Exploring New Frontiers in Cancer Treatment
by Kim Thiboldeaux and Mitch Golant, PhD
Surgery, chemotherapy, and radiation remain the standard ways to treat cancer, but we look forward to the day when cancer treatment can be tailored to each individual – and a day when the word “cure” is more a part of our vocabulary. While cancer treatment is not yet at that point, scientists have made great advances in medical research, bringing us much closer to the goal of personalizing medicine.
Over the past decade, great advances have been made in understanding the differences between cancer cells and normal cells. Because of this, researchers have been able to make remarkable progress in developing drugs that can target cancer cells without affecting healthy cells (often called targeted therapies and biomarker screening for specific elements of cancer cells that can be used to individualize treatment.
Tailoring, or personalizing, medicine involves new tests and techniques that help doctors understand more about each person’s cancer at the cellular level. When a physician knows more about a person’s actual cancer cells, he or she can select drugs and treatments that will more likely lead to a successful outcome with fewer harmful side effects. This is the future: a future where doctors can know more about what’s happening in your body and where cancer treatments will be more effective at finding and correcting problems.
Targeting Cancer Drugs to Cancer
Unlike traditional therapies, new cancer treatments recognize cellular characteristics that distinguish cancer cells from normal cells. Doctors can use screening tests to identify the cancer cells in your body that would be susceptible to targeted treatments. The two main types of targeted therapies currently available are monoclonal antibodies and small-molecule inhibitors.
Unlike traditional therapies, new cancer treatments recognize cellular characteristics that distinguish cancer cells from normal cells.
Therapeutic Monoclonal Antibodies
Monoclonal antibodies (MABs or MoAbs) are antibodies created in the laboratory that target specific proteins (antigens) on the surface of cancer cells. The generic drug names of monoclonal antibodies often end in “mab.”
When a monoclonal antibody binds with the protein antigen on cancer cells, it acts like a key that fits only one lock on the cell surface. Once a monoclonal antibody in a cancer drug locks into the cell’s surface, one of several actions can occur to kill cancer cells:
• The monoclonal antibody can block signals to the core of the cancer cell (nucleus), so that it can no longer grow or repair itself.
• The monoclonal antibody can attract the body’s immune system to destroy the cancer cell or start the signal for cell death.
Scientists have discovered that monoclonal antibodies can also be used as a delivery system to take other treatment agents to cancer cells directly. For example, monoclonal antibodies are used to deliver radiation, chemotherapy, cytokines (immune system messengers), DNA molecules, and small-molecule inhibitors to selectively targeted cells. Once the monoclonal antibody carries the other drug directly to the cancer, the drug can work to destroy the abnormal cells while leaving healthy cells unaffected. To date, all versions of monoclonal antibody therapies are similar in their effectiveness and safety. Some people experience allergic reactions to this treatment, but that is treatable. Mostly, the potential benefits for cancer treatment are promising.
Dr. Mitch Golant
Small-molecule inhibitors (sometimes called enzyme inhibitors) interfere with signals inside the cell to stop those signals from making the cancer cells grow and divide. The generic drug names of smallmolecule inhibitors often end in “inib.”
In cancer cells, there is often an abnormally high level of signals instructing tumor cells to grow and divide faster than normal. Small-molecule inhibitors block the actions of the enzyme-growth receptors and prevent cell-growth signals from reaching the nucleus of the cancer cells. In this way, they are able to prevent cancer cells from dividing.
“Targets” for Anti-Cancer Drugs
A good target for a cancer drug is one known to affect the growth and survival of cancer cells. There are many signaling pathways in cancer cells that promote cell division by activating a specific receptor on the cell wall. Scientists have begun to successfully develop drugs that block some of these pathways.
Two examples of targets that fall into this category belong to a family of protein receptors found on the surface of normal and cancer cells called human epidermal growth factor receptors (EGFRs). There are at least four members of this family of receptors: HERl, HER2, HER3, and HER4. Doctors sometimes refer to HERl as “EGFR” because this was the first receptor found. Later, other members of the HER family were found, which is why the numeric distinction was applied.
Continued research into better strategies for stimulating the body’s immune system to fight cancer is ongoing.
Scientists have found that many types of cancer cells have high levels of HERl (EGFR) or HER2. When abnormally high levels of these proteins are present on the cell surface, cells divide too rapidly, thus causing cancer tumors. Specific tests can measure whether abnormal levels of HERl (EGFR) or HER2 are present treated with anti-cancer drugs that block, or inhibit, HERl- or HER2-related tumor growth, including: Herceptin® (trastuzumab), a monoclonal antibody used against breast cancer; Tarcevar® (erlotinib), a small molecule drug used against non-small cell lung cancer or advanced pancreatic cancer; or Erbitux® (cetuximab), a monoclonal antibody used against colorectal cancer or certain types of head and neck cancer. These drugs target human epidermal growth factor receptors to stop the related cancer cells from dividing.
Another important target for anticancer therapies is the vascular endothelial growth factor (VEGF). VEGF is a protein that stimulates growth and is necessary for the production of the blood vessels in cancerous tumors. Without these vessels, tumors have difficulty growing because they are otherwise starved of nutrients. VEGF is produced naturally by the body but can also be produced in abnormal amounts by cancer cells. VEGF is an important biomarker for cancer diagnosis and treatment.
Antiangiogenesis agents are a class of drugs that target VEGF to starve cancerous tumors. Angiogenesis is the normal biologic process of developing new blood vessels that transport nutrients and oxygen to cells and organs. During the development and spread of cancer, this process works against the body because tumors use the same process to feed their growth. New blood vessels may “feed” cancer cells with oxygen and nutrients, allowing the bad cells to grow, move into nearby tissue, and spread to other parts of the body.
Scientists are determining ways to reverse or stop the process of angiogenesis. Selectively cutting off or “starving” the growth system of tumor cells is called antiangiogenesis. One example of a drug that falls into this category is Avastin® (bevacizumab), a monoclonal antibody used to treat metastatic colorectal cancer, metastatic non-small cell lung cancer, metastatic breast cancer, glioblastoma, and metastatic kidney cancer.
Targeted treatments may work better when they are used in combination with cell-killing agents such as radioactive isotopes, chemotherapy drugs, and toxins. These combinations allow the cell-killing drug or radioactivity to be delivered directly to the cancer cell, with the goal of sparing normal, healthy cells.
Stimulating the body’s immune system, also known as immunotherapy, has been studied by cancer researchers for many years. Because cancer cells are “insiders” and have a mechanism to help make them invisible to the body’s immune system, cancer cells can multiply into large tumors without triggering an effective immune response. Cancer vaccines are being developed to counter these tactics by tricking the immune system into recognizing the tumor and prompting the immune system to fight back.
Cancer vaccines have several proven and potential advantages over standard therapies.
♦ They are well tolerated, with few and fairly minor side effects. This is because they help the immune system distinguish if cells are tumor or normal cells, so that only harmful cells will be attacked. Standard therapy kills both tumor cells and healthy cells, causing unpleasant – and sometimes serious – side effects.
♦ They may produce longer remissions or prevent recurrence. Once the immune system is triggered to attack tumor cells, it might remain on alert longer to destroy them. With standard therapy, a few resistant tumor cells are often able to survive and cause a return of the disease.
♦ They may be effective even against metastatic disease – cancer that has spread beyond its initial site to other parts of the body. The immune system serves the entire body and can hunt down and destroy wandering tumor cells wherever they gather.
Many cancer vaccines are undergoing clinical trials to evaluate their effectiveness. In 2010, the first therapeutic cancer vaccine, called Provenge® (sipuleucel-T), was approved by the U.S. Food and Drug Administration for the treatment of prostate cancer. The promising research in this area is offering a great deal of hope for researchers and cancer survivors alike.
Recruiting the Immune System
Continued research into better strategies for stimulating the body’s immune system to fight cancer is ongoing. For example, one area of immunotherapy research is with the use of cytokines, which are considered “immune system messengers.” Some cytokines, which can be produced in the laboratory, can be given to people with cancer either to boost their own immune systems or to slow down the growth of the cancer.
Another immunotherapy research strategy involves adoptive immunotherapy, which genetically instructs a human immune cell to seek and kill cancer cells. Cells called T-cells are taken from an individual and modified; when they are returned to the individual, they recognize, target, and kill his or her own tumor cells. There is hope that research in this area will continue to unlock the mysteries of the immune system and cancer.
♦ ♦ ♦ ♦ ♦
Kim Thiboldeaux is president and CEO of the Cancer Support Community. Dr. Mitch Golant is a health psychologist and senior vice president of Research & Training for the Cancer Support Community.
Excerpted with permission from Reclaiming Your Life After Diagnosis: The Cancer Support Community Handbook, by Kim Thiboldeaux and Mitch Golant, PhD, copyright © 2012 by the Cancer Support Community. All rights reserved.
For a complete list of targeted therapies and discussion of anti-cancer drugs currently available in the United States, visit the National Cancer Institute website, cancer.gov.
This article was originally published in Coping® with Cancer magazine, September/October 2012.