Editor’s note: Cancer Q&A is a monthly column in which health professionals from Baystate Regional Cancer Program, based in Springfield, address issues related to cancer in a question and answer format.
Q: What is cancer?
A: Cancer is a collection of diseases with a number of things in common.
For over 150 years we have defined cancer by what it looks like under the microscope and by where it begins in the body.
Taking a piece of cancer tissue and doing a microscopic examination shows that it is invading the surrounding tissue. Such invasion correlates with the ability of cancer cells to spread or metastasize to other parts of the body, potentially causing bone pain and fractures, as well as damage to other vital organs in the body. We have referred to cancers as being from the breast, colon, lung, prostate or other anatomic sites.
Things are different today. The laboratory research done over the past 50 years has led to a new way of looking at cancer. We have greater understanding of how cells work, both normal and cancerous, and have identified the pieces of the cell machinery that get broken and lead to cancer.
We are now starting to define cancer by molecular changes in the genes, what we refer to as the cell’s control center. There is a better understanding of the genomic alterations and how that causes the hallmarks of cancer, such as stimulation of blood vessel growth, which further allows the cancer to grow, and tissue invasion, damaging other parts of the body.
The hope is that this better molecular understanding will not only change our definitions of cancer, but allow new treatments to take advantage of the precise gene changes.
Q: What causes cancer?
A: Cancer develops as a result of a mutation in a gene. Genes are made of DNA and provide the code or message that allows the cell to make proteins and other important pieces of the cell machinery such as RNA (one of the three major biological macromolecules that are essential for all known forms of life along with DNA and proteins). When there is a mutation, there can be too much or too little of the protein made, or an abnormal protein can result. These changes can cause cells to become independent and have the hallmarks of cancer.
Mutations can occur with time as part of the wear and tear of the genes, so that cancer is much more common the older we get.
Or, mutations can occur from exposure to toxins, such as cigarette smoke or radiation from excessive sunlight. Time and toxins are the most common reasons for mutations.
Mutations can also occur in the germ line, meaning the genes we inherit from one of our parents. Germ line mutations are related to inherited risk such as with BRCA-related breast cancer. BRCA1and BRCA2 are human genes that, when working properly, prevent tumors from forming through proteins they produce that help maintain DNA function. In this situation, we don’t inherit the cancer but rather the abnormal gene that can lead to a higher chance of developing cancer.
For many of these kinds of cancers, there is a pattern of cancer in the family and cancers tend to occur at younger ages.
Q: How is cancer treated?
A: The major of treatments for cancer have been surgery, radiation and medicines, such as chemotherapy and hormonal agents.
Surgery remains the most effective treatment for curing cancer.
Radiation treatments have become a technically sophisticated and effective approach for many patients both in the curative and palliative settings. Radiation is often used in combination with chemotherapy.
Chemotherapy generally refers to medicines that work by damaging cancer cell DNA or proteins. Cancer cells tend to be more sensitive to these drugs and less able than normal cells to recover from the damage. Since the 1950s, chemotherapy has been used in hundreds of combinations directed at specific tissue types.
Unfortunately, although some chemotherapy can be very effective, even curative, these medicines tend to have significant toxicity and are not precisely focused on just the cancer cells.
Q: What is molecular medicine?
A: Newer understanding of the molecular mechanisms in cancer has identified “targetable” lesions in the cell machinery of many cancers. We are moving away from defining cancer by what organ or body part it starts in and toward a description based on the molecular changes in the cell. We are also moving away from traditional chemotherapy and toward more use of newer antibodies and other molecules that are specifically damaging to the change in the cancer cell.
Q: Are there studies underway to expand the knowledge of molecular medicine?
A: The National Cancer Institute (NCI) is sponsoring a large clinical trial directed at analyzing a patient’s tumor makeup to see if there is the kind of gene abnormality present within the tumor for which a targeted drug exists. Simply knowing there is a gene mutation present doesn’t mean we know how to address that mutation. The clinical trial seeks to determine whether treating cancers according to their molecular abnormalities will show evidence of effectiveness.
Called the “NCI Molecular Analysis for Therapy Choice (NCI-MATCH) study,” it is for patients who have cancer that has progressed despite standard treatments and is open at many cancer centers around the country
Patients have their cancer analyzed at one of four central laboratories around the country. The tumor is tested for more than 4,000 different variants across 143 genes. If the cancer has an “actionable” mutation – meaning we can do something beneficial that will slow or stop the cancer – and if there is an appropriate targeted drug, then the patient will receive treatment. Unfortunately only about 20 percent of patients will have both an eligible mutation and drug pair.
The Baystate Regional Cancer Program has this study open and is actively accruing patients. One recent patient had an uncommon mutation found in the cancer cells. This patient is currently receiving an investigational drug designed specifically for the pathways controlled by this gene mutation.
Although it is early days in terms of this “precision” approach, oncologists are excited about the future. The lab research done decades ago may be paying off with effective new treatments now reaching the clinic.
Dr. James Stewart is the chief of hematology/oncology at Baystate Regional Cancer Program.