Targeted Drug Therapy
Targeted drug therapy uses drugs that take advantage of particular cellular pathways that differ between cancer cells and normal cells.
By targeting the differences that allow tumor cells to grow rapidly, this class of drugs can slow or block the growth of tumors by interfering with molecules or cellular processes that are unique to tumors.
Targeted drug therapy is increasingly used to treat brain tumors. It may be used alone or in combination with chemotherapy, and/or radiation therapy.
Unlike standard chemotherapy drugs, which typically target dividing cells and cannot distinguish between healthy or cancerous cells, targeted drug therapy interferes with specific molecular pathways that are altered in cancer cells. This means that these drugs usually do not have the same side effects as those seen with chemotherapy.
While research is ongoing to identify suitable targets for specific cancers, there are several basic strategies for developing a targeted drug therapy. Targeted drug therapies that are currently approved for brain tumors include the following:
Angiogenesis is the growth of new blood vessels, a critical step during the growth of aggressive brain tumors. Brain tumors must have a suitable blood supply to deliver the necessary oxygen and nutrients that tumor cells need for continued growth. Angiogenesis inhibitors (or anti-angiogenic drugs) can slow tumor growth by interfering with blood vessel formation and growth.
For example, bevacizumab (also called Avastin or MVASI) is an anti-angiogenic drug that slows tumor growth, and is currently approved for use in recurrent glioblastoma.
Signal transduction is the process through which cells respond to cues in the environment. For example, certain molecules can bind to proteins on the surface of a cell, causing a chain reaction of biochemical events (through a signaling pathway) that can affect whether a cell grows and divides. By interfering with components of specific signaling pathways, signal transduction inhibitors can block cellular processes that are critical for tumor growth and survival.
For example, everolimus (also called Afinitor) is a signal transduction inhibitor that blocks mTOR, a protein involved in cell growth, proliferation, and survival. This drug is currently approved for use in adults and children with subependymal giant cell astrocytoma, specifically those with a diagnosis of tuberous sclerosis and a tumor(s) that is inoperable.
In low-grade pediatric gliomas, alterations in a gene called BRAF are often responsible for driving tumor cell proliferation and survival via abnormal signals from the MAPK/ERK pathway. The combination of dabrafenib (also known as Tafinlar) and trametinib (also known as Mekinist) is approved for children over the age of 1 to treat low-grade gliomas with a BRAF mutation. Tovarafenib (also known as Ojemda) is approved for children 6 months and older to treat low-grade gliomas with changes in the BRAF gene, including fusions, rearrangements, or a mutation.
IDH is a protein that plays an important role in cell metabolism, or how they process carbohydrates, proteins, and fats into energy. It has two different forms (IDH1 and IDH2) that serve this identical function. As part of the citric acid cycle (also known as the Krebs cycle), both forms are responsible for converting the isocitrate metabolite into alpha ketoglutarate. When the IDH gene is mutated, the alpha ketoglutarate instead gets converted into 2-hydroxyglutarate (2-HG), which scientists think may cause tumor growth. Therefore, drugs that block the mutated IDH proteins from making the harmful byproduct of 2-HG may slow tumor growth and delay the timing of subsequent, more intensive treatments.
Vorasidenib (also called Voranigo) specifically blocks the mutated versions of both the IDH1 and IDH2 proteins. The drug is approved for use in adults and children over the age 12 to treat grade 2 oligodendrogliomas or astrocytomas that have mutations in IDH1 or IDH2.
Additional strategies for targeted drug therapies have been successful in treating other cancers, and ongoing research is being done to identify and test targeted drug therapies for brain tumors.
This content was reviewed by UCSF neuro-oncologist Jennie Taylor, MD, MPH.