Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Review Article

Targeting Notch Pathway in Cancer Diagnostics and Therapeutics: An Emerging Approach

Author(s): Chakresh Kumar Jain*, Shreya Bhargava, Isha Jain and Srishti Varshney

Volume 17, Issue 3, 2022

Published on: 06 April, 2022

Page: [244 - 252] Pages: 9

DOI: 10.2174/1574892816666210607092350

Price: $65

Abstract

The Notch signaling pathway is an evolutionarily conserved pathway usually present in multicellular organisms, which plays a pivotal role in cell fate determination and proliferation. Due to this property, it is known to be highly oncogenic, especially in the dysregulated version of the Notch pathway, where apoptosis is inhibited and abnormal cell growth is supported. Notch receptors and ligand proteins play an essential role in cancers, such as myeloid leukemia, T-cell lymphoblastic leukemia, and organ-specific, i.e., breast, colon, pancreas, and skin cancers. Any type of cancer generates due to genetic defects, including epigenetic alterations and mutations. The researchers can use these alterations to find a promising diagnostic as well as therapeutic tool for cancer. The successful inhibition of the Notch pathway with the help of specific biomarkers or suppression of gene expression represents a new remedy in cancer research. This article focuses on the various remedies hidden within the Notch pathway's mechanism, primarily based on different patents published in recent years for assisting cancer diagnosis and succeeding treatment.

Keywords: Notch pathway, dysregulation, cancer stem cells, NICD, γ secretase, mRNA.

[1]
Venkatesh V, Nataraj R, Thangaraj GS, et al. Targeting notch signalling pathway of cancer stem cells. Stem Cell Investig 2018; 5: 5.
[http://dx.doi.org/10.21037/sci.2018.02.02] [PMID: 29682512]
[2]
Yamamoto S, Schulze K L, Bellen H J. Introduction to notch signaling.Methods Mol Biol. 2014; 1187: pp. 1-14.1-14.
[http://dx.doi.org/10.1007/978-1-4939-1139-4_1] [PMID: 25053477]
[3]
Kumar S, Srivastav RK, Wilkes DW, et al. Estrogen-dependent DLL1-mediated notch signaling promotes luminal breast cancer. Oncogene 2019; 38(12): 2092-107.
[http://dx.doi.org/10.1038/s41388-018-0562-z] [PMID: 30442981]
[4]
Liu J, Shen JX, Wen XF, Guo YX, Zhang GJ. Targeting notch degradation system provides promise for breast cancer therapeutics. Crit Rev Oncol Hematol 2016; 104: 21-9.
[http://dx.doi.org/10.1016/j.critrevonc.2016.05.010] [PMID: 27263934]
[5]
Chowdhury S, Sarkar RR. Exploring notch pathway to elucidate phenotypic plasticity and intra-tumor heterogeneity in gliomas. Sci Rep 2019; 9(1): 9488.
[http://dx.doi.org/10.1038/s41598-019-45892-8] [PMID: 31263189]
[6]
Andersson ER, Sandberg R, Lendahl U. Notch signaling: Simplicity in design, versatility in function. Development 2011; 138(17): 3593-612.
[http://dx.doi.org/10.1242/dev.063610] [PMID: 21828089]
[7]
Yamamoto S, Charng WL, Bellen HJ. Endocytosis and intracellular trafficking of notch and its ligands. Curr Top Dev Biol 2010; 92: 165-200.
[http://dx.doi.org/10.1016/S0070-2153(10)92005-X] [PMID: 20816395]
[8]
Saltarella I, Frassanito MA, Lamanuzzi A, et al. Homotypic and heterotypic activation of the notch pathway in multiple myeloma-enhanced angiogenesis: A novel therapeutic target? Neoplasia 2019; 21(1): 93-105.
[http://dx.doi.org/10.1016/j.neo.2018.10.011] [PMID: 30529074]
[9]
Gersey Z, Osiason AD, Bloom L, et al. Therapeutic targeting of the notch pathway in glioblastoma multiforme. World Neurosurg 2019; 131: 252-263.e2.
[http://dx.doi.org/10.1016/j.wneu.2019.07.180] [PMID: 31376551]
[10]
Schott AF, Landis MD, Dontu G, et al. Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors. Clin Cancer Res 2013; 19(6): 1512-24.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-3326] [PMID: 23340294]
[11]
Allam H, Aoki K, Benigno BB, et al. Glycomic analysis of membrane glycoproteins with bisecting glycosylation from ovarian cancer tissues reveals novel structures and functions. J Proteome Res 2015; 14(1): 434-46.
[http://dx.doi.org/10.1021/pr501174p] [PMID: 25437919]
[12]
Feldinger K, Generali D, Kramer-Marek G, et al. ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer. Oncotarget 2014; 5(16): 6633-46.
[http://dx.doi.org/10.18632/oncotarget.1955] [PMID: 24952873]
[13]
Rana NA, Haltiwanger RS. Fringe benefits: Functional and structural impacts of O-glycosylation on the extracellular domain of notch receptors. Curr Opin Struct Biol 2011; 21(5): 583-9.
[http://dx.doi.org/10.1016/j.sbi.2011.08.008] [PMID: 21924891]
[14]
Wang NJ, Sanborn Z, Arnett KL, et al. Loss-of-function mutations in notch receptors in cutaneous and lung squamous cell carcinoma. Proc Natl Acad Sci USA 2011; 108(43): 17761-6.
[http://dx.doi.org/10.1073/pnas.1114669108] [PMID: 22006338]
[15]
Baron M. An overview of the notch signalling pathway. Semin Cell Dev Biol 2003; 14(2): 113-9.
[http://dx.doi.org/10.1016/s1084-9521(02)00179-9] [PMID: 12651094]
[16]
Goriki A, Seiler R, Wyatt AW, et al. Unravelling disparate roles of NOTCH in bladder cancer. Nat Rev Urol 2018; 15(6): 345-57.
[http://dx.doi.org/10.1038/s41585-018-0005-1] [PMID: 29643502]
[17]
Fortini ME. Notch signaling: the core pathway and its posttranslational regulation. Dev Cell 2009; 16(5): 633-47.
[http://dx.doi.org/10.1016/j.devcel.2009.03.010] [PMID: 19460341]
[18]
Rahman MT, Nakayama K, Rahman M, et al. Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer. Am J Clin Pathol 2012; 138(4): 535-44.
[http://dx.doi.org/10.1309/AJCPKDLRQ8F3EWNS] [PMID: 23010708]
[19]
He DE, Bai JW, Liu J, Du CW, Huang WH, Zhang GJ. Clinicopathological characteristics and prognosis of breast cancer patients with type 2 diabetes mellitus. Mol Clin Oncol 2015; 3(3): 607-12.
[http://dx.doi.org/10.3892/mco.2015.522] [PMID: 26137275]
[20]
Pierfelice T, Alberi L, Gaiano N. Notch in the vertebrate nervous system: An old dog with new tricks. Neuron 2011; 69(5): 840-55.
[http://dx.doi.org/10.1016/j.neuron.2011.02.031] [PMID: 21382546]
[21]
Louvi A, Artavanis-Tsakonas S. Notch and disease: A growing field. Semin Cell Dev Biol 2012; 23(4): 473-80.
[http://dx.doi.org/10.1016/j.semcdb.2012.02.005] [PMID: 22373641]
[22]
Lieber T, Kidd S, Struhl G. DSL-Notch signaling in the drosophila brain in response to olfactory stimulation. Neuron 2011; 69(3): 468-81.
[http://dx.doi.org/10.1016/j.neuron.2010.12.015] [PMID: 21315258]
[23]
Ortica S, Tarantino N, Aulner N, Israël A, Gupta-Rossi N. The 4 Notch receptors play distinct and antagonistic roles in the proliferation and hepatocytic differentiation of liver progenitors. FASEB J 2014; 28(2): 603-14.
[http://dx.doi.org/10.1096/fj.13-235903] [PMID: 24145721]
[24]
Chang WH, Lai AG. Aberrations in notch-hedgehog signalling reveal cancer stem cells harbouring conserved oncogenic properties associated with hypoxia and immunoevasion. Br J Cancer 2019; 121(8): 666-78.
[http://dx.doi.org/10.1038/s41416-019-0572-9] [PMID: 31523055]
[25]
Kumar R, Juillerat-Jeanneret L, Golshayan D. Notch antagonists: potential modulators of cancer and inflammatory diseases. J Med Chem 2016; 59(17): 7719-37.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01516] [PMID: 27045975]
[26]
Nagamatsu I, Onishi H, Matsushita S, et al. NOTCH4 is a potential therapeutic target for triple-negative breast cancer. Anticancer Res 2014; 34(1): 69-80.
[PMID: 24403446]
[27]
Luiken S, Fraas A, Bieg M, et al. NOTCH target gene HES5 mediates oncogenic and tumor suppressive functions in hepatocarcinogenesis. Oncogene 2020; 39(15): 3128-44.
[http://dx.doi.org/10.1038/s41388-020-1198-3] [PMID: 32055024]
[28]
Al-Maghrebi M, Renno WM. Genistein alleviates testicular ischemia and reperfusion injury-induced spermatogenic damage and oxidative stress by suppressing abnormal testicular matrix metalloproteinase system via the notch 2/jagged 1/Hes-1 and caspase-8 pathways. J Physiol Pharmacol 2016; 67(1): 129-37.
[PMID: 27010902]
[29]
Aifantis I, Trimarchi T. Methods and reagents for the diagnosis and treatment of acute leukemia. US20170035795A1, 2017.
[30]
Levy Y, Benkirane M, Yatim A. Method for screening a compound capable of inhibiting the notch1 transcriptional activity. US20150276760A1, 2015.
[31]
Sarkar RR, Chowdhury S. Identification of minimal combinations of oncoproteins in notch pathway to suppress human glioblastoma. US20160125127A1, 2016.
[32]
Hipskind PA, Stevenson GA. Notch pathway signaling inhibitor compounds. JP2018520157A, 2018.
[33]
West JW. Anti-jagged 1/jagged 2 cross-reactive antibodies, activatable anti-jagged antibodies and methods of use thereof. KR20150037857A, 2015.
[34]
Bernstein BE. Diagnostic and treatment methods in subjects having or at risk of developing resistance to cancer therapy. EP2861255B1, 2019.
[35]
Erik DF, Christian H, Siebel W. Compositions and methods for diagnosis and treatment of hepatic cancers. US10266602B2, 2019.
[36]
Stolpe AVD, Wilhelmus LHFMH, Verhaegh FJ. Determination of notch pathway activity using unique combination of target genes. US20190100790A1, 2019.
[37]
Hojin Y, Kim M, Yeob JI. Use of APE/Ref-1 and JAG1/Notch as a diagnostic marker of colon cancer. KR101514877B1, 2015.
[38]
Hoey TC. Methods of treating hematological malignancies with notch1 antibodies. EP2897643A1A1, 2015.
[39]
Mariano Anti-fibulin-3 antibodies and uses thereof. US201901177426A1, 2019.
[40]
Beckmann RP, Patel BK. Combination therapy with notch and cdk4/6 inhibitors for the treatment of cancer. EP3442529A1, 2019.
[41]
Alitalo K, Anisimov A, Yamamoto M. Biomarker for sensitivity to therapy with a notch inhibitor. US20130039930A1, 2013.
[42]
Clarke R. Breast Cancer Biomarker. US20160376659A1, 2016.
[43]
Spyros TA. Modulators of notch receptor signaling and methods of use thereof. WO2011140295A2, 2012.
[44]
Bender MH, Gao H, Patel BK. Combination therapy with notch and pd-1 or pd-l1 inhibitors. WO2017200969A1, 2017.
[45]
Kitajewski J. Human notch decoys. TW201329105A, 2013.
[46]
Desai Neil P. Method for treating pancreatic cancer. JP2016520289A, 2016.
[47]
Kenneth GG. Anti-notch1 antibody. JP2014503205A, 2014.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy