William Miller, MD
Cancer Treatment - Part 2: New Horizons
Last week we looked at the history of cancer treatment from ancient times to modern day. We saw how surgery has played the key role in curing cancer if it is detected before it starts to spread. We also looked at the development of cancer drugs, so called chemotherapy, for treating cancer after it has spread or may have spread. We ended on the observation that since chemotherapy has many side effects, the next generation of drugs would need to be both more effective and better tolerated.
Dr. Vandana Sharma has witnessed the development of many new approaches to cancer during her career as an oncologist. “We have gone from a really aggressive approach that involved basically bathing all of the cells of the body with toxic chemotherapy, now to a more nuanced approach where we can direct the treatments specifically to the cancer cells,” she said. Sharma is the medical director of the Oncology Clinic at AHMC in Ft. Bragg.
There are several categories of such treatments. All are currently in use today to treat a wide variety of cancers. Many of these treatments also involve a shift in the treatment goal away from attempting to eradicate the cancer completely, which still usually involves exposing the patient to strong chemotherapy agents with many side effects. Instead, the goal of treatment becomes simply inactivating the cancer or keeping it locked in a suppressed state where the person can live out a normal life even through the cancer is technically still present.
“These new targeted treatments, often called directed therapy, can greatly improve survival in metastatic cancer (cancer that has spread). So, while the patient may still have the cancer, it is held in check and not causing problems. Since these treatments tend to have less side effects, the treatment is better tolerated and quality of life is improved. This is important since the patient may have to be on these drugs for extended periods of time, even for life,” Sharma said. Many of these new treatments are taken as a pill, thus avoiding the need to get a periodic IV infusion.
The first directed therapy approach is to couple the chemotherapy agent to an antibody that is specifically targeting the cancer cells. Once the antibody attaches to the cancer cell, it delivers its “payload” to the area just around the cancer cell. This approach is known as “precision medicine” and allows extremely small amounts of the chemotherapy to be given which then concentrate only around and in the tumor, thus avoiding exposing normal cells to the chemotherapy agent.
The second category of treatment is that of “immune modulators”. Our immune system has cells called natural killer lymphocytes or NK-cells. NK-cells have many important jobs. In addition to identifying and destroying cancer cells, they also help clear the body of aging cells and destroy cells transformed by viral infections. The first immune modulators were simply those naturally occurring substances that activate NK-cells, such as interleukins and cytokines. These are not tolerated well since the inflammatory response occurs throughout the body. Imagine feeling like you have a bad case of the flu that lasts for weeks after each treatment. Newer immune modulators are designed to change the chemical environment around the cancer cells so that the NK-cell activation is more localized to just the area in and around the tumor. Thus, they don’t cause as much flu-like side effects and are better tolerated. These newer immune modulator treatments are known as “microenvironment altering therapies”.
Another microenvironment approach is to cut off the tumor’s blood supply. As a tumor grows, it stimulates nearby blood vessels to grow into it and supply it with oxygen and nutrients. These treatments block that effect and deprive the tumor of what it needs to live and grow.
The next set of directed therapies are called “small molecule inhibitors”. These are drugs that turn off the mutated genes that gave rise to the cancer in first place. All cancer starts with a mutation in a normal cell’s DNA. In fact, there is usually more than just one mutation involved. As a result of these mutations, replication of the cell is inappropriately turned on, producing a small mass of cells that eventually grow into a tumor. Small molecule inhibitors work by turning off that inappropriate activation, thus putting the cancer cells in a state of suspended animation or triggering "programmed cell death," which causes the cancer cells to die.
An important part of directed therapy is identifying the unique qualities of each patient’s own cancer which then can guide treatment choices. This often involves testing for what receptors the tumor may be expressing on its surface. This is particularly important in breast cancer. If the tumor has receptors to hormones like estrogen and progesterone, that are involved in normal breast cell growth and function, then depriving the tumor of these hormones can be used as a treatment. This is referred to hormonal therapy and is also commonly used to treatment prostate cancer by blocking testosterone.
Having said all this, there are still patients who will require standard chemotherapy treatment. In these cases, the characteristics of their cancer show that one of the above treatments will not work as well and it is better to attempt to eradicate the cancer with conventional treatments. It is reasonable to expect that as research progresses, even these cancers will have less toxic and more effective treatments. To end on one such investigational treatment, the same mRNA vaccine techniques that have given us the Moderna and Pfizer COVID vaccines can be used to help the immune system generate antibodies against cancer, giving us a vaccine against cancer. It also may be possible to use this technology to deliver mRNA specifically to cancer cells. Once internalized into the cancer cell, it can program the cell to shut down or possibly even revert back to a normal cell. Such treatments are on the near horizon and are expected to be available in the next ten years or so.