, D. G., CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL and TEL-PDGFR fusion proteins. Blood, 90, 4947–4952 (1997).

    Google Scholar 

  • Ciardiello, F., Caputo, R., Bianco, R., Damiano, V., Pomatico, G., De Placido, S., Bianco, A. R., and Tortora, G., Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selec-tive tyrosine kinase inhibitor. Clin. Cancer Res., 6, 2053–2059 (2000).

    PubMed  CAS  Google Scholar 

  • Cobb, M. H., and Goldsmith, E. J., How MAP kinases are regulated. J. Biol. Chem. 270, 14843–14846 (1995).

    Article  PubMed  CAS  Google Scholar 

  • De Luca, L. M., Retinoids and their receptors in differentiation, embriogenesis and neoplasia. FASEB J., 5, 2924–2933 (1991).

    PubMed  Google Scholar 

  • Deninger, M. W., Goldman, J. M. V., Lydon, N., and Melo, J. V., The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood, 90, 3691–3698 (1997).

    Google Scholar 

  • Derexler, H. G., Gignak, S. M., Jones, R. A., Scott, C. S., Pettit, G. R., and Hoffbrand, A. V., Bryostatin 1 induces differentiation of B-chronic lymphocytic leukemia cells. Blood, 74, 1747–1757 (1989).

    Google Scholar 

  • de The, H., Vivanco-Ruiz, M., Tiollais, P., Stunnenberg, H., and Dejean, A., Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature, 343, 177–180 (1990).

    Article  PubMed  Google Scholar 

  • Druker, B. J., Tamura, S., Buchdunger, E., Ohno, T., Segal, G. M., Fannings, S., Zimmermann, J., and Lydon, N. B., Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nature Medicine, 2, 561–568 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Ezzat, S., Kontogeorgos, G., Redelmeier, D. A., Horvath, E., Harvis, A. G., and Kovacs K., In vivo responsiveness of morpho-logical variants of growth hormone-producing pituitary adenoma to octreotide. Eur. J. Endoctrinol., 133, 686–690 (1995).

    Article  CAS  Google Scholar 

  • Fletcher, T. M. and Chen, S. F., The effect of 7-deaza-2-deoxyguanosine-5-triphosphate and 7-deaza-2deoxyadenosine-5-tri-phosphate on telomerase activity. Ann. Oncol., 7 (suppl 1), 71 (1996).

    Google Scholar 

  • Franke, T. F., Kaplan, D. R., Cantley, LC., and Toker, A., Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-biphosphate. Science, 275, 665–668 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Fritz, J., Waechter, M., Zang, C., von Deimling, A., Possinger, K., Reichart, J., Koeffler, P., and Elstner, E., Combination of pioglita-zone (PGZ) and all-trans-retinoic acid (ATRA) inhibits clonal growth and induces apoptosis of cancer cells. Proc. Am. Assoc. Cancer Res., 42, 445 (2001).

    Google Scholar 

  • Fujioka, T., Ishikura, K., Hasegawa, M., Ogyu, K., Matsushita, Y., Sato, M., Sato, F., Aoki, H., and Kubo, T., Antimumor effect of oral administration of an interferon-inducing pyrimidinone, bropirimine, on murine renal-cell carcinoma. Cancer Chemother. Pharmacol., 36, 7–12 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., and Weinberg, R. A., Creation of human tumor cells with defined genetic elements. Nature, 400, 464–468 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Han, Z., Chatterjee, D., Early, J., Pantazis, P., Hendrickson, E. A., and Wyche, J.H., Isolation and characterization of an apoptosis resistant variant of human leukemia HL-60 cells that has switched expression from Bcl-2 to Bcl-xI. Cancer Res. 56, 1621–2628 (1996).

    PubMed  CAS  Google Scholar 

  • Harley, C. B., Kim, N. W., Prowse, K., Weinrich, S. L., Hirsch, K. S., West, M. D., Bacchetti, S., Hirte, H. W., Counter, C. M., and C. W., Telomerase, cell immortality and cancer. Cold Sping Harbor Symp. Quant. Biol., 59, 307–315 (1994).

    CAS  Google Scholar 

  • Hiyama, E., Hiyama, R., Yokoiama, T., Matsuura, Y., Piatszek, M. A., and Shay, J. W., Correlating telo-merase activity levels with human neuroblastoma out-comes. Nature Med., 1, 249–255 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Hiyama, E., Yokoyama, T., Tatsumoto, N., Hiyamaka, K., Imamura, Y., Murakami, Y., Kadama, T., Piatszek, M. A., Shay, K., and Matsuura, Y., Telomerase activity in gastric cancer. Cancer Res., 55, 3258–3262 (1995).

    PubMed  CAS  Google Scholar 

  • Hohl, R. J., Lewis-Tisebar, K., Pogatchik, D. M., and Wiemer, D. F., Structural requirement for inhibition of farnesyl protein trans-ferase by isoprenoid phosphonic acid. Proc. Am. Assoc. Cancer Res. 37, 426 (1996).

    Google Scholar 

  • Ibrahim, S., Peggins, J., Knapton, A., Licht, T., and Aszalos, A., Influence of antipsychotic, antiemetic, and Ca2+ channel blocker drugs on the cellular accumulation of the anticancer drug daunorubicine: P-glycoprotein modulation, J. Pharmaco. Exper, Therapeutics 295, 1276–183 (2000).

    CAS  Google Scholar 

  • Kaur, G., Stetler-Stevenson, M., Sebers, S., Worland, P., Sedlacek, H., Myers, C., Czech, J., Naik, R., and Sausville, E., Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275. J. Natl. Cancer Inst., 84, 1736–1740 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Kim, E., Glisson, B. S., Meyers, M. L., Herbert, R. S., Shin, D. M., Statkevich, P., Bangert, S., Hong, W. K., and Khuri, F.R., A phase I/II study of the farnesyl transferase inhibitor (FTI) SCH66336 with paclitaxel in patients with solid tumors. Proc. Am. Assoc. Cancer Res., 42, 488 (2001).

    Google Scholar 

  • Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L., Coviello, G. M., Wright, W.E., Weinrich, S. L., and Shay, J. W., Specific association of human telomerase activity with immortal cells and cancer. Science, 266, 2011–2015 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Kraemer, K. H., DiGiovanna, J. J., Moshell, A. N., Tarone, R. E., and Peck, G. L., Prevention of skin cancer in xerodema pigmentosum with the use of oral isoretinoin. N. Engl. J. Med., 318, 1633–1637 (1988).

    PubMed  CAS  Google Scholar 

  • Krupitza, G., Grill, S., Harant, H., Hulla, W., Szekeres, T., Huber, H., and Dittrich, C., Genes related to growth and invasivness are repressed by sodium butyrate in ovarian carcinom cells. Br. J. Cancer, 73, 433–438 (1966).

    Google Scholar 

  • Lamberts, S. W. J., Koper, J. W., and Reubi, J. C., Potential role of somatostatin analogues in the treatment of cancer. J. Clin. Invest., 17, 281–287 (1987).

    Article  CAS  Google Scholar 

  • IeCountre, P., Mologni, L., Cleris, L., Marschesi, E., Buchdunger, E., Giardini, R., Formelli, F., and Gambacorti-Passerini, C., In vivo eradication of human BCR/ABL-positive leukemia cells with ABL kinase inhibitor. J. Natl. Cancer Inst., 91, 163–168 (1999).

    Article  Google Scholar 

  • Leftheris, K., Kline, T., Vite., G. D., Cho, Y. M., Bhide, R. S., Patel, D. V., Schmidt, P. J., Weller, H. N., Andahazy, M. L., Carboni, J. M., Gullo-Braun, J. L., Lee, F. Y., Ricca, C., Rose, W. C., Development of highly potent inhibitors of Ras famesyl-transferase possessing cellular and in vivo activity, J. Med. Chem., 39, 224–236 (1996)

    Article  CAS  Google Scholar 

  • Levitzki, A. and Gazit, A., Tyrosine kinase inhibition: An approach to drug development. Science, 267, 1782–1788 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Liebow, C., Reilly, C., Serrano, M., and Schally, A. V., Somatostatin analogs inhibit growth of pancreatic cancer by stimulating tyro-sine phosphatase. Proc. Natl. Acad. Sci., 86, 2003–2007 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Lippman, S. M., Clark, L. C., and Parkinson, D., Pharmacologic prevention and therapy of skin cancer. In: Chemo and immuno prevention of cancer. Pastorino, U. and Hong, W.K.: eds, George Thiem Verlag, Stuttgart, 1991, pp 177–187.

    Google Scholar 

  • Lotzava, E., Savary, C. A., and Stringfellow, D.A., 5-halo-6- phenyl pyrimidinones: new molecules with cancer therapeutic potential and interferon-inducing capacity are strong inducer of murine natural killer cells. J. Immunol., 130, 965–969 (1983).

    Google Scholar 

  • Mahon, F. V., Deninger, M. W. N., Schultheis, B. Chabrol, J., Reiffers, J., Geldman, J. M., and Melo, J. V., Selection and characterizatin of BCR-ABL positive cell lines with different selectivity to tyrosine kinase inhibitor imatinib: divers mechanisms of resistance. Blood, 96, 10701079 (2000).

    Google Scholar 

  • Main, J. P., Chen, S. E., and Windle, B., Interaction between telo-merase oligonucleotide primers and CHO non-processive telo-merase. Proc. Am. Soc. Cancer Res., 36, 561 (1996).

    Google Scholar 

  • Maki, A., Diwakaran, H., Redman, B., Al-Asfors, M., Pettit, G. R., Mohammed, R. M., and Al-Katib, A., The bcl-2 and p53 oncopro-teins can be modulated by bryostatin 1 and dolastatins in human diffuse large cell lymphoma. Anticancer Drugs, 6, 392–397 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Malik, S., Brattain, M., Rowinsky, E., Miller, A., Duffey, D., de Graffenried, L., Siu, L., Simmons, C., Kreisberg, J., Nadler, P., and Hidalgo, M., Inhibition of the epidermal growth factor receptor (EGFR) activation and signaling by OSI-774, a novel EGFR inhibitor, in clinical specimens of head and neck carcinoma. Proc. Am. Assoc. Cancer Res., 42, 852 (2001).

    Google Scholar 

  • Mason, W., Malkin, M., Lieberman, F., Cropp, G., and Hannah, A., Pharmacokinetics of SU101, a novel signal transduction inhi-bitor, in patients with recurrent malignant glioma. Proc. Am. Assoc. Cancer Res., 37, 166–167 (1996).

    Google Scholar 

  • Miller, A. A., Kurschel, E., Osieka, R., and Schmidt, C. G., Clinical pharmacology of sodium butyrate in patients with acute leukemia. Eur. J. Clin. Oncol., 23, 1283–1287 (1987)

    Article  CAS  Google Scholar 

  • Mohammed, R. M., Diwakaran, H., Maki, A., Emara, M. A., Pettit, G. R., Redman, B., and Al-Katib, A., Bryostatin induces apoptosis and augments inhibitory effects of vincristin in human diffuse large cells. Leuk. Res., 19, 667–673 (1995).

    Article  Google Scholar 

  • Moulder, S. L., Yakes, F. M., Bianco, R., and Arteaga, C. L., A rational for the use of small molecule EGF receptor tyrosine kinase inhibitors against HER2/neu (erbB-2) overexpressing breast tumor cells. Proc. Am. Assoc. Cancer Res., 42, 853 (2001).

    Google Scholar 

  • Muindi, J., Frankel, S. R., Miller, W. H., Jakubowski, A., Scheinberg, D. A., Young, C. W., Dimitrovsky, E., and Warress, R. P. Jr., Continuous treatment with all-trans retinoic acid causes a progressive reduction for reduction in plasma drug concentration: Implication for relapse and retinoid resistance in patients with acute promyelocytic leukemia. Blood, 79, 299–303 (1992).

    PubMed  CAS  Google Scholar 

  • Mullin, R. J., Alligood, K. J., Allen, P. P., Crosby, R. F. M., Keith, B. R., Lakckey, K., Gillmer, T. M., Griffin, R. J., Murray, D. M., and Tadepalli, S. M., Antitumor activity of GW2016 in the EGFR positive human head and neck cancer xenograft, HN5. Proc. Am. Assoc. Cancer Res., 42, 854 (2001).

    Google Scholar 

  • Napoli, J. L., The biogenesis of retinoic acid: a physiologically significant promoter of differentiation. In: Chemistry and biology of retinoic acid. Dawson, M.I. and Okamura, H.: eds, CRC Press, Boca Raton, Fl, 1990, pp 229–249.

    Google Scholar 

  • North, P. S., Davies, S. L., Ciardiello, F., Damiano, V., Bianco, C., Pepe, S., Bianco, A. R., Harris, A. L., Hickson, I. D., and Tortora, G., Overexpression of the Rl alpha subunit of protein kinase A confers hypersensitivity to topoisomerase II inhibitors and 8-CI-cyclic adenosine 3,5- monophosphate in Chinese hamster ovary cells. Cancer Res., 54, 4123–4128 (1994).

    PubMed  CAS  Google Scholar 

  • Novogrodsky, A., Dvir, A., Ravid, A., Shkolnik, T., Stemel, K. H., Rubin, A. L., and Zaizov, R., Effect of polar organic compounds on myeloid cells: butyrate induced partial remission of acute myelogenous leukemia in a child. Cancer, 51, 9–14 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Nudelman, A., Ruse, A., Aviram, A., Rabizadeh, E., Shaklai, M., Zimrah, Y., and Raphaeli, A., Novel anticancer prodrug of butyric acid. J. Med. Chem. 35, 687–694 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Patnaic, A., Izbicka, E., Eckhardt, S. G., Davidson, K., Goetz, A., McCreeny, H., Tolcher, A., Mori, M., Terada, K., Bal, K., Rybak, A., Thibault, H., Richards, L., Gentler, L., and Rowinsky, E., Inhibition of HDJ2 protein farnesylation in peripheral blood mononuclear cells as a pharmacodynamic endpoint in a phase I study of R115777 and gemcitabine. Proc. Am. Assoc. Cancer Res., 42, 488 (2001).

    Google Scholar 

  • Perkins, A. S. and Stern, D. F., Molecular Biology of Cancer: Oncogens. In Cancer: Principle and Practice of Oncology, De Vita, V. T., Hellman, S. and Rosenberg, S. A.: eds. Lippincott, Philadelphia, 1997, pp 79–102.

    Google Scholar 

  • Pettit, G. R., The bryostatins. In progress in the chemistry of organic natural products. Herz, W., Kirby, G.W., Steglich, W. and Tamm, C.H.: eds, Spinger, Vienna, 1991, pp 153–195.

    Google Scholar 

  • Philip, P. A., Rea, D., Thavasu, P., Crmichael, J., Stuart, N.S., Rokett, H., Talbot, D.C., Ganesau, T., Pettit, G. R., and Balkwill, F., Phase I study of bryostatin 1: Assessment of interlukin 6 and tumor necrosis factor alpha induction in vivo. J. Natl. Cancer Inst., 85, 1812–1818 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Ramage, A. D., Langdon, S. P., Ritchie, A. A., Burns, D. J., and Miller, W. R., Growth inhibition by 8-Cloro-cyclic AMP of human HT29 colorectal and ZR-75-1 breast carcinoma xenografts is associated with selective modulation of protein kinase A isoenzymes. Europ. J. Cancer, 31A, 969–973 (1995).

    Article  CAS  Google Scholar 

  • Rambaldi, A., Biondi, A., Pandolfi, P. P., Torcia, M., Bettoni, S., Vannier, E., Barbui, T., Shaw, A. B., Dinerello, C. A., and Cozzolino, F., Modulation of cell proliferation and cytokine production in acute myeloblastic leukemia by interlukin-1 receptor antagonist and lack of its expression. Blood, 78, 3248–3253 (1991).

    PubMed  CAS  Google Scholar 

  • Raphaeli, A., Rabizadeh, E., Aviram, A., Shaklai, M., Ruse, M., and Nudelman, A., Derivatives of butyric acid as potential antineo-plastic agents. Int. J. Cancer, 49, 66–72 (1991).

    Article  Google Scholar 

  • Riou, J. F., Mailliet, P., Laoui, A., Renou, E., Petitgenet, O., Guittat, L., and Mergny, J., Apoptosis, cell senescence and telomerase shortening induced by a new series of specific G- quadruplex DNA ligand. Proc. Am. Assoc. Cancer Res., 42, 837 (2001)

    Google Scholar 

  • Rosato, R. R., Almenara, J. A., Cartee, L. A., and Grant, S., The cydine-dependent kinase inhibitor flavopiridol disrupts sodium butyrate-induced p21waf-1CIP1 expression and enhances apopto-sis in human myeloid leukemia cells. Proc. Am. Assoc. Cancer Res., 42, 437 (2001).

    Google Scholar 

  • Santini, V., Lamberts, S. W., Krenning, E. P., Bachx, B., and Lowenberg, E., Somatostatin and its cyclic octapeptide analo-gue SMS 201-995 as inhibitor of proliferation of human acute lymphoblastic and acute myeloid leukemia. Leuk. Res., 19, 707–712 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Sarosdy, M. F., Lamm, D. L., Williams, R. D., Moon, T. D., Flanigen, R. C., Crawford, E. D., Wilks, N. E., Earhart, R. H., and Merritt, J. A., Phase I trial of oral bropirimine in superficial bladder cancer. J. Urology, 147, 31–33 (1992).

    CAS  Google Scholar 

  • Sawyers, C., Hochhaus, A., Feldman, E., Goldman, J. M., Miller, C., Ben-Am, M., Capdenlle, R., and Dumber, B., A phase II study to determine the safety and anileukemic effects of ST1571 in patients with Philadelphia chromosome positive chronic myeloid leukemia in myeloid blast crisis. Blood, 96, 503a (2000).

    Google Scholar 

  • Sebold-Leopold, J. S., Govan, R. C., Gibbs, B. S., Przybranowski, S., Latash, M., Leopold, W. R., Scholten, J., Zimmerman, K., Hupe, D., Leonard, D., McNamara, D., Bur, S., Bolton, G. L., and Doherty, A. M., Biological evaluation of cell permeable inhibitors of ras famesyl trasferase. Proc. Am. Assoc. Cancer Res., 37, 423 (1996).

    Google Scholar 

  • Shapiro, G. I. and Harper, J. W., Anticancer drug targets: cell cycle and checkpoint control J. Clin. Invest., 104, 1645–1653 (1999).

    Article  CAS  Google Scholar 

  • Smith, V., Brunton, L., Valenti, M., Johnson, S., Workman, P., and Kelland, L., Preclinical antitumor and pharmacodynamic studies with the famesyl transferase inhibitor (FTI) R115777. Proc. Am. Assoc. Cancer Res., 42, 260 (2001).

    Google Scholar 

  • Steube, K. G. and Dexler, H. G., The protein kinase activator bryostatin 1 induces the rapid release of TNF alpha from MONO-MAC-6 cells. Biochem. Biophys. Res. Commun., 214, 1197–1203 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Stringfellow, D. A., Vanderberg, H. C., and Weed, S.D., Interferon induction by 5-halo-6-phenyl pyrimidinones. J. Interferon Res., 1, 1–14 (1980).

    PubMed  CAS  Google Scholar 

  • Sun, J., Ohkanda, J., Adnane, J., Lockman, J., Hamilton, A., and Sebti, S. M., Geranylgeranyltransferase I (GGTase I) inhibitors induce mammary tumor regression in oncogenic H- ras transgenic mice: validation of GGTase I as a cancer therapy target. Proc. Am. Assoc. Cancer Res., 42, 260 (2001).

    Google Scholar 

  • Sun, J., Pei, Z., and Sebti, S. M., Stable expression of a 5’400 bp antisense of the beta subunit of farnesyltransferase in human lung carcinoma blocks oncogenic signaling in vitro and in vivo. Proc. Am. Assoc. Cancer Res., 37, 419 (1996).

    Google Scholar 

  • Sun, J., Quian, Y., Hamilton, A. D., and Sebti, S. M., Ras CAAX peptidomimetic FTI-276 selectively blocks tumor growth in nude mice of a human lung carcinoma with K-ras mutation and p53 deletion. Cancer Res., 55, 4243–4247 (1995).

    PubMed  CAS  Google Scholar 

  • Tong, K. P., De Weese, T. L., Mansfield, E. P., and Carducci, M.A., New Insights into phenylbutyrate bioactivity in human prostate cancer. Proc. Am. Assoc. Cancer Res., 37, 361 (1996).

    Google Scholar 

  • Vintermyr, O. K., Boe, R., Brustung, O. T., Maronde, E., Aakvaag, A., and Doskeland, S. O., Cyclic adenosine monophosphate (cAMP) analog 8-CI- and 8-NHZ-cAMP induce cell death independently of cAMP kinase-mediated inhibition of the G1/S transition in mammary carcinoma cells (MCF-7). Endocrinology, 136, 1523–2520 (1995).

    Article  Google Scholar 

  • Wierenga, W., Antiviral and other bioactivities of pyrimidinones. Pharm. Ther., 30, 67–89 (1985).

    Article  CAS  Google Scholar 

  • Yoneda, T., Lyall, R. M., Alsina, M. M., Persons, P. E., Spada, A. P., Levizki, A., Zilberstein, A., and Mundy, G. M., The antiproliferative effects of tyrosine kinase inhibitors tyrphostins on a human squamous carcinoma in vitro and in nude mice. Cancer Res., 51, 4430–4435 (1991).

    PubMed  CAS  Google Scholar 

  • Yoshida, H. N., Kuniyasu, H., Yasui, W., Kitadai, Y., Toge, T., and Tahara, E., Expression of growth factors and their receptors in human esophageal carcinomas: regulation of expression by epidermal growth factor and transforming growth factor alpha. J. Cancer Res. Clin. Oncol., 19, 401–407 (1003).

    Google Scholar 

  • Zhang, L., Gary, E., Gallik, G. E., and Donato, N. J., Apoptotic sen-sitization in non-small cell lung cancer cells through tyrosine kinase inhibition: possible role for cytokine signaling and non-receptor tyrosine kinase as regulators of caspase activation and NSCLC cell survival. Proc. Am. Assoc. Cancer Res., 42, 131 (2001).

    Google Scholar 

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  1. National Cancer Institute, National Institute of Health, Bethesda, MD, USA

    Adorjan Aszalos

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  1. Adorjan Aszalos
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Correspondence to Adorjan Aszalos.

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Aszalos, A. Specific cell-signal targets for cancer chemotherapy. Arch Pharm Res 25, 1–10 (2002). https://doi.org/10.1007/BF02975254

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  • DOI: https://doi.org/10.1007/BF02975254

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