Systematic Identification of Cancer Pathways and Potential Drugs for Intervention Through Multi-omics Analysis

Overview

Journal Pharmacogenomics J

Specialties Genetics
Molecular Biology
Pharmacology

Date 2025 Feb 19

PMID 39971899

Authors

Tuan Xu

Deborah K Ngan

Wei Zheng

Ruili Huang

Affiliations

Soon will be listed here.

Abstract

The pathogenesis of cancer is complicated, and different types of cancer often exhibit different gene mutations resulting in different omics profiles. The purpose of this study was to systematically identify cancer-specific biological pathways and potential cancer-targeting drugs. We collectively analyzed the transcriptomics and proteomics data from 16 common types of human cancer to study the mechanism of carcinogenesis and seek potential treatment. Statistical approaches were applied to identify significant molecular targets and pathways related to each cancer type. Potential anti-cancer drugs were subsequently retrieved that can target these pathways. The number of significant pathways linked to each cancer type ranged from four (stomach cancer) to 112 (acute myeloid leukemia), and the number of therapeutic drugs that can target these cancer related pathways, ranged from one (ovarian cancer) to 97 (acute myeloid leukemia and non-small-cell lung carcinoma). As a validation of our method, some of these drugs are FDA approved therapies for their corresponding cancer type. Our findings provide a rich source of testable hypotheses that can be applied to deconvolute the complex underlying mechanisms of human cancer and used to prioritize and repurpose drugs as anti-cancer therapies.

References

Ghandi M, Huang F, Jane-Valbuena J, Kryukov G, Lo C, McDonald 3rd E . Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature. 2019; 569(7757):503-508. PMC: 6697103. DOI: 10.1038/s41586-019-1186-3. View

Carvalho R, Matos do Canto L, Cury S, Hansen T, Jensen L, Rogatto S . Drug Repositioning Based on the Reversal of Gene Expression Signatures Identifies as a Therapeutic Target for Rectal Cancer. Cancers (Basel). 2021; 13(21). PMC: 8583090. DOI: 10.3390/cancers13215492. View

Giandomenico V, Cui T, Grimelius L, Oberg K, Pelosi G, Tsolakis A . Olfactory receptor 51E1 as a novel target for diagnosis in somatostatin receptor-negative lung carcinoids. J Mol Endocrinol. 2013; 51(3):277-86. DOI: 10.1530/JME-13-0144. View

Rinaldetti S, Zhou Q, Abbott J, de Jong F, Esquer H, Costello J . High-Content Drug Discovery Targeting Molecular Bladder Cancer Subtypes. Int J Mol Sci. 2022; 23(18). PMC: 9506379. DOI: 10.3390/ijms231810605. View

Selos Guerra F, Oliveira R, Fraga C, Mermelstein C, Fernandes P . ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells. Sci Rep. 2017; 7(1):13723. PMC: 5651822. DOI: 10.1038/s41598-017-14216-z. View

Shao M, Jiang L, Meng Z, Xu J . Computational Drug Repurposing Based on a Recommendation System and Drug-Drug Functional Pathway Similarity. Molecules. 2022; 27(4). PMC: 8878172. DOI: 10.3390/molecules27041404. View

Herceg Z, Vaissiere T . Epigenetic mechanisms and cancer: an interface between the environment and the genome. Epigenetics. 2011; 6(7):804-19. DOI: 10.4161/epi.6.7.16262. View

Heo Y, Hwa C, Lee G, Park J, An J . Integrative Multi-Omics Approaches in Cancer Research: From Biological Networks to Clinical Subtypes. Mol Cells. 2021; 44(7):433-443. PMC: 8334347. DOI: 10.14348/molcells.2021.0042. View

Deng M, Peng L, Li J, Liu X, Xia X, Li G . PPP1R14B Is a Prognostic and Immunological Biomarker in Pan-Cancer. Front Genet. 2021; 12:763561. PMC: 8631915. DOI: 10.3389/fgene.2021.763561. View

10.

Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin A, Kim S . The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012; 483(7391):603-7. PMC: 3320027. DOI: 10.1038/nature11003. View

11.

Abe H, Kamai T, Hayashi K, Anzai N, Shirataki H, Mizuno T . The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells. BMC Cancer. 2014; 14:412. PMC: 4081468. DOI: 10.1186/1471-2407-14-412. View

12.

Zhu D, Huang H, Pinkas D, Luo J, Ganguly D, Fox A . 2-Amino-2,3-dihydro-1-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors: Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy. J Med Chem. 2019; 62(16):7431-7444. PMC: 6985936. DOI: 10.1021/acs.jmedchem.9b00365. View

13.

Wu J, Liao X, Yu B, Su B . Dasatinib inhibits primary melanoma cell proliferation through morphology-dependent disruption of Src-ERK signaling. Oncol Lett. 2013; 5(2):527-532. PMC: 3573147. DOI: 10.3892/ol.2012.1066. View

14.

Rupniewska E, Roy R, Mauri F, Liu X, Kaliszczak M, Bellezza G . Targeting autophagy sensitises lung cancer cells to Src family kinase inhibitors. Oncotarget. 2018; 9(44):27346-27362. PMC: 6007948. DOI: 10.18632/oncotarget.25213. View

15.

Tammen S, Friso S, Choi S . Epigenetics: the link between nature and nurture. Mol Aspects Med. 2012; 34(4):753-64. PMC: 3515707. DOI: 10.1016/j.mam.2012.07.018. View

16.

Guo S, Li B, Xu X, Wang W, Wang S, Lv T . Construction of a 14-lncRNA risk score system predicting survival of children with acute myelocytic leukemia. Exp Ther Med. 2020; 20(2):1521-1531. PMC: 7388210. DOI: 10.3892/etm.2020.8846. View

17.

Bar-Shavit R, Maoz M, Kancharla A, Nag J, Agranovich D, Grisaru-Granovsky S . G Protein-Coupled Receptors in Cancer. Int J Mol Sci. 2016; 17(8). PMC: 5000717. DOI: 10.3390/ijms17081320. View

18.

Jaiswal A, Gautam P, Pietila E, Timonen S, Nordstrom N, Akimov Y . Multi-modal meta-analysis of cancer cell line omics profiles identifies ECHDC1 as a novel breast tumor suppressor. Mol Syst Biol. 2021; 17(3):e9526. PMC: 7983037. DOI: 10.15252/msb.20209526. View

19.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

20.

Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M . KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 2009; 38(Database issue):D355-60. PMC: 2808910. DOI: 10.1093/nar/gkp896. View