Advances in the Application of Apoptotic Proteins and Alternative Splicing in Tumor Therapy: A Narrative Review
-
Jin He
,
Weitao Qiu
,
Yonghong Li
,
Chaojun Wei
,
Zhongtian Bai
,
Jing Jia
,
Hui Cai
Abstract
An apoptosis-resistant state determined by apoptotic protein expression is commonly seen in the initiation, progression, and treatment failure stages of human cancer, and anti-tumor drugs targeting apoptotic proteins have been increasingly developed over the past three decades. However, the frequently alternative splicing of apoptotic proteins diminished the ability of targeting drugs to bind to apoptotic proteins and, consequently, limit the drug efficacy. Currently, accumulating evidence has demonstrated that many alternative splicing events have been associated to apoptosis resistance in different cancers. Therefore, the intervention targeting alternative splicing for regulating tumor cell apoptosis is expected to become a new strategy and new direction of antitumor therapy. Here, we present well established alternative splicing events that occur in different apoptosis-related genes and their modification by several approaches with cancer therapeutic purposes.
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2. Ichim G, Tait S (2016). A fate worse than death: apoptosis as an oncogenic process. Nat Rev Cancer, 16(8):539-48.
3. Carneiro B, El-Deiry W (2020). Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol, 17(7):395-417.
4. Pentimalli F, Grelli S, Di Daniele N, Melino G, Amelio I (2019). Cell death pathologies: targeting death pathways and the immune system for cancer therapy. Genes Immun, 20:539-554.
5. MacFarlane M (2003). TRAIL-induced signalling and apoptosis. Toxicol Lett, 139(2-3):89-97.
6. Pećina-Slaus N (2009). [Genetic and molecular insights into apoptosis]. Acta Med Croatica ,2:13-9.
7. Kalkavan H, Green D (2018). MOMP, cell suicide as a BCL-2 family business. Cell Death Differ, 25(1):46-55.
8. Singh R, Letai A, Sarosiek K (2019). Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nature Reviews Molecular Cell Biology, 20:175-193.
9. Yuan X, Gajan A, Chu Q, Xiong H, Wu K, Wu G (2018). Developing TRAIL/TRAIL death receptor-based cancer therapies. Cancer Metastasis Rev, 37(4):733-748.
10. Emery J, McDonnell P, Burke M, et al (1998). Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem, 273(23):14363-7.
11. Falschlehner C, Ganten T, Koschny R, Schaefer U, Walczak H (2009). TRAIL and other TRAIL receptor agonists as novel cancer therapeutics. Adv Exp Med Biol, 647:195-206.
12. Herbst R, Kurzrock R, Hong D, et al (2010). A first-in-human study of conatumumab in adult patients with advanced solid tumors. Clin Cancer Res ,16(23):5883-91.
13. Amm H, Oliver P, Lee C, Li Y, Buchsbaum D (2011). Combined modality therapy with TRAIL or agonistic death receptor antibodies. Cancer Biol Ther, 11(5):431-49.
14. Quintavalle C, Condorelli G (2012). Dulanermin in cancer therapy: still much to do. Transl Lung Cancer Res, 1(2):158-9.
15. Ralff M, Kline C, Küçükkase O, et al (2017). ONC201 Demonstrates Antitumor Effects in Both Triple-Negative and Non-Triple-Negative Breast Cancers through TRAIL-Dependent and TRAIL-Independent Mechanisms. Mol Cancer Ther, 16(7):1290-1298.
16. Wang J, Wang H, Wang L, et al (2016). Silencing the epigenetic silencer KDM4A for TRAIL and DR5 simultaneous induction and antitumor therapy. Cell Death Differ, 23(11):1886-1896.
17. Wagner J, Kline C, Zhou L, et al (2018). Dose intensification of TRAIL-inducing ONC201 inhibits metastasis and promotes intratumoral NK cell recruitment. J Clin Invest, 128(6):2325-2338.
18. Stein M, Malhotra J, Tarapore R, et al (2019). Safety and enhanced immunostimulatory activity of the DRD2 antagonist ONC201 in advanced solid tumor patients with weekly oral administration. J Immunother Cancer, 7(1):136.
19. Park J, Oh Y, Park Y, et al (2019). Targeting of dermal myofibroblasts through death receptor 5 arrests fibrosis in mouse models of scleroderma. Nat Commun, 10(1):1128.
20. Holland P (2014). Death receptor agonist therapies for cancer, which is the right TRAIL? Cytokine Growth Factor Rev, 25(2):185-93.
21. Zhang S, Zheng C, Zhu W, et al (2019). A novel anti-DR5 antibody-drug conjugate possesses a high-potential therapeutic efficacy for leukemia and solid tumors. Theranostics, 9(18):5412-5423.
22. Dubuisson A, Favreau C, Fourmaux E, et al (2019). Generation and characterization of novel anti-DR4 and anti-DR5 antibodies developed by genetic immunization. Cell Death Dis, 10(2):101.
23. Brünker P, Wartha K, Friess T,et al (2016). RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis. Mol Cancer Ther, 15(5):946-57.
24. Milutinovic S, Kashyap A, Yanagi T, et al (2016). Dual Agonist Surrobody Simultaneously Activates Death Receptors DR4 and DR5 to Induce Cancer Cell Death. Mol Cancer Ther, 15(1):114-24.
25. von Pawel J, Harvey J, Spigel D,et al (2014). Phase II trial of mapatumumab, a fully human agonist monoclonal antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1), in combination with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer. Clin Lung Cancer, 15(3):188-196.e2.
26. Hotte S, Hirte H, Chen E, et al (2008). A phase 1 study of mapatumumab (fully human monoclonal antibody to TRAIL-R1) in patients with advanced solid malignancies. Clin Cancer Res , 14(11):3450-5.
27. Plummer R, Attard G, Pacey S, et al (2007). Phase 1 and pharmacokinetic study of lexatumumab in patients with advanced cancers. Clin Cancer Res, 13(20):6187-94.
28. Smith M, Jin F, Joshi I (2007). Bortezomib sensitizes non-Hodgkin's lymphoma cells to apoptosis induced by antibodies to tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors TRAIL-R1 and TRAIL-R2. Clin Cancer Res ,13(18 Pt 2):5528s-5534s.
29. Paz-Ares L, Bálint B, de Boer R, et al (2013). A randomized phase 2 study of paclitaxel and carboplatin with or without conatumumab for first-line treatment of advanced non-small-cell lung cancer. J Thorac Oncol, 8(3):329-37.
30. Oltersdorf T, Elmore S, Shoemaker A,et al (2005). An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature, 435(7042):677-81.
31. Del Gaizo Moore V, Brown J, Certo M, Love T, Novina C, Letai A (2007). Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest, 117(1):112-21.
32. Roberts A, Seymour J, Brown J, et al (2012). Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 30:488-96.
33. Fischer K, Al-Sawaf O, Bahlo J, et al (2019). Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. N Engl J Med, 380(23):2225-2236.
34. Seymour J, Kipps T, Eichhorst B, et al (2018). Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med, 378(12):1107-1120.
35. Xin M, Li R, Xie M, et al (2014). Small-molecule Bax agonists for cancer therapy. Nat Commun, 5:4935.
36. Li R, Ding C, Zhang J, et al (2017). Modulation of Bax and mTOR for Cancer Therapeutics. Cancer Res, 77(11):3001-3012.
37. Gavathiotis E, Reyna D, Bellairs J, Leshchiner E, Walensky L (2012). Direct and selective small-molecule activation of proapoptotic BAX. Nat Chem Biol, 8(7):639-45.
38. Reyna D, Garner T, Lopez A, et al (2017). Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia. Cancer cell, 32(4):490-505.e10.
39. Garner T, Amgalan D, Reyna D, Li S, Kitsis R, Gavathiotis E (2019). Small-molecule allosteric inhibitors of BAX. Nat Chem Biol, 15(4):322-330.
40. Weston C, Balmanno K, Chalmers C, et al (2003). Activation of ERK1/2 by deltaRaf-1:ER* represses Bim expression independently of the JNK or PI3K pathways. Oncogene, 22(9):1281-93.
41. Xia J, Bai H, Yan B, Li R, Shao M, Xiong L, Han B (2017). Mimicking the BIM BH3 domain overcomes resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer. Oncotarget, 8(65):108522-108533.
42. Costa D, Halmos B, Kumar A, et al (2007). BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med, 4(10):1669-79; discussion 1680.
43. Ng K, Hillmer A, Chuah C, et al (2012). A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med, 18(4):521-8.
44. Prukova D, Andera L, Nahacka Z,et al (2019). In VivoCotargeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal in Relapsed Mantle Cell Lymphoma. Clin Cancer Res , 25(14):4455-4465.
45. Fulda S, Vucic D (2012). Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov, 11(2):109-24.
46. Gyrd-Hansen M, Meier P (2010). IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer, 10(8):561-74.
47. Vucic D, Franklin M, Wallweber H, et al (2005). Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP. Biochem J, 385(Pt 1):11-20.
48. Tolcher A, Bendell J, Papadopoulos K, et al (2016). A Phase I Dose-Escalation Study Evaluating the Safety Tolerability and Pharmacokinetics of CUDC-427, a Potent, Oral, Monovalent IAP Antagonist, in Patients with Refractory Solid Tumors. Clin Cancer Res, 22(18):4567-73.
49. Infante J, Dees E, Olszanski A, Dhuria S, Sen S, Cameron S, Cohen R (2014). Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. J Clin Oncol, 32(28):3103-10.
50. Sas-Chen A, Aure M, Leibovich L, et al (2016). LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer. EMBO Mol Med, 8(9):1052-64.
51. Kim E, Ilagan J, Liang Y, et al (2015). SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition. Cancer Cell, 27(5):617-30.
52. Chang J, Yang D, Chang W, et al (2011). Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells. PLoS One, 6(6):e18643.
53. Kaida D, Motoyoshi H, Tashiro E, et al (2007). Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol, 3(9):576-83.
54. Pham D, Koide K (2016). Discoveries, target identifications, and biological applications of natural products that inhibit splicing factor 3B subunit 1. Natural Product Reports, 33:637-47.
55. McClorey G, Wood M (2015). An overview of the clinical application of antisense oligonucleotides for RNA-targeting therapies. Curr Opin Pharmacol, 24:52-8.
56. Castanotto D, Stein C (2014). Antisense oligonucleotides in cancer. Curr Opin Oncol, 26(6):584-9.
57. Hua Y, Vickers T, Okunola H, Bennett C, Krainer A (2008). Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am J Hum Genet, 82(4):834-48.
58. Stevens M, Oltean S (2019). Modulation of the Apoptosis Gene Bcl-x Function Through Alternative Splicing. Front Genet, 10:804.
59. Dewaele M, Tabaglio T, Willekens K, et al (2016). Antisense oligonucleotide-mediated MDM4 exon 6 skipping impairs tumor growth. J Clin Invest, 126(1):68-84.
2. Ichim G, Tait S (2016). A fate worse than death: apoptosis as an oncogenic process. Nat Rev Cancer, 16(8):539-48.
3. Carneiro B, El-Deiry W (2020). Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol, 17(7):395-417.
4. Pentimalli F, Grelli S, Di Daniele N, Melino G, Amelio I (2019). Cell death pathologies: targeting death pathways and the immune system for cancer therapy. Genes Immun, 20:539-554.
5. MacFarlane M (2003). TRAIL-induced signalling and apoptosis. Toxicol Lett, 139(2-3):89-97.
6. Pećina-Slaus N (2009). [Genetic and molecular insights into apoptosis]. Acta Med Croatica ,2:13-9.
7. Kalkavan H, Green D (2018). MOMP, cell suicide as a BCL-2 family business. Cell Death Differ, 25(1):46-55.
8. Singh R, Letai A, Sarosiek K (2019). Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nature Reviews Molecular Cell Biology, 20:175-193.
9. Yuan X, Gajan A, Chu Q, Xiong H, Wu K, Wu G (2018). Developing TRAIL/TRAIL death receptor-based cancer therapies. Cancer Metastasis Rev, 37(4):733-748.
10. Emery J, McDonnell P, Burke M, et al (1998). Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem, 273(23):14363-7.
11. Falschlehner C, Ganten T, Koschny R, Schaefer U, Walczak H (2009). TRAIL and other TRAIL receptor agonists as novel cancer therapeutics. Adv Exp Med Biol, 647:195-206.
12. Herbst R, Kurzrock R, Hong D, et al (2010). A first-in-human study of conatumumab in adult patients with advanced solid tumors. Clin Cancer Res ,16(23):5883-91.
13. Amm H, Oliver P, Lee C, Li Y, Buchsbaum D (2011). Combined modality therapy with TRAIL or agonistic death receptor antibodies. Cancer Biol Ther, 11(5):431-49.
14. Quintavalle C, Condorelli G (2012). Dulanermin in cancer therapy: still much to do. Transl Lung Cancer Res, 1(2):158-9.
15. Ralff M, Kline C, Küçükkase O, et al (2017). ONC201 Demonstrates Antitumor Effects in Both Triple-Negative and Non-Triple-Negative Breast Cancers through TRAIL-Dependent and TRAIL-Independent Mechanisms. Mol Cancer Ther, 16(7):1290-1298.
16. Wang J, Wang H, Wang L, et al (2016). Silencing the epigenetic silencer KDM4A for TRAIL and DR5 simultaneous induction and antitumor therapy. Cell Death Differ, 23(11):1886-1896.
17. Wagner J, Kline C, Zhou L, et al (2018). Dose intensification of TRAIL-inducing ONC201 inhibits metastasis and promotes intratumoral NK cell recruitment. J Clin Invest, 128(6):2325-2338.
18. Stein M, Malhotra J, Tarapore R, et al (2019). Safety and enhanced immunostimulatory activity of the DRD2 antagonist ONC201 in advanced solid tumor patients with weekly oral administration. J Immunother Cancer, 7(1):136.
19. Park J, Oh Y, Park Y, et al (2019). Targeting of dermal myofibroblasts through death receptor 5 arrests fibrosis in mouse models of scleroderma. Nat Commun, 10(1):1128.
20. Holland P (2014). Death receptor agonist therapies for cancer, which is the right TRAIL? Cytokine Growth Factor Rev, 25(2):185-93.
21. Zhang S, Zheng C, Zhu W, et al (2019). A novel anti-DR5 antibody-drug conjugate possesses a high-potential therapeutic efficacy for leukemia and solid tumors. Theranostics, 9(18):5412-5423.
22. Dubuisson A, Favreau C, Fourmaux E, et al (2019). Generation and characterization of novel anti-DR4 and anti-DR5 antibodies developed by genetic immunization. Cell Death Dis, 10(2):101.
23. Brünker P, Wartha K, Friess T,et al (2016). RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis. Mol Cancer Ther, 15(5):946-57.
24. Milutinovic S, Kashyap A, Yanagi T, et al (2016). Dual Agonist Surrobody Simultaneously Activates Death Receptors DR4 and DR5 to Induce Cancer Cell Death. Mol Cancer Ther, 15(1):114-24.
25. von Pawel J, Harvey J, Spigel D,et al (2014). Phase II trial of mapatumumab, a fully human agonist monoclonal antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1), in combination with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer. Clin Lung Cancer, 15(3):188-196.e2.
26. Hotte S, Hirte H, Chen E, et al (2008). A phase 1 study of mapatumumab (fully human monoclonal antibody to TRAIL-R1) in patients with advanced solid malignancies. Clin Cancer Res , 14(11):3450-5.
27. Plummer R, Attard G, Pacey S, et al (2007). Phase 1 and pharmacokinetic study of lexatumumab in patients with advanced cancers. Clin Cancer Res, 13(20):6187-94.
28. Smith M, Jin F, Joshi I (2007). Bortezomib sensitizes non-Hodgkin's lymphoma cells to apoptosis induced by antibodies to tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors TRAIL-R1 and TRAIL-R2. Clin Cancer Res ,13(18 Pt 2):5528s-5534s.
29. Paz-Ares L, Bálint B, de Boer R, et al (2013). A randomized phase 2 study of paclitaxel and carboplatin with or without conatumumab for first-line treatment of advanced non-small-cell lung cancer. J Thorac Oncol, 8(3):329-37.
30. Oltersdorf T, Elmore S, Shoemaker A,et al (2005). An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature, 435(7042):677-81.
31. Del Gaizo Moore V, Brown J, Certo M, Love T, Novina C, Letai A (2007). Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest, 117(1):112-21.
32. Roberts A, Seymour J, Brown J, et al (2012). Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 30:488-96.
33. Fischer K, Al-Sawaf O, Bahlo J, et al (2019). Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. N Engl J Med, 380(23):2225-2236.
34. Seymour J, Kipps T, Eichhorst B, et al (2018). Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med, 378(12):1107-1120.
35. Xin M, Li R, Xie M, et al (2014). Small-molecule Bax agonists for cancer therapy. Nat Commun, 5:4935.
36. Li R, Ding C, Zhang J, et al (2017). Modulation of Bax and mTOR for Cancer Therapeutics. Cancer Res, 77(11):3001-3012.
37. Gavathiotis E, Reyna D, Bellairs J, Leshchiner E, Walensky L (2012). Direct and selective small-molecule activation of proapoptotic BAX. Nat Chem Biol, 8(7):639-45.
38. Reyna D, Garner T, Lopez A, et al (2017). Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia. Cancer cell, 32(4):490-505.e10.
39. Garner T, Amgalan D, Reyna D, Li S, Kitsis R, Gavathiotis E (2019). Small-molecule allosteric inhibitors of BAX. Nat Chem Biol, 15(4):322-330.
40. Weston C, Balmanno K, Chalmers C, et al (2003). Activation of ERK1/2 by deltaRaf-1:ER* represses Bim expression independently of the JNK or PI3K pathways. Oncogene, 22(9):1281-93.
41. Xia J, Bai H, Yan B, Li R, Shao M, Xiong L, Han B (2017). Mimicking the BIM BH3 domain overcomes resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer. Oncotarget, 8(65):108522-108533.
42. Costa D, Halmos B, Kumar A, et al (2007). BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med, 4(10):1669-79; discussion 1680.
43. Ng K, Hillmer A, Chuah C, et al (2012). A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med, 18(4):521-8.
44. Prukova D, Andera L, Nahacka Z,et al (2019). In VivoCotargeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal in Relapsed Mantle Cell Lymphoma. Clin Cancer Res , 25(14):4455-4465.
45. Fulda S, Vucic D (2012). Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov, 11(2):109-24.
46. Gyrd-Hansen M, Meier P (2010). IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer, 10(8):561-74.
47. Vucic D, Franklin M, Wallweber H, et al (2005). Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP. Biochem J, 385(Pt 1):11-20.
48. Tolcher A, Bendell J, Papadopoulos K, et al (2016). A Phase I Dose-Escalation Study Evaluating the Safety Tolerability and Pharmacokinetics of CUDC-427, a Potent, Oral, Monovalent IAP Antagonist, in Patients with Refractory Solid Tumors. Clin Cancer Res, 22(18):4567-73.
49. Infante J, Dees E, Olszanski A, Dhuria S, Sen S, Cameron S, Cohen R (2014). Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. J Clin Oncol, 32(28):3103-10.
50. Sas-Chen A, Aure M, Leibovich L, et al (2016). LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer. EMBO Mol Med, 8(9):1052-64.
51. Kim E, Ilagan J, Liang Y, et al (2015). SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition. Cancer Cell, 27(5):617-30.
52. Chang J, Yang D, Chang W, et al (2011). Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells. PLoS One, 6(6):e18643.
53. Kaida D, Motoyoshi H, Tashiro E, et al (2007). Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol, 3(9):576-83.
54. Pham D, Koide K (2016). Discoveries, target identifications, and biological applications of natural products that inhibit splicing factor 3B subunit 1. Natural Product Reports, 33:637-47.
55. McClorey G, Wood M (2015). An overview of the clinical application of antisense oligonucleotides for RNA-targeting therapies. Curr Opin Pharmacol, 24:52-8.
56. Castanotto D, Stein C (2014). Antisense oligonucleotides in cancer. Curr Opin Oncol, 26(6):584-9.
57. Hua Y, Vickers T, Okunola H, Bennett C, Krainer A (2008). Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am J Hum Genet, 82(4):834-48.
58. Stevens M, Oltean S (2019). Modulation of the Apoptosis Gene Bcl-x Function Through Alternative Splicing. Front Genet, 10:804.
59. Dewaele M, Tabaglio T, Willekens K, et al (2016). Antisense oligonucleotide-mediated MDM4 exon 6 skipping impairs tumor growth. J Clin Invest, 126(1):68-84.
| Files | ||
| Issue | Vol 52 No 7 (2023) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v52i7.13233 | |
| Keywords | ||
| Apoptosis Alternative splicing Cancer Therapeutics | ||
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How to Cite
1.
He J, Qiu W, Li Y, Wei C, Bai Z, Jia J, Cai H. Advances in the Application of Apoptotic Proteins and Alternative Splicing in Tumor Therapy: A Narrative Review. Iran J Public Health. 2023;52(7):1311-1319.
