Intracellular Signaling

Published on 04/03/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

Last modified 04/03/2015

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Chapter 2

Intracellular Signaling

Summary of Key Points

• Ligand binding and activation of cell surface and internal receptors triggers the activation and/or suppression of signaling cascades that regulate diverse cellular processes, including cell growth, proliferation, survival, and invasion, among others.

• Multiple nodes within these intracellular signaling networks are genetically and epigenetically altered in human cancers, leading to constitutive pathway activation or suppression.

• A subset of cancers are dependent on genomic alterations in oncogenes or tumor suppressor genes for their growth and survival, a phenomenon known as “oncogene addiction.”

• Drugs that selectively inhibit altered proteins that are critical for the maintenance of the transformed phenotype have shown unprecedented clinical activity in genetically defined subsets of cancers.

• Precision medicine is the use of genetic and epigenetic information to develop treatment regimens that target the driver oncogenes and tumor suppressors responsible for tumor progression in individual patients with cancer. Potential challenges to the application of this approach include the current inability to directly inhibit some oncogenic proteins (i.e., KRAS), the development of drug resistance, technical hurdles posed by limited tissue availability for genomic studies, and intratumoral and lesion-to-lesion genomic heterogeneity.