Protein Serine-Threonine Kinases as Drug Target In Cancer Treatment
Keywords:
serine-threonine kinases; cancer; targeted drug; signaling pathwayAbstract
Serine-threonine kinases (STKs) are important regulators of intracellular signaling pathways. They regulate varieties of fundamental cellular processes including growth, proliferation, protein synthesis, metabolism, aging, and apoptosis. STKs are frequently dysregulated in human cancer. It is therefore, understanding of the characteristics of these proteins and their functions in signaling cascades is essential for development of new anti-cancer drugs. In this review, some STKS which implicated as cancer-driver are mentioned in term of their features as well as their roles in carcinogenesis. Additionally, drugs targeting these STKs are also reviewed.
References
1. Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 2010; 1802: 396-405.
2. Burotto M, Chiou VL, Lee JM, Kohn EC. The MAPK pathway across different malignancies: a new perspective. Cancer 2014; 120: 3446-56.
3. Peng Q, Deng Z, Pan H, Gu L, Liu O, Tang Z. Mitogen-activated protein kinase signaling pathway in oral cancer. Oncol Lett 2018; 15: 1379-88.
4. Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer 2003; 3(6): 459-65.
5. Matallanas D, Birtwistle M, Romano D, Zebisch A, Rauch J, von Kriegsheim A, et al. Raf family kinases: old dogs have learned new tricks. Genes Cancer 2011; 2: 232-60.
6. Ahearn IM, Haigis K, Bar-Sagi D, Philips MR. Regulating the regulator: post-translational modification of RAS. Nat Rev Mol Cell Biol 2011; 13: 39-51.
7. Gkouveris I, Nikitakis N, Karanikou M, Rassidakis G, Sklavounou A. JNK1/2 expression and modulation of STAT3 signaling in oral cancer. Oncol Lett 2016; 12: 699-706.
8. Simoes AE, Rodrigues CM, Borralho PM. The MEK5/ERK5 signalling pathway in cancer: a promising novel therapeutic target. Drug Discov Today 2016; 21: 1654-63.
9. Hussain MR, Baig M, Mohamoud HS, Ulhaq Z, Hoessli DC, Khogeer GS, et al. BRAF gene: From human cancers to developmental syndromes. Saudi J Biol Sci 2015; 22: 359-73.
10. Rushworth LK, Hindley AD, O'Neill E, Kolch W. Regulation and role of Raf-1/B-Raf heterodimerization. Mol Cell Biol 2006; 26: 2262-72.
11.Braicu C, Buse M, Busuioc C, Drula R, Gulei D, Raduly L, et al. A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer. Cancers 2019; 11(10): 1618. doi: 10.3390/cancers11101618.
12. Liu F, Yang X, Geng M, Huang M. Targeting ERK, an Achilles' Heel of the MAPK pathway, in cancer therapy. Acta Pharm Sin B 2018; 8: 552-62.
13. Lee S, Rauch J, Kolch W. Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity. Int J Mol Sci 2020; 21: 1102. doi: 10.3390/ijms21031102.
14.Czirbesz K, Gorka E, Balatoni T, Panczel G, Melegh K, Kovacs P, et al. Efficacy of Vemurafenib Treatment in 43 Metastatic Melanoma Patients with BRAF Mutation. Single-Institute Retrospective Analysis, Early Real-Life Survival Data. Pathol Oncol Res 2019; 25: 45-50.
15.Takahashi A, Namikawa K, Nakano E, Yamazaki N. Real-world efficacy and safety data for dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation-positive advanced melanoma. J Dermatol 2020; 47: 257-64.
16.Trojaniello C, Festino L, Vanella V, Ascierto PA. Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations. Expert Rev Clin Pharmacol 2019; 12: 259-66.
17.Ascierto PA, McArthur GA, Dreno B, Atkinson V, Liszkay G, Di Giacomo AM, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol 2016; 17: 1248-60.
18.Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, et al. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol 2018; 36: 7-13.
19. Wang J, Zhao W, Guo H, Fang Y, Stockman SE, Bai S, et al. AKT isoform-specific expression and activation across cancer lineages. BMC cancer 2018; 18: 742.
20. Kumar CC, Madison V. AKT crystal structure and AKT-specific inhibitors. Oncogene 2005; 24: 7493-501.
21. Liao Y, Hung MC. Physiological regulation of Akt activity and stability. Am J Transl Res 2010; 2: 19-42.
22. Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer cell 2003; 4: 257-62.
23. Manning BD, Toker A. AKT/PKB Signaling: Navigating the Network. Cell 2017; 169: 381-405.
24. Kong D-x, Yamori T. ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor identified using the JFCR39 drug discovery system. Acta Pharmacologica Sinica 2010; 31: 1189-97.
25. Wendel HG, De Stanchina E, Fridman JS, Malina A, Ray S, Kogan S, et al. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature 2004; 428(6980): 332-7.
26. Chen X, Thakkar H, Tyan F, Gim S, Robinson H, Lee C, et al. Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer. Oncogene 2001; 20(42): 6073-83.
27. Bai D, Ueno L, Vogt PK. Akt-mediated regulation of NFB and the essentialness of NFB for the oncogenicity of PI3K and Akt. Int J Cancer 2009; 125(12): 2863-70.
28. Ogawara Y, Kishishita S, Obata T, Isazawa Y, Suzuki T, Tanaka K, et al. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem 2002; 277(24): 21843-50.
29. Ma YY, Wei SJ, Lin YC, Lung JC, Chang TC, Whang-Peng J, et al. PIK3CA as an oncogene in cervical cancer. Oncogene 2000; 19(23): 2739-44.
30. Hashimoto K, Mori N, Tamesa T, Okada T, Kawauchi S, Oga A, et al. Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH. Mod Pathol 2004; 17(6): 617-22.
31. Cheng JQ, Godwin AK, Bellacosa A, Taguchi T, Franke TF, Hamilton TC, et al. AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc Natl Acad Sci USA 1992; 89(19): 9267-71.
32. Miwa W, Yasuda J, Murakami Y, Yashima K, Sugano K, Sekine T, et al. Isolation of DNA Sequences Amplified at Chromosome 19q13.1–q13.2 Including theAKT2Locus in Human Pancreatic Cancer. Biochem Biophys Res Commun 1996; 225(3): 968-74.
33. Shariati M, Meric-Bernstam F. Targeting AKT for cancer therapy. Expert Opin Investig Drugs 2019; 28(11): 977-88.
34. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, et al. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 2002; 10(3): 457-68.
35. Cornu M, Albert V, Hall MN. mTOR in aging, metabolism, and cancer. Curr Opin Genet Dev 2013; 23(1): 53-62.
36. Zhao L, Vogt PK. Class I PI3K in oncogenic cellular transformation. Oncogene 2008; 27(41): 5486-96.
37. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307(5712): 1098-101.
38. Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease. Cell 2017; 168(6): 960-76.
39. Murugan AK. mTOR: Role in cancer, metastasis and drug resistance. Semin Cancer Biol 2019; 59: 92-111.
40. Russell RC, Fang C, Guan KL. An emerging role for TOR signaling in mammalian tissue and stem cell physiology. Development 2011; 138(16): 3343-56.
41. Pópulo H, Lopes JM, Soares P. The mTOR Signalling Pathway in Human Cancer. Int J Mol Sci 2012; 13(2): 1886-918.
42.Afshar M, Pascoe J, Whitmarsh S, James N, Porfiri E. Temsirolimus for patients with metastatic renal cell carcinoma: outcomes in patients receiving temsirolimus within a compassionate use program in a tertiary referral center. Drug Des Devel Ther 2015; 9: 13-9.
43.Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008; 372(9637): 449-56.
2. Burotto M, Chiou VL, Lee JM, Kohn EC. The MAPK pathway across different malignancies: a new perspective. Cancer 2014; 120: 3446-56.
3. Peng Q, Deng Z, Pan H, Gu L, Liu O, Tang Z. Mitogen-activated protein kinase signaling pathway in oral cancer. Oncol Lett 2018; 15: 1379-88.
4. Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer 2003; 3(6): 459-65.
5. Matallanas D, Birtwistle M, Romano D, Zebisch A, Rauch J, von Kriegsheim A, et al. Raf family kinases: old dogs have learned new tricks. Genes Cancer 2011; 2: 232-60.
6. Ahearn IM, Haigis K, Bar-Sagi D, Philips MR. Regulating the regulator: post-translational modification of RAS. Nat Rev Mol Cell Biol 2011; 13: 39-51.
7. Gkouveris I, Nikitakis N, Karanikou M, Rassidakis G, Sklavounou A. JNK1/2 expression and modulation of STAT3 signaling in oral cancer. Oncol Lett 2016; 12: 699-706.
8. Simoes AE, Rodrigues CM, Borralho PM. The MEK5/ERK5 signalling pathway in cancer: a promising novel therapeutic target. Drug Discov Today 2016; 21: 1654-63.
9. Hussain MR, Baig M, Mohamoud HS, Ulhaq Z, Hoessli DC, Khogeer GS, et al. BRAF gene: From human cancers to developmental syndromes. Saudi J Biol Sci 2015; 22: 359-73.
10. Rushworth LK, Hindley AD, O'Neill E, Kolch W. Regulation and role of Raf-1/B-Raf heterodimerization. Mol Cell Biol 2006; 26: 2262-72.
11.Braicu C, Buse M, Busuioc C, Drula R, Gulei D, Raduly L, et al. A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer. Cancers 2019; 11(10): 1618. doi: 10.3390/cancers11101618.
12. Liu F, Yang X, Geng M, Huang M. Targeting ERK, an Achilles' Heel of the MAPK pathway, in cancer therapy. Acta Pharm Sin B 2018; 8: 552-62.
13. Lee S, Rauch J, Kolch W. Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity. Int J Mol Sci 2020; 21: 1102. doi: 10.3390/ijms21031102.
14.Czirbesz K, Gorka E, Balatoni T, Panczel G, Melegh K, Kovacs P, et al. Efficacy of Vemurafenib Treatment in 43 Metastatic Melanoma Patients with BRAF Mutation. Single-Institute Retrospective Analysis, Early Real-Life Survival Data. Pathol Oncol Res 2019; 25: 45-50.
15.Takahashi A, Namikawa K, Nakano E, Yamazaki N. Real-world efficacy and safety data for dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation-positive advanced melanoma. J Dermatol 2020; 47: 257-64.
16.Trojaniello C, Festino L, Vanella V, Ascierto PA. Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations. Expert Rev Clin Pharmacol 2019; 12: 259-66.
17.Ascierto PA, McArthur GA, Dreno B, Atkinson V, Liszkay G, Di Giacomo AM, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol 2016; 17: 1248-60.
18.Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, et al. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol 2018; 36: 7-13.
19. Wang J, Zhao W, Guo H, Fang Y, Stockman SE, Bai S, et al. AKT isoform-specific expression and activation across cancer lineages. BMC cancer 2018; 18: 742.
20. Kumar CC, Madison V. AKT crystal structure and AKT-specific inhibitors. Oncogene 2005; 24: 7493-501.
21. Liao Y, Hung MC. Physiological regulation of Akt activity and stability. Am J Transl Res 2010; 2: 19-42.
22. Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer cell 2003; 4: 257-62.
23. Manning BD, Toker A. AKT/PKB Signaling: Navigating the Network. Cell 2017; 169: 381-405.
24. Kong D-x, Yamori T. ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor identified using the JFCR39 drug discovery system. Acta Pharmacologica Sinica 2010; 31: 1189-97.
25. Wendel HG, De Stanchina E, Fridman JS, Malina A, Ray S, Kogan S, et al. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature 2004; 428(6980): 332-7.
26. Chen X, Thakkar H, Tyan F, Gim S, Robinson H, Lee C, et al. Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer. Oncogene 2001; 20(42): 6073-83.
27. Bai D, Ueno L, Vogt PK. Akt-mediated regulation of NFB and the essentialness of NFB for the oncogenicity of PI3K and Akt. Int J Cancer 2009; 125(12): 2863-70.
28. Ogawara Y, Kishishita S, Obata T, Isazawa Y, Suzuki T, Tanaka K, et al. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem 2002; 277(24): 21843-50.
29. Ma YY, Wei SJ, Lin YC, Lung JC, Chang TC, Whang-Peng J, et al. PIK3CA as an oncogene in cervical cancer. Oncogene 2000; 19(23): 2739-44.
30. Hashimoto K, Mori N, Tamesa T, Okada T, Kawauchi S, Oga A, et al. Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH. Mod Pathol 2004; 17(6): 617-22.
31. Cheng JQ, Godwin AK, Bellacosa A, Taguchi T, Franke TF, Hamilton TC, et al. AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc Natl Acad Sci USA 1992; 89(19): 9267-71.
32. Miwa W, Yasuda J, Murakami Y, Yashima K, Sugano K, Sekine T, et al. Isolation of DNA Sequences Amplified at Chromosome 19q13.1–q13.2 Including theAKT2Locus in Human Pancreatic Cancer. Biochem Biophys Res Commun 1996; 225(3): 968-74.
33. Shariati M, Meric-Bernstam F. Targeting AKT for cancer therapy. Expert Opin Investig Drugs 2019; 28(11): 977-88.
34. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, et al. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 2002; 10(3): 457-68.
35. Cornu M, Albert V, Hall MN. mTOR in aging, metabolism, and cancer. Curr Opin Genet Dev 2013; 23(1): 53-62.
36. Zhao L, Vogt PK. Class I PI3K in oncogenic cellular transformation. Oncogene 2008; 27(41): 5486-96.
37. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307(5712): 1098-101.
38. Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease. Cell 2017; 168(6): 960-76.
39. Murugan AK. mTOR: Role in cancer, metastasis and drug resistance. Semin Cancer Biol 2019; 59: 92-111.
40. Russell RC, Fang C, Guan KL. An emerging role for TOR signaling in mammalian tissue and stem cell physiology. Development 2011; 138(16): 3343-56.
41. Pópulo H, Lopes JM, Soares P. The mTOR Signalling Pathway in Human Cancer. Int J Mol Sci 2012; 13(2): 1886-918.
42.Afshar M, Pascoe J, Whitmarsh S, James N, Porfiri E. Temsirolimus for patients with metastatic renal cell carcinoma: outcomes in patients receiving temsirolimus within a compassionate use program in a tertiary referral center. Drug Des Devel Ther 2015; 9: 13-9.
43.Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008; 372(9637): 449-56.
Downloads
Published
2020-07-22
How to Cite
1.
Klungsaeng S, Senggunprai L. Protein Serine-Threonine Kinases as Drug Target In Cancer Treatment. SRIMEDJ [Internet]. 2020 Jul. 22 [cited 2024 Dec. 24];35(4):488-95. Available from: https://li01.tci-thaijo.org/index.php/SRIMEDJ/article/view/245535
Issue
Section
Review Articles
