Cancer is more complex than we ever imagined. We now know that the majority of cancers result from multiple genetic changes (mutations) that drive the abnormal behavior of the body’s cells.
These driver mutations vary, and cancers that look identical under the microscope can have different genetic drivers. Our rapidly expanding knowledge of driver mutations represents both a great opportunity and a major challenge.
This news creates an opportunity to develop treatments that focus on the driver mutations. The goal is to take away the driver’s license of these driver mutations by blocking their effect.
In the best cases, such targeted therapies make the cancer cells revert to a normal status. The cancer just melts away.
Unfortunately, cancer is complex. These driver mutations are present in only a small percentage of cancers, any given targeted therapy will only be effective in a small percentage of cancers.
Driver mutations usually don’t occur alone. Multiple drivers are often involved. So, even if we block one driver mutation, others can often take the wheel. In such a case, the cancer grows resistant to the targeted therapy and moves forward.
We have learned there is an additional level of complexity. Just as everyone has unique characteristics such as height, eye color, musical aptitude, and tendency to develop hay fever, the individual genetic makeup of patients can impact how each person responds to cancer and cancer therapy.
We need to address the complexity of the individual and the cancer to determine which treatment (in many cases it will be a combination of treatments including targeted therapies) is best for individual patients. To achieve this goal, we need to understand the molecular make up of individual cancers more thoroughly and how this genetic make up impacts on outcome and response to therapy.
The Sea Change
This is where the MERs come in. MER stands for Molecular Epidemiology Resource.
When patients with certain cancers have surgery or a biopsy, we ask them if they are willing to participate in a MER. If they agree, we collect a blood sample (to assess their overall genetic makeup) and a tumor sample (to assess the genetics of the cancer). We follow them through their cancer journey and track what treatments they receive and how well each treatment works. We also collect information on quality of life and other health problems.
By looking at the genetics of the individual’s blood and of the cancer cells, and how they impact outcomes over time for many patients, we are beginning to sort out the factors that determine whether a given treatment is going to work for an individual patient. For example, we recently found that a protein called complement factor H may influence how well a therapy for lymphoma works.
The MERs are also providing important clues as to which driver mutations we should target with our next generation of treatments.
Some Further Hurdles
The MERs, like the genetic differences they are assessing, are complex. They are also expensive. They require a commitment over many years from not only the patients but also from surgeons, pathologists, geneticists, computer scientists, and many other researchers.
At Holden Comprehensive Cancer Center, we have been developing a series of MERs over the past 10 years in lymphoma, melanoma, sarcoma, breast cancer, and pancreatic cancer. To date, more than 3,000 patients have agreed to be part of the MERs.
Next up will be a MER that focuses on cancers of the urologic organs (prostate, bladder, kidney). There is no doubt the investment of money and effort is worthwhile. We are already seeing the MERs become more valuable scientifically as they mature and grow larger.
While solving the complex driver mutations will be a challenge, we may find answers within the growing MERs data to effectively take away the driver keys and stop the cancer.
What It’s All About
The information provided by the MERs and other research projects are leading to a sea-change in how we treat cancer, but such change takes time, which is something many cancer patients don’t have. Each and every day, we need to provide the best possible care to our patients. Today, this includes standard approaches to cancer therapy such as surgery, radiation therapy and chemotherapy, as well as newer approaches to therapy such as immunotherapy and increasingly therapy targeted to the drivers outlined above. Tomorrow… who knows where the sea change will take us?
In future blogs, we will discuss in more detail where this sea change is taking us in the research laboratory and, most importantly, for patients.
George Weiner, MD
Holden Comprehensive Cancer Center Director