Understanding Cancer: Targeted Treatments
Cancers develop from multiple causes including genetic factors, infection, environmental toxin exposure and lifestyle factors such as tobacco use. Some are very slow growing while others grow and spread rapidly. No cure-all for cancer is likely in the near future. A strong immune system efficiently suppresses cellular and precancerous changes. With age and reduced immunity and sometimes for unknown reasons, abnormal cells grow and spread by direct extension to surrounding tissues, and metastasize throughout the body via blood and lymph. Each year treatments improve and many more of them are targeted at mutations and cell surface markers.
Two heritable disorders are mutations in the human genes that belong to a class of genes that are tumor suppressors, the BRCA1 and BRCA2 genes. The normal genes help stabilize DNA and prevent uncontrolled cell growth. Mutations block the stabilization and lead to early breast and ovarian cancer.
BRCA= BReast CAncer Susceptibility gene 1 and 2, affect both men and women. Men who carry this gene are also at risk for breast, and possibly pancreatic, testicular and early prostate cancer.
Other harmful mutations in the BRCA 2 gene increase risk of many other cancers including melanoma skin cancer.
Knowing you carry the BRCA gene can allow you to make decisions before the cancer develops. In women without the abnormal gene, the lifetime risk of developing breast cancer is 12% or 120/1000. In women with the harmful BRCA1 or BRCA2 mutation, they have a 60% chance or 600/1000, of developing the cancers. Many affected women make the decision to have both breasts and ovaries removed before cancer develops. This may sound drastic, but it is life saving.
An example of targeted treatment based on cell surface receptors is the Human Epidermal Growth Factor Receptor 2 (HER2) an abnormal protein found on breast cancer cells. The abnormal cancerous cell growth is triggered by an excess of HER2 due to a gene mutation and is found in other cancers, not just breast. This form of breast cancer tends to be more aggressive than other types. It is also less responsive to hormonal treatment.
Luckily there are two very specific drugs that target HER2, killing the abnormal cells but not the normal ones. These are Herceptin (Trastuzumab) and Tykerb (Lapatinib). Both may be used in combination with other chemo therapy drugs. They are not without side effects as both can cause heart toxicity and allergic reactions.
Other examples of innovations in the treatment of cancer patients are a vaccine that targets a particularly aggressive brain tumor (glioblastoma). This new treatment significantly prolongs life. Another is melanoma skin cancer. 40-60% of them contain a mutation that encodes BRAF gene. The BRAF mutation is associated with features of high risk aggressive melanoma. This gene makes a protein (B-Raf) which is involved with directing cell growth. Inhibitors have been developed to target the abnormality; one year ago Vemurafenib was released to treat late-stage melanoma.
Betty Kuffel, MD