Medicinal Chemistry and Biology of Cancer
- Pp. 350-377 (28)Robert E. Smith
Cancer is the rapid, unregulated and pathological growth (proliferation) of abnormal cells. Even when cancers occur in the same part of the body, they can be very different diseases. When tumors become malignant, their threat depends on their ability to modify surrounding cells to form new blood vessels (angiogenesis) and other supporting cells. The typical American diet that leads to obesity can make people more susceptible to cancer. The human papilloma virus, hepatitis B and T cell leukemia virus type 1 can cause cancer of the cervix, liver and leukocytes (leukemia). Tyrosine kinases regulate many cellular processes which can contribute to cancer development and progression. KRAS is the oncoprotein that is most commonly activated in human cancer. RAS is one of the most commonly mutated genes in human cancers. Oncogenes code for oncoproteins, which are upregulated in cancer. Another important oncogene is PI3K, which codes for the enzyme PI3K (phosphoinositide 3-kinase). The enzyme PTEN (phosphatase and tensin homolog) catalyzes the opposite reaction, so it is a tumor suppressor and the gene coding for it is downregulated in cancer. Human epidermal growth factor (hEGF, or HER), vascular endothelial growth factor, or VEGF, and the PI3K/AKT/mTOR (mammalian target of rapamycin) survival pathway are all important therapeutic target in many cancers. Cancer stem cells could be good targets for new drugs that will prevent the recurrence and metastasis of tumors. Also, induced pluripotent stem cells could be used to screen drugs to see if they will be effective in treating each individual patient.