Kinase inhibitors have played an increasingly prominent role in the treatment of cancer and other diseases. Currently, more than 25 oncology drugs that target kinases have been approved, and numerous additional therapeutics are in various stages of clinical evaluation. In this Review, we provide an in-depth analysis of activation mechanisms for kinases in cancer, highlight recent successes in drug discovery, and demonstrate the clinical impact of selective kinase inhibitors. We also describe the substantial progress that has been made in designing next-generation inhibitors to circumvent on-target resistance mechanisms, as well as ongoing strategies for combining kinase inhibitors in the clinic. Last, there are numerous prospects for the discovery of novel kinase targets, and we explore cancer immunotherapy as a new and promising research area for studying kinase biology.
Stefan Gross, Rami Rahal, Nicolas Stransky, Christoph Lengauer, Klaus P. Hoeflich
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Kidney toxicity of the BRAF-kinase inhibitor vemurafenib is driven by off-target ferrochelatase inhibition
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Ubiquitination of Nonhistone Proteins in Cancer Development and Treatment
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Frontiers in Oncology | 2021 |
ONC212 is a Novel Mitocan Acting Synergistically with Glycolysis Inhibition in Pancreatic Cancer
I Ferrarini, A Louie, L Zhou, WS El-Deiry |
Molecular cancer therapeutics | 2021 |
Inflammatory conversion of quiescent osteoblasts by metastatic breast cancer cells through pERK1/2 aggravates cancer-induced bone destruction
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Bone Research | 2021 |
Development of cell‐based high throughput luminescence assay for drug discovery in inhibiting OCT4/DNA‐PKcs and OCT4–MK2 interactions
IS Mohiuddin, SJ Wei, IH Yang, GM Martinez, S Yang, EJ Cho, KN Dalby, MH Kang |
Biotechnology and Bioengineering | 2021 |
Targeted mass-spectrometry-based assays enable multiplex quantification of receptor tyrosine kinase, MAP kinase, and AKT signaling
JR Whiteaker, K Sharma, MA Hoffman, E Kuhn, L Zhao, AR Cocco, RM Schoenherr, JJ Kennedy, U Voytovich, C Lin, B Fang, K Bowers, G Whiteley, S Colantonio, W Bocik, R Roberts, T Hiltke, E Boja, H Rodriguez, F McCormick, M Holderfield, SA Carr, JM Koomen, AG Paulovich |
2021 | |
Targeting Protein Kinases in Blood Cancer: Focusing on CK1α and CK2
Z Spinello, A Fregnani, LQ Tubi, L Trentin, F Piazza, S Manni |
International journal of molecular sciences | 2021 |
Copy number aberrations drive kinase rewiring, leading to genetic vulnerabilities in cancer
D Memon, MB Gill, EK Papachristou, D Ochoa, CS DSantos, ML Miller, P Beltrao |
Cell Reports | 2021 |
Bruton’s Tyrosine Kinase Targeting in Multiple Myeloma
MV Suskil, KN Sultana, WO Elbezanti, OS Al-Odat, R Chitren, AK Tiwari, KB Challagundla, SK Srivastava, SC Jonnalagadda, T Budak-Alpdogan, MK Pandey |
International journal of molecular sciences | 2021 |
Heterogeneous Off-Target Effects of Ultra-Low Dose Dimethyl Sulfoxide (DMSO) on Targetable Signaling Events in Lung Cancer In Vitro Models
E Baldelli, M Subramanian, AM Alsubaie, G Oldaker, M Emelianenko, EE Gazzah, S Baglivo, KA Hodge, F Bianconi, V Ludovini, L Crino, EF Petricoin, M Pierobon |
International journal of molecular sciences | 2021 |
Human papillomavirus E6 and E7: What remains?
A Vats, O Trejo-Cerro, M Thomas, L Banks |
2021 | |
Excipient-Free Pure Drug Nanoparticles Fabricated by Microfluidic Hydrodynamic Focusing
RS Arzi, A Kay, Y Raychman, A Sosnik |
Pharmaceutics | 2021 |
How Far Are We from the Rapid Prediction of Drug Resistance Arising Due to Kinase Mutations?
M Erguven, T Karakulak, MK Diril, E Karaca |
ACS Omega | 2021 |
A mechanism for localized dynamics-driven activation in Bruton's tyrosine kinase
S Qiu, Y Liu, Q Li |
Royal Society Open Science | 2021 |
Association of Combination of Conformation-Specific KIT Inhibitors With Clinical Benefit in Patients With Refractory Gastrointestinal Stromal Tumors: A Phase 1b/2a Nonrandomized Clinical Trial
AJ Wagner, PL Severson, AF Shields, A Patnaik, R Chugh, G Tinoco, G Wu, M Nespi, J Lin, Y Zhang, T Ewing, G Habets, EA Burton, B Matusow, J Tsai, G Tsang, R Shellooe, H Carias, K Chan, H Rezaei, L Sanftner, A Marimuthu, W Spevak, PN Ibrahim, K Inokuchi, O Alcantar, G Michelson, AC Tsiatis, C Zhang, G Bollag, JC Trent, WD Tap |
JAMA Oncology | 2021 |
Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3–amplified lung adenocarcinoma cells
L Shi, X Tan, X Liu, J Yu, N Bota-Rabassedas, Y Niu, J Luo, , C Zong, CJ Creighton, JS Glenn, J Wang, JM Kurie |
Proceedings of the National Academy of Sciences | 2021 |
Synthesis and Biological Evaluation of (S)-2-(Substituted arylmethyl)-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide Analogs and Their Synergistic Effect against PTEN-Deficient MDA-MB-468 Cells
YM Kwon, SH Kim, YS Jung, JH Kwak |
Pharmaceuticals (Basel, Switzerland) | 2021 |
Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction
S Giacosa, C Pillet, I Séraudie, L Guyon, Y Wallez, C Roelants, C Battail, B Evrard, F Chalmel, C Barette, E Soleilhac, MO Fauvarque, Q Franquet, C Sarrazin, N Peilleron, G Fiard, JA Long, JL Descotes, C Cochet, O Filhol |
Cancers | 2021 |
Fasting-Induced Upregulation of MKP-1 Modulates the Hepatic Response to Feeding
J Sellers, A Brooks, S Fernando, G Westenberger, S Junkins, S Smith, K Min, A Lawan |
Nutrients | 2021 |
Mechanisms of Pharmaceutical Therapy and Drug Resistance in Esophageal Cancer
C Mao, X Zeng, C Zhang, Y Yang, X Xiao, S Luan, Y Zhang, Y Yuan |
Frontiers in Cell and Developmental Biology | 2021 |
Inhibitors, PROTACs and Molecular Glues as Diverse Therapeutic Modalities to Target Cyclin-Dependent Kinase
S Rana, JR Mallareddy, S Singh, L Boghean, A Natarajan |
Cancers | 2021 |
Kinase Inhibitors’ Effects on Innate Immunity in Solid Cancers
C Peng, K Rabold, WJ Mulder, M Jaeger, RT Netea-Maier |
Cancers | 2021 |
ChiTaH: a fast and accurate tool for identifying known human chimeric sequences from high-throughput sequencing data
R Detroja, A Gorohovski, O Giwa, G Baum, M Frenkel-Morgenstern |
2021 | |
CSNK2 in cancer: pathophysiology and translational applications
SW Strum, L Gyenis, DW Litchfield |
British Journal of Cancer | 2021 |
Screening and Identification of Lujo Virus Inhibitors Using a Recombinant Reporter Virus Platform
SR Welch, JR Spengler, SC Genzer, P Chatterjee, M Flint, É Bergeron, JM Montgomery, ST Nichol, CG Albariño, CF Spiropoulou |
Viruses | 2021 |
Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication
G Garcia, A Sharma, A Ramaiah, C Sen, A Purkayastha, DB Kohn, MS Parcells, S Beck, H Kim, MA Bakowski, MG Kirkpatrick, L Riva, KC Wolff, B Han, C Yuen, D Ulmert, PK Purbey, P Scumpia, N Beutler, TF Rogers, AK Chatterjee, G Gabriel, R Bartenschlager, B Gomperts, CN Svendsen, UA Betz, RD Damoiseaux, V Arumugaswami |
Cell Reports | 2021 |
Short loop functional commonality identified in leukaemia proteome highlights crucial protein sub-networks
SS Chung, JC Ng, A Laddach, NS Thomas, F Fraternali |
2021 | |
Passive Diffusion vs Active pH-Dependent Encapsulation of Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into Folate-Targeted Ferritin Delivery System
Z Skubalova, S Rex, M Sukupova, M Zahalka, P Skladal, J Pribyl, H Michalkova, A Weerasekera, V Adam, Z Heger |
International Journal of Nanomedicine | 2021 |
Synthesis of illudalic acid and analogous phosphatase inhibitors
H Fulo, N Rueb, R Gaston, P Batsomboon, K Ahmed, A Barrios, G Dudley |
Organic & Biomolecular Chemistry | 2021 |
Inhibition of the CDK9‒cyclin T1 protein‒protein interaction as a new approach against triple-negative breast cancer
S Cheng, Y Qu, J Wu, G Yang, H Liu, W Wang, Q Huang, F Chen, G Li, C Wong, V Wong, D Ma, C Leung |
Acta pharmaceutica Sinica. B | 2021 |
Repurposing existing therapeutics, its importance in oncology drug development: Kinases as a potential target.
Islam S, Wang S, Bowden N, Martin J, Head R |
British Journal of Clinical Pharmacology | 2021 |