» Articles » PMID: 35798235

Targeting Micro-environmental Pathways by PROTACs As a Therapeutic Strategy

Overview
Specialty Oncology
Date 2022 Jul 7
PMID 35798235
Authors
Affiliations
Soon will be listed here.
Abstract

Tumor microenvironment (TME) composes of multiple cell types and non-cellular components, which supports the proliferation, metastasis and immune surveillance evasion of tumor cells, as well as accounts for the resistance to therapies. Therefore, therapeutic strategies using small molecule inhibitors (SMIs) and antibodies to block potential targets in TME are practical for cancer treatment. Targeted protein degradation using PROteolysis-TArgeting Chimera (PROTAC) technic has several advantages over traditional SMIs and antibodies, including overcoming drug resistance. Thus many PROTACs are currently under development for cancer treatment. In this review, we summarize the recent progress of PROTAC development that target TME pathways and propose the potential direction of future PROTAC technique to advance as novel cancer treatment options.

Citing Articles

Deciphering the Prognostic and Therapeutic Significance of Cell Cycle Regulator CENPF: A Potential Biomarker of Prognosis and Immune Microenvironment for Patients with Liposarcoma.

Chen J, Lian Y, Zhao B, Han J, Li X, Wu J Int J Mol Sci. 2023; 24(8).

PMID: 37108172 PMC: 10139200. DOI: 10.3390/ijms24087010.


Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy.

Li X, Zhao Z, Yu X, Xia Q, Zhou P, Wang S Exp Hematol Oncol. 2023; 12(1):34.

PMID: 36998063 PMC: 10061905. DOI: 10.1186/s40164-023-00394-2.


Targeted protein posttranslational modifications by chemically induced proximity for cancer therapy.

Peng Y, Liu J, Inuzuka H, Wei W J Biol Chem. 2023; 299(4):104572.

PMID: 36870680 PMC: 10050664. DOI: 10.1016/j.jbc.2023.104572.


Adriamycin-loaded exosome with anti-CD20 aptamers selectively suppresses human CD20+ melanoma stem cells.

Chen H, Jiang Y, Li X Skin Res Technol. 2023; 29(1):e13259.

PMID: 36704890 PMC: 9838758. DOI: 10.1111/srt.13259.

References
1.
Engelhardt H, Bose D, Petronczki M, Scharn D, Bader G, Baum A . Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors. J Med Chem. 2019; 62(22):10272-10293. DOI: 10.1021/acs.jmedchem.9b01169. View

2.
Sharma P, Hu-Lieskovan S, Wargo J, Ribas A . Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017; 168(4):707-723. PMC: 5391692. DOI: 10.1016/j.cell.2017.01.017. View

3.
Venton G, Perez-Alea M, Baier C, Fournet G, Quash G, Labiad Y . Aldehyde dehydrogenases inhibition eradicates leukemia stem cells while sparing normal progenitors. Blood Cancer J. 2016; 6(9):e469. PMC: 5056970. DOI: 10.1038/bcj.2016.78. View

4.
Donovan K, Ferguson F, Bushman J, Eleuteri N, Bhunia D, Ryu S . Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development. Cell. 2020; 183(6):1714-1731.e10. PMC: 10294644. DOI: 10.1016/j.cell.2020.10.038. View

5.
Piya S, Yang Y, Bhattacharya S, Sharma P, Ma H, Mu H . Targeting the NOTCH1-MYC-CD44 axis in leukemia-initiating cells in T-ALL. Leukemia. 2022; 36(5):1261-1273. PMC: 9061299. DOI: 10.1038/s41375-022-01516-1. View