Epigenetic Changes and Cancer Treatment

Epigenetic Changes in Gene Expression

• Many protein and DNA modifications are potentially reversible.
• Inhibitors of DNA methyltransferases (DNMTs) include 5-azadeoxycytidine and decitabine.
• Inhibitors of histone deacetylases (HDACs) include valproic acid and vorinostat.
• These agents have been used to treat certain types of leukemias and lymphomas.

Tumor Angiogenesis

• Tumor cells need an adequate blood supply to survive.
• Tumor cells and surrounding cells secrete angiogenic factors to stimulate new blood vessel growth.
• Hypoxia induces HIF-1, which increases levels of vascular endothelial growth factor (VEGF).
• VEGF proteins interact with specific tyrosine kinase receptors on endothelial and lymphatic cells.

MicroRNAs in Cancer

• Oncogenic microRNAs include miR-17-92, miR-21, and miR-155.
• Tumor suppression microRNAs include let-7, miR-34, miR-15, and miR-16.
• MicroRNAs influence extrinsic factors that modulate tumors, such as interactions with the immune system and stromal cells.
• MicroRNAs are being investigated as biomarkers for cancer diagnosis, prognosis, and classification.
• MicroRNAs hold promise in therapy, where oligonucleotides are used to enhance expression of tumor suppressor miRNAs or antisense oligonucleotides are used to counter the action of oncogenic miRNAs.

Development of Colorectal Cancers

• Multistep genetic changes are associated with the development of colorectal cancers.
• Mutations in the APC gene initiate the formation of adenomas.
• A sequence of mutations in oncogenes and tumor suppressor genes can result in further progression to large adenomas and cancer.
• Patients with familial adenomatous polyposis (FAP) inherit mutations in the APC gene and develop numerous dysplastic aberrant crypt foci (ACF).
• Tumors from patients with hereditary nonpolyposis colon cancer (HNPCC) go through a similar series of mutations.

Growth Factors and Cancer Development

• Growth factors produce their effects by interacting with specific receptors on cell surfaces.
• Growth factors initiate various signaling events.
• Abnormalities of growth factors and their receptors play a major role in cancer development.
• Oncogenes involved in cancer development include K-RAS, BRAF, and PI3KCA.

Learn about the role of epigenetic changes in gene expression and cancer treatment. Discover how inhibitors of DNA methyltransferases and histone deacetylases can be used to treat certain types of leukemia. Test your knowledge on the reversible nature of these modifications.