Summary: New targeted cancer therapies have been highlighted this month as emerging technologies to fight tumors, and scientists have much more in the pipeline. [This article first appeared on LongevityFacts. Author: Brady Hartman. ]
Targeted cancer therapies – the most famous of which are immunotherapies such as CAR T-cell therapy – are the current focus of excitement in cancer treatment. New therapies and developments in the immunotherapy field prompted the National Cancer Institute (NCI) to update their guidance on targeted cancer therapies a little over a week ago. As the NCI says,
“Many targeted cancer therapies have been approved by the Food and Drug Administration (FDA) to treat specific types of cancer.”
The agency adds that other targeted therapies are being studied in clinical trials, with more being tested on lab animals.
Targeted Cancer Therapies
Targeted therapy focuses on the changes in tumors that help them grow, divide, and spread. As scientists learn more about the cellular changes that drive cancer, they are better able to design promising therapies that target these changes or block their effects. For example, a little more than a week ago, researchers cracked a significant part of the code to the epigenetic changes that cause cancer.
Targeted cancer therapies are medications or other substances that interfere with so-called “molecular targets” – Or as the NCI says, “specific molecules that are involved in the growth, progression, and spread of cancer.” Targeted cancer therapies are sometimes called “precision medicines,” “molecularly targeted therapies,” “molecularly targeted drugs,” or similar names.
Targeted therapy is the cornerstone of precision medicine, in which doctors combine genetic profiling with data to pick the optimal treatment for a particular patient. There are many types of cancer therapies, and oncologists try to select the best one for a specific type of cancer and its stage of progression. Most patients have a combination of conventional treatments, such as surgery with radiation therapy and chemotherapy. Patients may also receive targeted therapies such as immunotherapy or hormone therapy.
According to the NCI, targeted therapies differ from conventional chemotherapy in several aspects:
- “Targeted therapies act on specific molecular targets that are associated with cancer”, whereas most conventional chemotherapies work on all rapidly dividing cells, including both normal and cancerous ones.
- Targeted therapies are deliberately chosen or designed to interact with their target, whereas many standard chemotherapies were identified because they kill cells.
- Targeted therapies are often cytostatic, meaning they block the proliferation of tumor cells, whereas standard chemotherapy agents are cytotoxic, meaning that they kill cancer cells.
Most targeted therapies are either small-molecule drugs or monoclonal antibodies. Small-molecule drugs are small enough to enter cancer cells readily, so they are used for targets that are inside the cells. Monoclonal antibodies are not able to enter tumors easily. Instead, they attach to specific targets on the outer surface of cancer cells.
How Targeted Cancer Therapies Work
Most targeted therapies treat cancer by interfering with specific proteins that help tumors grow and spread throughout the body. They treat tumors in different ways, including causing cell death, delivering deadly payloads to cancer cells, starving tumors of the hormones it needs to grow, blocking the formation of new blood vessels, stopping tumors from growing, and helping the immune system locate and destroy tumors.
Cause Cell Death
Healthy cells die in an orderly process called apoptosis when they are no longer needed or become damaged. However, tumors have ways of avoiding this fate. Some targeted therapies can induce cancer cells to undergo cell death. For example, consider Daratumumab a newly approved treatment for multiple myeloma, a blood disease that is more prevalent among the elderly. Daratumumab is a first monoclonal antibody that binds to cancer cells and causes them to commit suicide via apoptosis. In November 2015 the FDA approved the drug under the tradename Darzalex to treat people with multiple myeloma. The drug is jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech. According to studies, combining Daratumumab with other cancer drugs makes it more effective against multiple myeloma.
Deliver Deadly Payloads to Tumors
Some monoclonal antibodies are combined with toxins, chemotherapy drugs, and radiation. Once these monoclonal antibodies attach to targets on the surface of cancer cells, the cells take up the cell-killing substances, causing them to die. Cells that don’t have the target will not be harmed.
Starve Tumors of Necessary Hormones
Some prostate and breast cancers require specific hormones to grow. Hormone therapies are a type of targeted therapy designed to work in two ways. Some of these therapies prevent the body from making particular hormones. Others block the hormones from acting on the cells, including cancer cells.
Block the Formation of New Blood Vessels.
Tumors need to create new blood vessels to grow beyond a certain size. These blood vessels develop in response to signals from the cancer cells. Without a blood supply, tumors stay small. Some targeted therapies are designed to interfere with these molecular signals, preventing blood vessels from forming. Or, if a tumor already has a blood supply, these treatments can kill existing blood vessels, causing a cancer to shrink.
Stop Tumors from Growing
Healthy tissues in the body usually divide to make new cells only when instructed to do so by molecular signals. These signals bind to proteins on the cell’s surface, telling them to divide. This process helps new cells form only as the body needs them. These surface proteins must be present for a healthy cell to divide, cancer cells have corrupted the process. However, some cancer cells have changes in their surface proteins, instructing them to divide in the absence of signals. Some targeted therapies interfere with these surface proteins, preventing them from notifying the cells to divide. This process helps slow the uncontrolled growth of a tumor.
Help the Immune System Destroy Tumors
One reason that tumors thrive is that they can hide from a flagging immune system. According to a controversial new study, the shortcomings of our aging immune system explain cancer better than genetic mutations. Cancer immunotherapies help bolster the immune system so it can better fight cancer.
Certain targeted cancer therapies can mark tumors, so it is easier for the immune system to find and destroy them. Checkpoint inhibitors are the most notable example of successful cancer immunotherapies. Other targeted therapies – such as CAR T-cell therapy – help boost the immune system to work better against cancer.
CAR-T cell therapy is among the most exciting of immunotherapies and involves removing immune system cells from a patient and supercharging them using gene editing to fight cancer more effectively. CAR stands for chimeric antigen receptors and has shown remarkable results in treating blood cancers, especially leukemia. Moreover, using T cell therapy in treating a form of cancer called lymphoma is showing promise. As a recent article explains, there are many clinical trials testing T cell therapy for various types of cancer.
Targeted Cancer Therapies in the Pipeline
Many novel approaches to cancer are being tested on lab animals. Researchers are increasingly focusing on the epigenetics of cancer. The epigenetic program plays a role in aging and disease and is the master set of instructions which rides herd over our genetic code. For example, researchers at CWRU have successfully used gene enhancers to stop the spread of cancer throughout the bodies of lab mice. In another example, researchers at the University of Zurich just announced that they developed a novel stealth technique that fights cancer when combined with gene editing. In another example, a team of researchers in Barcelona just showed a new technique that enables the immune system to recognize and begin fighting colon cancer in mice. The treatment was so successful that it inhibited the tumors from spreading, or metastasizing to other parts of the body. Moreover, for those cancers that had already spread, the treatment enabled the immune system to eliminate them quickly.
And while CAR T-cell therapy holds promise to treat cancer, the procedure is labor-intensive and expensive. Researchers at Stanford University are working on a novel way to boost the immune system to fight cancer by injecting tiny amounts of immune-stimulating agents directly into the tumors of mice. This technique bypasses the labor of CAR T-cell therapy with the goal of achieving a similar effect. The Stanford University researchers reported that activating T cells in tumors destroyed most traces of cancer in mice, and are recruiting lymphoma patients to test the idea in a clinical trial.
While all of these preclinical therapies have shown promising results in mice, researchers are uncertain whether they will do the same for humans. Many treatments have shown good results in lab animals only to be disappointing when tested on people in clinical trials.
- Breakthrough cancer immunotherapies to be ‘curative’ by 2025 says research head.
- Scientists develop cancer-seeking nanorobots that search out and destroy tumors.
- Precision cancer treatment trials report good results in treating tumors.
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Cover Photo Credit: Canva.
“Targeted Therapy to Treat Cancer.” National Cancer Institute. August 15, 2014. Web. Retrieved Feb 16, 2018. Link to article on NCI.
“Targeted Cancer Therapies.” National Cancer Institute. Reviewed: February 9, 2018. Web. Retrieved Feb 16, 2018. Link to article in NCI.
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