Skip to main content
Erschienen in: Current Colorectal Cancer Reports 4/2013

01.12.2013 | Molecular Biology (S Anant, Section Editor)

Role of Apoptosis in Colon Cancer Biology, Therapy, and Prevention

verfasst von: Lin Zhang, Jian Yu

Erschienen in: Current Colorectal Cancer Reports | Ausgabe 4/2013

Einloggen, um Zugang zu erhalten

Abstract

Deregulation of apoptosis is a hallmark of human cancer and contributes to therapeutic resistance. Recent advances in cancer genomics have revealed a myriad of alterations in key pathways that directly or indirectly increase tumor cell survival. This review outlines the pathways of apoptosis in mammalian cells, and highlights the common alterations of apoptosis regulators found in colon cancer, the role of apoptosis, and underlying mechanisms in colon cancer treatment and prevention, including recent advances in investigational agents, such as kinase inhibitors, proteasome inhibitors, heat shock protein 90 inhibitors, BH3 mimetics, tumor necrosis factor related apoptosis-inducing ligand, and inhibitor of apoptosis protein antagonists. The topics also include novel concepts as well as opportunities and challenges for drug discovery and combination therapy by exploring cancer-specific genetic defects, and therefore selective induction of apoptosis in cancer cells. Although the emphasis is on colon cancer, the main theme and many of the aspects are applicable to other solid tumors.
Literatur
1.
Zurück zum Zitat Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.PubMedCrossRef Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.PubMedCrossRef
2.
Zurück zum Zitat Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.PubMedCrossRef Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.PubMedCrossRef
3.
Zurück zum Zitat Ashkenazi A. Directing cancer cells to self-destruct with pro-apoptotic receptor agonists. Nat Rev Drug Discov. 2008;7(12):1001–12.PubMedCrossRef Ashkenazi A. Directing cancer cells to self-destruct with pro-apoptotic receptor agonists. Nat Rev Drug Discov. 2008;7(12):1001–12.PubMedCrossRef
4.
Zurück zum Zitat Bagnoli M, Canevari S, Mezzanzanica D. Cellular FLICE-inhibitory protein (c-FLIP) signalling: a key regulator of receptor-mediated apoptosis in physiologic context and in cancer. Int J Biochem Cell Biol. 2010;42(2):210–3.PubMedCrossRef Bagnoli M, Canevari S, Mezzanzanica D. Cellular FLICE-inhibitory protein (c-FLIP) signalling: a key regulator of receptor-mediated apoptosis in physiologic context and in cancer. Int J Biochem Cell Biol. 2010;42(2):210–3.PubMedCrossRef
5.
Zurück zum Zitat Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26(9):1324–37.PubMedCrossRef Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26(9):1324–37.PubMedCrossRef
6.
Zurück zum Zitat Vousden KH, Prives C. Blinded by the light: the growing complexity of p53. Cell. 2009;137(3):413–31.PubMedCrossRef Vousden KH, Prives C. Blinded by the light: the growing complexity of p53. Cell. 2009;137(3):413–31.PubMedCrossRef
7.
Zurück zum Zitat Joza N, Susin SA, Daugas E, et al. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature. 2001;410(6828):549–54.PubMedCrossRef Joza N, Susin SA, Daugas E, et al. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature. 2001;410(6828):549–54.PubMedCrossRef
8.
Zurück zum Zitat Wang X, Yang C, Chai J, Shi Y, Xue D. Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science. 2002;298(5598):1587–92.PubMedCrossRef Wang X, Yang C, Chai J, Shi Y, Xue D. Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science. 2002;298(5598):1587–92.PubMedCrossRef
9.
Zurück zum Zitat •• Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz Jr LA, Kinzler KW. Cancer genome landscapes. Science. 2013;339(6127):1546–58. This review summarizes key genetic alterations from recent genomics studies on human cancers, including colorectal cancer.PubMedCrossRef •• Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz Jr LA, Kinzler KW. Cancer genome landscapes. Science. 2013;339(6127):1546–58. This review summarizes key genetic alterations from recent genomics studies on human cancers, including colorectal cancer.PubMedCrossRef
10.
Zurück zum Zitat Yu J, Zhang L. The transcriptional targets of p53 in apoptosis control. Biochem Biophys Res Commun. 2005;331(3):851–8.PubMedCrossRef Yu J, Zhang L. The transcriptional targets of p53 in apoptosis control. Biochem Biophys Res Commun. 2005;331(3):851–8.PubMedCrossRef
11.
Zurück zum Zitat Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.PubMedCrossRef Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.PubMedCrossRef
12.
Zurück zum Zitat •• McCubrey JA, Steelman LS, Kempf CR, et al. Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways. J Cell Physiol. 2011;226(11):2762–81. This review summarizes key findings on the therapeutic responses to various targeted agents and mutations in key survival pathways in human cancer, including colorectal cancer.PubMedCrossRef •• McCubrey JA, Steelman LS, Kempf CR, et al. Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways. J Cell Physiol. 2011;226(11):2762–81. This review summarizes key findings on the therapeutic responses to various targeted agents and mutations in key survival pathways in human cancer, including colorectal cancer.PubMedCrossRef
13.
Zurück zum Zitat Rampino N, Yamamoto H, Ionov Y, et al. Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science. 1997;275(5302):967–9.PubMedCrossRef Rampino N, Yamamoto H, Ionov Y, et al. Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science. 1997;275(5302):967–9.PubMedCrossRef
14.
Zurück zum Zitat Ewings KE, Wiggins CM, Cook SJ. Bim and the pro-survival Bcl-2 proteins: opposites attract. ERK repels. Cell Cycle. 2007;6(18):2236–40.PubMedCrossRef Ewings KE, Wiggins CM, Cook SJ. Bim and the pro-survival Bcl-2 proteins: opposites attract. ERK repels. Cell Cycle. 2007;6(18):2236–40.PubMedCrossRef
15.
Zurück zum Zitat Dudgeon C, Wang P, Sun X, et al. PUMA induction by FoxO3a mediates the anticancer activities of the broad-range kinase inhibitor UCN-01. Mol Cancer Ther. 2010;9(11):2893–902.PubMedCrossRef Dudgeon C, Wang P, Sun X, et al. PUMA induction by FoxO3a mediates the anticancer activities of the broad-range kinase inhibitor UCN-01. Mol Cancer Ther. 2010;9(11):2893–902.PubMedCrossRef
16.
Zurück zum Zitat Ming L, Sakaida T, Yue W, Jha A, Zhang L, Yu J. Sp1 and p73 activate PUMA following serum starvation. Carcinogenesis. 2008;29:1878–84.PubMedCrossRef Ming L, Sakaida T, Yue W, Jha A, Zhang L, Yu J. Sp1 and p73 activate PUMA following serum starvation. Carcinogenesis. 2008;29:1878–84.PubMedCrossRef
17.
Zurück zum Zitat Sun Q, Ming L, Thomas SM, et al. PUMA mediates EGFR tyrosine kinase inhibitor-induced apoptosis in head and neck cancer cells. Oncogene. 2009;18(28):2348–57.CrossRef Sun Q, Ming L, Thomas SM, et al. PUMA mediates EGFR tyrosine kinase inhibitor-induced apoptosis in head and neck cancer cells. Oncogene. 2009;18(28):2348–57.CrossRef
18.
Zurück zum Zitat •• Qiu W, Carson-Walter EB, Kuan SF, Zhang L, Yu J. PUMA suppresses intestinal tumorigenesis in mice. Cancer Res. 2009;69(12):4999–5006. This study showed that blocked apoptosis increases intestinal cancer initiation and invasiveness in mice.PubMedCrossRef •• Qiu W, Carson-Walter EB, Kuan SF, Zhang L, Yu J. PUMA suppresses intestinal tumorigenesis in mice. Cancer Res. 2009;69(12):4999–5006. This study showed that blocked apoptosis increases intestinal cancer initiation and invasiveness in mice.PubMedCrossRef
19.
Zurück zum Zitat Johnstone RW, Frew AJ, Smyth MJ. The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer. 2008;8(10):782–98.PubMedCrossRef Johnstone RW, Frew AJ, Smyth MJ. The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer. 2008;8(10):782–98.PubMedCrossRef
20.
Zurück zum Zitat Fulda S, Vucic D. Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov. 2012;11(2):109–24.PubMedCrossRef Fulda S, Vucic D. Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov. 2012;11(2):109–24.PubMedCrossRef
21.
Zurück zum Zitat Wilson TR, McLaughlin KM, McEwan M, et al. c-FLIP: a key regulator of colorectal cancer cell death. Cancer Res. 2007;67(12):5754–62.PubMedCrossRef Wilson TR, McLaughlin KM, McEwan M, et al. c-FLIP: a key regulator of colorectal cancer cell death. Cancer Res. 2007;67(12):5754–62.PubMedCrossRef
22.
Zurück zum Zitat Xiang G, Wen X, Wang H, Chen K, Liu H. Expression of X-linked inhibitor of apoptosis protein in human colorectal cancer and its correlation with prognosis. J Surg Oncol. 2009;100(8):708–12.PubMedCrossRef Xiang G, Wen X, Wang H, Chen K, Liu H. Expression of X-linked inhibitor of apoptosis protein in human colorectal cancer and its correlation with prognosis. J Surg Oncol. 2009;100(8):708–12.PubMedCrossRef
23.
Zurück zum Zitat Krajewska M, Kim H, Kim C, et al. Analysis of apoptosis protein expression in early-stage colorectal cancer suggests opportunities for new prognostic biomarkers. Clin Cancer Res. 2005;11(15):5451–61.PubMedCrossRef Krajewska M, Kim H, Kim C, et al. Analysis of apoptosis protein expression in early-stage colorectal cancer suggests opportunities for new prognostic biomarkers. Clin Cancer Res. 2005;11(15):5451–61.PubMedCrossRef
24.
Zurück zum Zitat Endo K, Kohnoe S, Watanabe A, et al. Clinical significance of Smac/DIABLO expression in colorectal cancer. Oncol Rep. 2009;21(2):351–5.PubMed Endo K, Kohnoe S, Watanabe A, et al. Clinical significance of Smac/DIABLO expression in colorectal cancer. Oncol Rep. 2009;21(2):351–5.PubMed
25.
Zurück zum Zitat Qiu W, Liu H, Sebastini A, et al. An apoptosis-independent role of SMAC in tumor suppression. Oncogene. 2013;32(19):2380–9.PubMedCrossRef Qiu W, Liu H, Sebastini A, et al. An apoptosis-independent role of SMAC in tumor suppression. Oncogene. 2013;32(19):2380–9.PubMedCrossRef
26.
27.
Zurück zum Zitat Martini M, Vecchione L, Siena S, Tejpar S, Bardelli A. Targeted therapies: how personal should we go? Nat Rev Clin Oncol. 2012;9(2):87–97.CrossRef Martini M, Vecchione L, Siena S, Tejpar S, Bardelli A. Targeted therapies: how personal should we go? Nat Rev Clin Oncol. 2012;9(2):87–97.CrossRef
28.
Zurück zum Zitat Yu J, Zhang L. PUMA, a potent killer with or without p53. Oncogene. 2008;27 Suppl 1:S71–83.PubMedCrossRef Yu J, Zhang L. PUMA, a potent killer with or without p53. Oncogene. 2008;27 Suppl 1:S71–83.PubMedCrossRef
29.
Zurück zum Zitat Qiu W, Carson-Walter EB, Liu H, et al. PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell Stem Cell. 2008;2(6):576–83.PubMedCrossRef Qiu W, Carson-Walter EB, Liu H, et al. PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell Stem Cell. 2008;2(6):576–83.PubMedCrossRef
30.
Zurück zum Zitat Yu H, Shen H, Yuan Y, et al. Deletion of Puma protects hematopoietic stem cells and confers long-term survival in response to high-dose gamma-irradiation. Blood. 2010;115(17):3472–80.PubMedCrossRef Yu H, Shen H, Yuan Y, et al. Deletion of Puma protects hematopoietic stem cells and confers long-term survival in response to high-dose gamma-irradiation. Blood. 2010;115(17):3472–80.PubMedCrossRef
31.
Zurück zum Zitat Olsson M, Vakifahmetoglu H, Abruzzo PM, Hogstrand K, Grandien A, Zhivotovsky B. DISC-mediated activation of caspase-2 in DNA damage-induced apoptosis. Oncogene. 2009;28(18):1949–59.PubMedCrossRef Olsson M, Vakifahmetoglu H, Abruzzo PM, Hogstrand K, Grandien A, Zhivotovsky B. DISC-mediated activation of caspase-2 in DNA damage-induced apoptosis. Oncogene. 2009;28(18):1949–59.PubMedCrossRef
32.
Zurück zum Zitat Bunz F, Hwang PM, Torrance C, et al. Disruption of p53 in human cancer cells alters the responses to therapeutic agents. J Clin Invest. 1999;104(3):263–9.PubMedCrossRef Bunz F, Hwang PM, Torrance C, et al. Disruption of p53 in human cancer cells alters the responses to therapeutic agents. J Clin Invest. 1999;104(3):263–9.PubMedCrossRef
33.
Zurück zum Zitat Moll UM, Wolff S, Speidel D, Deppert W. Transcription-independent pro-apoptotic functions of p53. Curr Opin Cell Biol. 2005;17(6):631–6.PubMedCrossRef Moll UM, Wolff S, Speidel D, Deppert W. Transcription-independent pro-apoptotic functions of p53. Curr Opin Cell Biol. 2005;17(6):631–6.PubMedCrossRef
34.
Zurück zum Zitat Dotsch V, Bernassola F, Coutandin D, Candi E, Melino G. p63 and p73, the ancestors of p53. Cold Spring Harb Perspect Biol. 2010;2(9):a004887.PubMedCrossRef Dotsch V, Bernassola F, Coutandin D, Candi E, Melino G. p63 and p73, the ancestors of p53. Cold Spring Harb Perspect Biol. 2010;2(9):a004887.PubMedCrossRef
35.
Zurück zum Zitat Gudkov AV, Komarova EA. Pathologies associated with the p53 response. Cold Spring Harb Perspect Biol. 2010;2(7):a001180.PubMedCrossRef Gudkov AV, Komarova EA. Pathologies associated with the p53 response. Cold Spring Harb Perspect Biol. 2010;2(7):a001180.PubMedCrossRef
36.
Zurück zum Zitat Gong Y, Somwar R, Politi K, et al. Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas. PLoS Med. 2007;4(10):e294.PubMedCrossRef Gong Y, Somwar R, Politi K, et al. Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas. PLoS Med. 2007;4(10):e294.PubMedCrossRef
37.
Zurück zum Zitat Costa DB, Halmos B, Kumar A, et al. BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med. 2007;4(10):1669–79. discussion 1680.PubMedCrossRef Costa DB, Halmos B, Kumar A, et al. BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med. 2007;4(10):1669–79. discussion 1680.PubMedCrossRef
38.
Zurück zum Zitat Sordella R, Bell DW, Haber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science. 2004;305(5687):1163–7.PubMedCrossRef Sordella R, Bell DW, Haber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science. 2004;305(5687):1163–7.PubMedCrossRef
39.
Zurück zum Zitat Selvakumaran M, Yao KS, Feldman MD, O'Dwyer PJ. Antitumor effect of the angiogenesis inhibitor bevacizumab is dependent on susceptibility of tumors to hypoxia-induced apoptosis. Biochem Pharmacol. 2008;75(3):627–38.PubMedCrossRef Selvakumaran M, Yao KS, Feldman MD, O'Dwyer PJ. Antitumor effect of the angiogenesis inhibitor bevacizumab is dependent on susceptibility of tumors to hypoxia-induced apoptosis. Biochem Pharmacol. 2008;75(3):627–38.PubMedCrossRef
40.
Zurück zum Zitat Mizobe T, Ogata Y, Murakami H, et al. Efficacy of the combined use of bevacizumab and irinotecan as a postoperative adjuvant chemotherapy in colon carcinoma. Oncol Rep. 2008;20(3):517–23.PubMed Mizobe T, Ogata Y, Murakami H, et al. Efficacy of the combined use of bevacizumab and irinotecan as a postoperative adjuvant chemotherapy in colon carcinoma. Oncol Rep. 2008;20(3):517–23.PubMed
41.
Zurück zum Zitat Kargi A, Yalcin AD, Erin N, Savas B, Polat HH, Gorczynski RM. IL8 and serum soluble TRAIL levels following anti-VEGF monoclonal antibody treatment in patients with metastatic colon cancer. Clin Lab. 2012;58(5–6):501–5.PubMed Kargi A, Yalcin AD, Erin N, Savas B, Polat HH, Gorczynski RM. IL8 and serum soluble TRAIL levels following anti-VEGF monoclonal antibody treatment in patients with metastatic colon cancer. Clin Lab. 2012;58(5–6):501–5.PubMed
42.
Zurück zum Zitat Bisgin A, Kargi A, Yalcin AD, et al. Increased serum sTRAIL levels were correlated with survival in bevacizumab-treated metastatic colon cancer. BMC Cancer. 2012;12:58.PubMedCrossRef Bisgin A, Kargi A, Yalcin AD, et al. Increased serum sTRAIL levels were correlated with survival in bevacizumab-treated metastatic colon cancer. BMC Cancer. 2012;12:58.PubMedCrossRef
43.
Zurück zum Zitat Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34.PubMedCrossRef Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34.PubMedCrossRef
44.
Zurück zum Zitat Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.PubMedCrossRef Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.PubMedCrossRef
45.
Zurück zum Zitat Yu C, Bruzek LM, Meng XW, et al. The role of Mcl-1 downregulation in the proapoptotic activity of the multikinase inhibitor BAY 43–9006. Oncogene. 2005;24(46):6861–9.PubMedCrossRef Yu C, Bruzek LM, Meng XW, et al. The role of Mcl-1 downregulation in the proapoptotic activity of the multikinase inhibitor BAY 43–9006. Oncogene. 2005;24(46):6861–9.PubMedCrossRef
46.
Zurück zum Zitat Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006;66(24):11851–8.PubMedCrossRef Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006;66(24):11851–8.PubMedCrossRef
47.
Zurück zum Zitat • Dudgeon C, Peng R, Wang P, Sebastiani A, Yu J, Zhang L. Inhibiting oncogenic signaling by sorafenib activates PUMA via GSK3β and NF-κB to suppress tumor cell growth. Oncogene. 2012;31:4848–58. This study showed that sorafenib induces apoptosis in colon cancer cells by inducing the BH3-only protein PUMA through the NF-κB pathway.PubMedCrossRef • Dudgeon C, Peng R, Wang P, Sebastiani A, Yu J, Zhang L. Inhibiting oncogenic signaling by sorafenib activates PUMA via GSK3β and NF-κB to suppress tumor cell growth. Oncogene. 2012;31:4848–58. This study showed that sorafenib induces apoptosis in colon cancer cells by inducing the BH3-only protein PUMA through the NF-κB pathway.PubMedCrossRef
48.
Zurück zum Zitat Zhang W, Konopleva M, Ruvolo VR, et al. Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway. Leukemia. 2008;22(4):808–18.PubMedCrossRef Zhang W, Konopleva M, Ruvolo VR, et al. Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway. Leukemia. 2008;22(4):808–18.PubMedCrossRef
49.
Zurück zum Zitat Mao M, Tian F, Mariadason JM, et al. Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents. Clin Cancer Res. 2013;19(3):657–67.PubMedCrossRef Mao M, Tian F, Mariadason JM, et al. Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents. Clin Cancer Res. 2013;19(3):657–67.PubMedCrossRef
50.
Zurück zum Zitat Greger JG, Eastman SD, Zhang V, et al. Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther. 2012;11(4):909–20.PubMedCrossRef Greger JG, Eastman SD, Zhang V, et al. Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther. 2012;11(4):909–20.PubMedCrossRef
51.
Zurück zum Zitat • Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012;483(7387):100–3. This study showed that insensitivity of colon cancer to the BRAF inhibitor vemurafenib is caused by feedback activation of EGFR and can be overcome by EGFR inhibitors.PubMedCrossRef • Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012;483(7387):100–3. This study showed that insensitivity of colon cancer to the BRAF inhibitor vemurafenib is caused by feedback activation of EGFR and can be overcome by EGFR inhibitors.PubMedCrossRef
52.
Zurück zum Zitat Sun J, Sun Q, Brown MF, et al. The multi-targeted kinase inhibitor sunitinib induces apoptosis in colon cancer cells via PUMA. PLoS One. 2012;7(8):e43158.PubMedCrossRef Sun J, Sun Q, Brown MF, et al. The multi-targeted kinase inhibitor sunitinib induces apoptosis in colon cancer cells via PUMA. PLoS One. 2012;7(8):e43158.PubMedCrossRef
53.
Zurück zum Zitat • Zheng X, He K, Zhang L, Yu J. Crizotinib induces PUMA-dependent apoptosis in colon cancer cells. Mol Cancer Ther. 2013;12(5):777–86. This study showed that the MET/anaplastic lymphoma kinase inhibitor crizotinib promotes PUMA-dependent apoptosis through both p53-dependent and p53-independent mechanisms in colon cancer cells.PubMedCrossRef • Zheng X, He K, Zhang L, Yu J. Crizotinib induces PUMA-dependent apoptosis in colon cancer cells. Mol Cancer Ther. 2013;12(5):777–86. This study showed that the MET/anaplastic lymphoma kinase inhibitor crizotinib promotes PUMA-dependent apoptosis through both p53-dependent and p53-independent mechanisms in colon cancer cells.PubMedCrossRef
54.
Zurück zum Zitat Yu J, Tiwari S, Steiner P, Zhang L. Differential apoptotic response to the proteasome inhibitor bortezomib (VELCADETM, PS-341) in Bax-deficient and p21-deficient colon cancer cells. Cancer Biol Ther. 2003;2(6):694–9.PubMed Yu J, Tiwari S, Steiner P, Zhang L. Differential apoptotic response to the proteasome inhibitor bortezomib (VELCADETM, PS-341) in Bax-deficient and p21-deficient colon cancer cells. Cancer Biol Ther. 2003;2(6):694–9.PubMed
55.
Zurück zum Zitat Milano A, Iaffaioli RV, Caponigro F. The proteasome: a worthwhile target for the treatment of solid tumours? Eur J Cancer. 2007;43(7):1125–33.PubMedCrossRef Milano A, Iaffaioli RV, Caponigro F. The proteasome: a worthwhile target for the treatment of solid tumours? Eur J Cancer. 2007;43(7):1125–33.PubMedCrossRef
56.
Zurück zum Zitat Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res. 2012;18(1):64–76.PubMedCrossRef Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res. 2012;18(1):64–76.PubMedCrossRef
57.
Zurück zum Zitat Vaseva AV, Yallowitz AR, Marchenko ND, Xu S, Moll UM. Blockade of Hsp90 by 17AAG antagonizes MDMX and synergizes with nutlin to induce p53-mediated apoptosis in solid tumors. Cell Death Dis. 2011;2:e156.PubMedCrossRef Vaseva AV, Yallowitz AR, Marchenko ND, Xu S, Moll UM. Blockade of Hsp90 by 17AAG antagonizes MDMX and synergizes with nutlin to induce p53-mediated apoptosis in solid tumors. Cell Death Dis. 2011;2:e156.PubMedCrossRef
58.
Zurück zum Zitat Lippman SM. The future of molecular-targeted cancer chemoprevention. Gastroenterology. 2008;135(6):1834–41.PubMedCrossRef Lippman SM. The future of molecular-targeted cancer chemoprevention. Gastroenterology. 2008;135(6):1834–41.PubMedCrossRef
59.
60.
Zurück zum Zitat Gupta RA, Dubois RN. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer. 2001;1(1):11–21.PubMedCrossRef Gupta RA, Dubois RN. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer. 2001;1(1):11–21.PubMedCrossRef
61.
Zurück zum Zitat Sun SY, Hail Jr N, Lotan R. Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst. 2004;96(9):662–72.PubMedCrossRef Sun SY, Hail Jr N, Lotan R. Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst. 2004;96(9):662–72.PubMedCrossRef
62.
Zurück zum Zitat Zhang L, Yu J, Park BH, Kinzler KW, Vogelstein B. Role of BAX in the apoptotic response to anticancer agents. Science. 2000;290(5493):989–92.PubMedCrossRef Zhang L, Yu J, Park BH, Kinzler KW, Vogelstein B. Role of BAX in the apoptotic response to anticancer agents. Science. 2000;290(5493):989–92.PubMedCrossRef
63.
Zurück zum Zitat Kohli M, Yu J, Seaman C, et al. SMAC/Diablo-dependent apoptosis induced by nonsteroidal antiinflammatory drugs (NSAIDs) in colon cancer cells. Proc Natl Acad Sci U S A. 2004;101(48):16897–902.PubMedCrossRef Kohli M, Yu J, Seaman C, et al. SMAC/Diablo-dependent apoptosis induced by nonsteroidal antiinflammatory drugs (NSAIDs) in colon cancer cells. Proc Natl Acad Sci U S A. 2004;101(48):16897–902.PubMedCrossRef
64.
Zurück zum Zitat Bank A, Wang P, Du C, Yu J, Zhang L. SMAC mimetics sensitize nonsteroidal anti-inflammatory drug-induced apoptosis by promoting caspase-3-mediated cytochrome c release. Cancer Res. 2008;68(1):276–84.PubMedCrossRef Bank A, Wang P, Du C, Yu J, Zhang L. SMAC mimetics sensitize nonsteroidal anti-inflammatory drug-induced apoptosis by promoting caspase-3-mediated cytochrome c release. Cancer Res. 2008;68(1):276–84.PubMedCrossRef
65.
Zurück zum Zitat •• Qiu W, Wang X, Leibowitz B, et al. Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis. Proc Natl Acad Sci U S A. 2010;107(46):20027–32. This study used a mouse tumor model to show that intestinal stem cells containing gatekeeper mutations are the key target for chemoprevention.PubMedCrossRef •• Qiu W, Wang X, Leibowitz B, et al. Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis. Proc Natl Acad Sci U S A. 2010;107(46):20027–32. This study used a mouse tumor model to show that intestinal stem cells containing gatekeeper mutations are the key target for chemoprevention.PubMedCrossRef
66.
Zurück zum Zitat Meyskens Jr FL, McLaren CE, Pelot D, et al. Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prev Res (Phila). 2008;1(1):32–8.CrossRef Meyskens Jr FL, McLaren CE, Pelot D, et al. Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prev Res (Phila). 2008;1(1):32–8.CrossRef
67.
Zurück zum Zitat Barker N, Ridgway RA, van Es JH, et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2008;457(7229):608–11.PubMedCrossRef Barker N, Ridgway RA, van Es JH, et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2008;457(7229):608–11.PubMedCrossRef
68.
69.
Zurück zum Zitat Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22(2):124–31.PubMedCrossRef Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22(2):124–31.PubMedCrossRef
70.
Zurück zum Zitat Degenhardt K, Mathew R, Beaudoin B, et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell. 2006;10(1):51–64.PubMedCrossRef Degenhardt K, Mathew R, Beaudoin B, et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell. 2006;10(1):51–64.PubMedCrossRef
71.
Zurück zum Zitat White E, DiPaola RS. The double-edged sword of autophagy modulation in cancer. Clin Cancer Res. 2009;15(17):5308–16.PubMedCrossRef White E, DiPaola RS. The double-edged sword of autophagy modulation in cancer. Clin Cancer Res. 2009;15(17):5308–16.PubMedCrossRef
72.
Zurück zum Zitat Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8(9):741–52.PubMedCrossRef Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8(9):741–52.PubMedCrossRef
73.
Zurück zum Zitat Oberstein A, Jeffrey PD, Shi Y. Crystal structure of the Bcl-XL-beclin 1 peptide complex: beclin 1 is a novel BH3-only protein. J Biol Chem. 2007;282(17):13123–32.PubMedCrossRef Oberstein A, Jeffrey PD, Shi Y. Crystal structure of the Bcl-XL-beclin 1 peptide complex: beclin 1 is a novel BH3-only protein. J Biol Chem. 2007;282(17):13123–32.PubMedCrossRef
74.
Zurück zum Zitat Pattingre S, Tassa A, Qu X, et al. Bcl-2 antiapoptotic proteins inhibit beclin 1-dependent autophagy. Cell. 2005;122(6):927–39.PubMedCrossRef Pattingre S, Tassa A, Qu X, et al. Bcl-2 antiapoptotic proteins inhibit beclin 1-dependent autophagy. Cell. 2005;122(6):927–39.PubMedCrossRef
75.
Zurück zum Zitat Yousefi S, Perozzo R, Schmid I, et al. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol. 2006;8(10):1124–32.PubMedCrossRef Yousefi S, Perozzo R, Schmid I, et al. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol. 2006;8(10):1124–32.PubMedCrossRef
76.
Zurück zum Zitat Djavaheri-Mergny M, Maiuri MC, Kroemer G. Cross talk between apoptosis and autophagy by caspase-mediated cleavage of beclin 1. Oncogene. 2010;29(12):1717–9.PubMedCrossRef Djavaheri-Mergny M, Maiuri MC, Kroemer G. Cross talk between apoptosis and autophagy by caspase-mediated cleavage of beclin 1. Oncogene. 2010;29(12):1717–9.PubMedCrossRef
77.•
Zurück zum Zitat Li H, Wang P, Sun Q, et al. Following cytochrome c release, autophagy is inhibited during chemotherapy-induced apoptosis by caspase 8-mediated cleavage of beclin 1. Cancer Res. 2011;71(10):3625–34. This study used a knock-in approach to demonstrate a cross-talk mechanism between chemotherapy-induced apoptosis and autophagy.PubMedCrossRef Li H, Wang P, Sun Q, et al. Following cytochrome c release, autophagy is inhibited during chemotherapy-induced apoptosis by caspase 8-mediated cleavage of beclin 1. Cancer Res. 2011;71(10):3625–34. This study used a knock-in approach to demonstrate a cross-talk mechanism between chemotherapy-induced apoptosis and autophagy.PubMedCrossRef
78.
Zurück zum Zitat Wang L, Du F, Wang X. TNF-alpha induces two distinct caspase-8 activation pathways. Cell. 2008;133(4):693–703.PubMedCrossRef Wang L, Du F, Wang X. TNF-alpha induces two distinct caspase-8 activation pathways. Cell. 2008;133(4):693–703.PubMedCrossRef
79.
Zurück zum Zitat Petersen SL, Wang L, Yalcin-Chin A, et al. Autocrine TNFα signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis. Cancer Cell. 2007;12(5):445–56.PubMedCrossRef Petersen SL, Wang L, Yalcin-Chin A, et al. Autocrine TNFα signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis. Cancer Cell. 2007;12(5):445–56.PubMedCrossRef
80.
Zurück zum Zitat Kaiser WJ, Upton JW, Long AB, et al. RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature. 2011;471(7338):368–72.PubMedCrossRef Kaiser WJ, Upton JW, Long AB, et al. RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature. 2011;471(7338):368–72.PubMedCrossRef
81.
Zurück zum Zitat •• Oberst A, Dillon CP, Weinlich R, et al. Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature. 2011;471(7338):363–7. This study provided mechanistic insight into how apoptosis and programmed necrosis are co-regulated, sharing components of the extrinsic apoptotic pathway.PubMedCrossRef •• Oberst A, Dillon CP, Weinlich R, et al. Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature. 2011;471(7338):363–7. This study provided mechanistic insight into how apoptosis and programmed necrosis are co-regulated, sharing components of the extrinsic apoptotic pathway.PubMedCrossRef
82.
Zurück zum Zitat Zhang L, Ming L, Yu J. BH3 mimetics to improve cancer therapy; mechanisms and examples. Drug Resist Updates. 2007;10(6):207–17.CrossRef Zhang L, Ming L, Yu J. BH3 mimetics to improve cancer therapy; mechanisms and examples. Drug Resist Updates. 2007;10(6):207–17.CrossRef
83.
Zurück zum Zitat Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435(7042):677–81.PubMedCrossRef Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435(7042):677–81.PubMedCrossRef
84.
Zurück zum Zitat van Delft MF, Wei AH, Mason KD, et al. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell. 2006;10(5):389–99.PubMedCrossRef van Delft MF, Wei AH, Mason KD, et al. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell. 2006;10(5):389–99.PubMedCrossRef
85.
Zurück zum Zitat Tse C, Shoemaker AR, Adickes J, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008;68(9):3421–8.PubMedCrossRef Tse C, Shoemaker AR, Adickes J, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008;68(9):3421–8.PubMedCrossRef
86.
Zurück zum Zitat Wang S. Design of small-molecule Smac mimetics as IAP antagonists. Curr Top Microbiol Immunol. 2011;348:89–113.PubMedCrossRef Wang S. Design of small-molecule Smac mimetics as IAP antagonists. Curr Top Microbiol Immunol. 2011;348:89–113.PubMedCrossRef
87.
Zurück zum Zitat Sun Q, Zheng X, Zhang L, Yu J. Smac modulates chemosensitivity in head and neck cancer cells through the mitochondrial apoptotic pathway. Clin Cancer Res. 2011;17(8):2361–72.PubMedCrossRef Sun Q, Zheng X, Zhang L, Yu J. Smac modulates chemosensitivity in head and neck cancer cells through the mitochondrial apoptotic pathway. Clin Cancer Res. 2011;17(8):2361–72.PubMedCrossRef
88.
Zurück zum Zitat Hartwell LH, Szankasi P, Roberts CJ, Murray AW, Friend SH. Integrating genetic approaches into the discovery of anticancer drugs. Science. 1997;278(5340):1064–8.PubMedCrossRef Hartwell LH, Szankasi P, Roberts CJ, Murray AW, Friend SH. Integrating genetic approaches into the discovery of anticancer drugs. Science. 1997;278(5340):1064–8.PubMedCrossRef
89.
Zurück zum Zitat Luo J, Emanuele MJ, Li D, et al. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell. 2009;137(5):835–48.PubMedCrossRef Luo J, Emanuele MJ, Li D, et al. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell. 2009;137(5):835–48.PubMedCrossRef
90.
Zurück zum Zitat Scholl C, Frohling S, Dunn IF, et al. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell. 2009;137(5):821–34.PubMedCrossRef Scholl C, Frohling S, Dunn IF, et al. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell. 2009;137(5):821–34.PubMedCrossRef
91.
Zurück zum Zitat Singh A, Sweeney MF, Yu M, et al. TAK1 inhibition promotes apoptosis in KRAS-dependent colon cancers. Cell. 2012;148(4):639–50.PubMedCrossRef Singh A, Sweeney MF, Yu M, et al. TAK1 inhibition promotes apoptosis in KRAS-dependent colon cancers. Cell. 2012;148(4):639–50.PubMedCrossRef
92.
Zurück zum Zitat Steckel M, Molina-Arcas M, Weigelt B, et al. Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies. Cell Res. 2012;22(8):1227–45.PubMedCrossRef Steckel M, Molina-Arcas M, Weigelt B, et al. Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies. Cell Res. 2012;22(8):1227–45.PubMedCrossRef
93.
Zurück zum Zitat • Corcoran RB, Cheng KA, Hata AN, et al. Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell. 2013;23(1):121–8. This study showed that co-targeting Bcl-XL and MEK triggered a synthetic lethal interaction in KRAS mutant colorectal tumors.PubMedCrossRef • Corcoran RB, Cheng KA, Hata AN, et al. Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell. 2013;23(1):121–8. This study showed that co-targeting Bcl-XL and MEK triggered a synthetic lethal interaction in KRAS mutant colorectal tumors.PubMedCrossRef
94.
Zurück zum Zitat Yang D, Liu H, Goga A, Kim S, Yuneva M, Bishop JM. Therapeutic potential of a synthetic lethal interaction between the MYC proto-oncogene and inhibition of aurora-B kinase. Proc Natl Acad Sci U S A. 2010;107(31):13836–41.PubMedCrossRef Yang D, Liu H, Goga A, Kim S, Yuneva M, Bishop JM. Therapeutic potential of a synthetic lethal interaction between the MYC proto-oncogene and inhibition of aurora-B kinase. Proc Natl Acad Sci U S A. 2010;107(31):13836–41.PubMedCrossRef
95.
Zurück zum Zitat Wang Y, Quon KC, Knee DA, Nesterov A, Kraft AS. RAS, MYC, and sensitivity to tumor necrosis factor-alpha-related apoptosis-inducing ligand-induced apoptosis. Cancer Res. 2005;65(4):1615–6. author reply 1616–7.PubMedCrossRef Wang Y, Quon KC, Knee DA, Nesterov A, Kraft AS. RAS, MYC, and sensitivity to tumor necrosis factor-alpha-related apoptosis-inducing ligand-induced apoptosis. Cancer Res. 2005;65(4):1615–6. author reply 1616–7.PubMedCrossRef
96.
Zurück zum Zitat Nieminen AI, Partanen JI, Hau A, Klefstrom J. c-Myc primed mitochondria determine cellular sensitivity to TRAIL-induced apoptosis. EMBO J. 2007;26(4):1055–67.PubMedCrossRef Nieminen AI, Partanen JI, Hau A, Klefstrom J. c-Myc primed mitochondria determine cellular sensitivity to TRAIL-induced apoptosis. EMBO J. 2007;26(4):1055–67.PubMedCrossRef
97.
Zurück zum Zitat Ashworth A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol. 2008;26(22):3785–90.PubMedCrossRef Ashworth A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol. 2008;26(22):3785–90.PubMedCrossRef
98.
Zurück zum Zitat Martin SA, McCabe N, Mullarkey M, et al. DNA polymerases as potential therapeutic targets for cancers deficient in the DNA mismatch repair proteins MSH2 or MLH1. Cancer Cell. 2010;17(3):235–48.PubMedCrossRef Martin SA, McCabe N, Mullarkey M, et al. DNA polymerases as potential therapeutic targets for cancers deficient in the DNA mismatch repair proteins MSH2 or MLH1. Cancer Cell. 2010;17(3):235–48.PubMedCrossRef
99.
Zurück zum Zitat Martin SA, Hewish M, Sims D, Lord CJ, Ashworth A. Parallel high-throughput RNA interference screens identify PINK1 as a potential therapeutic target for the treatment of DNA mismatch repair-deficient cancers. Cancer Res. 2011;71(5):1836–48.PubMedCrossRef Martin SA, Hewish M, Sims D, Lord CJ, Ashworth A. Parallel high-throughput RNA interference screens identify PINK1 as a potential therapeutic target for the treatment of DNA mismatch repair-deficient cancers. Cancer Res. 2011;71(5):1836–48.PubMedCrossRef
100.
Zurück zum Zitat • Chan DA, Giaccia AJ. Harnessing synthetic lethal interactions in anticancer drug discovery. Nat Rev Drug Discov. 2011;10(5):351–64. This review discusses the potential use of synthetic lethal interactions for discovery of new anticancer drugs.PubMedCrossRef • Chan DA, Giaccia AJ. Harnessing synthetic lethal interactions in anticancer drug discovery. Nat Rev Drug Discov. 2011;10(5):351–64. This review discusses the potential use of synthetic lethal interactions for discovery of new anticancer drugs.PubMedCrossRef
Metadaten
Titel
Role of Apoptosis in Colon Cancer Biology, Therapy, and Prevention
verfasst von
Lin Zhang
Jian Yu
Publikationsdatum
01.12.2013
Verlag
Springer US
Erschienen in
Current Colorectal Cancer Reports / Ausgabe 4/2013
Print ISSN: 1556-3790
Elektronische ISSN: 1556-3804
DOI
https://doi.org/10.1007/s11888-013-0188-z

Weitere Artikel der Ausgabe 4/2013

Current Colorectal Cancer Reports 4/2013 Zur Ausgabe

Immunotherapy of Malignancy (MA Morse, Section Editor)

Modulation of Immune System Inhibitory Checkpoints in Colorectal Cancer

Translational Colorectal Oncology (Y Jiang, Section Editor)

How Do We Make Choices in Salvage Therapy: Panitumumab, Cetuximab, or Regorafenib?

Translational Colorectal Oncology (Y Jiang, Section Editor)

Oncotype DX for Colon Cancer: Are We Ready for Prime Time in Personalized Medicine?

Molecular Biology (S Anant, Section Editor)

Honokiol as a Radiosensitizing Agent for Colorectal Cancers

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

So sicher sind Tattoos: Neue Daten zur Risikobewertung

22.05.2024 Melanom Nachrichten

Das größte medizinische Problem bei Tattoos bleiben allergische Reaktionen. Melanome werden dadurch offensichtlich nicht gefördert, die Farbpigmente könnten aber andere Tumoren begünstigen.

CAR-M-Zellen: Warten auf das große Fressen

22.05.2024 Onkologische Immuntherapie Nachrichten

Auch myeloide Immunzellen lassen sich mit chimären Antigenrezeptoren gegen Tumoren ausstatten. Solche CAR-Fresszell-Therapien werden jetzt für solide Tumoren entwickelt. Künftig soll dieser Prozess nicht mehr ex vivo, sondern per mRNA im Körper der Betroffenen erfolgen.

Blutdrucksenkung könnte Uterusmyome verhindern

Frauen mit unbehandelter oder neu auftretender Hypertonie haben ein deutlich erhöhtes Risiko für Uterusmyome. Eine Therapie mit Antihypertensiva geht hingegen mit einer verringerten Inzidenz der gutartigen Tumoren einher.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.