Targeting cancer with small molecule kinase inhibitors

By Jianming Zhang, Priscilla L. Yang, Nathanael S. Gray. Nature Reviews. Cancer, 2009

2,565 citations recorded by the source corpus.

Deregulation of kinase activity has emerged as a major mechanism by which cancer cells evade normal physiological constraints on growth and survival. To date, 11 kinase inhibitors have received US Food and Drug Administration approval as cancer treatments, and there are considerable efforts to develop selective small molecule inhibitors for a host of other kinases that are implicated in cancer and other diseases. Herein we discuss the current challenges in the field, such as designing selective inhibitors and developing strategies to overcome resistance mutations. This Review provides a broad overview of some of the approaches currently used to discover and characterize new kinase inhibitors.

Subfields: Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/8bef75e9179720c1f5054c91e9c799b00bf3af34

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Citations in the corpus

Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. (2014, background): “Many of the kinase inhibitors are sensitive to plasma drug concentration to maintain on-target activity and molecular pathways can reactivate as plasma concentrations decline [20].”
The cell cycle and cancer (2012, background): “Hence the cancer circumnavigates the ‘specific’ target and eludes the targeted therapy [15,30].”
Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer (2009, background): “For example, so-called 'gatekeeper' mutations may occur after targeted protein kinase therapy (reviewed in Ref”
ERK1/2 MAP kinases: structure, function, and regulation. (2012, background): “Most small-molecule inhibitors of rotein kinases that compete with ATP binding also make hydrogen onds with the backbone residues of the hinge region [67].”
Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution (2010, background): “A good example is the set of all heterocycles that mimic how adenine binds to the hinge region of kinases [11].”
Intratumor heterogeneity: the Rosetta stone of therapy resistance (2020, background): “Small molecule inhibitors, directed against abnormal signaling of mutated kinases, are commonly used as frontline therapies for cancers with druggable driver lesions, such as EGFR and ALK in EGFR and ALK mutant lung cancers, or BRAF in melanoma (Zhang et al., 2009).”
The ErbB/HER family of protein-tyrosine kinases and cancer. (2014, background): “Most smallmolecule inhibitors of protein kinases that compete with ATP binding also make hydrogen bonds with the backbone residues of the connecting hinge [62].”
Kinase-targeted cancer therapies: progress, challenges and future directions (2018, background): “Many previously approved kinase inhibitors are being tested in clinical trials against BRAF and cyclin-dependent kinases 4/6 mutations [20, 99].”
Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. (2014, background): “When deregulated, it is also critically involved in disease processes, notably in cancer, where protein kinases are now the major class of drug targets (Rix and Superti-Furga, 2009; Zhang et al., 2009).”