Immunotherapy and precision medicine are some of the most exciting terms in cancer today. If you don’t have cancer, you’ve probably heard about them on the news. If you do have it, you’ve probably heard them from your doctor.
Still, most people don’t know exactly what these terms mean, how they differ, and how they’re changing lives. That’s understandable. Immunotherapy and precision medicine are complex and evolving. Here’s what you should know about these hot topics in cancer research and treatment.
What’s Behind Precision Medicine?
This approach lets doctors select treatments that are most likely to help patients based on a genetic understanding of their disease.
In the world of cancer, that genetic understanding comes from something called tumor DNA sequencing. This is also known as genetic profiling or genetic testing. Doctors test a small sample of your tumor to learn more about the genetic changes that led to it become cancer.
With that knowledge, they can offer a treatment that specifically targets the things that caused your cancer and continue to make it grow. The genetic changes are also called mutations or alterations. The drugs that target them are known as targeted therapies.
David E. Fisher, MD, PhD, director of the melanoma program at Massachusetts General Hospital Cancer Center, describes targeted therapies this way: “You are aiming your gun directly at the engine that is driving that cell, as opposed to using a chemotherapy drug that will kill any cell that’s dividing, from cancer to hair follicle cells.”
One example of a targeted therapy is the drug imatinib (Gleevec). It blocks a protein involved in chronic myelogenous leukemia (CML). Patients with CML who take Gleevec can live in remission for decades, Fisher says.
If targeted therapies are at the heart of precision medicine -- delivering a treatment that attacks a specific mutation driving your specific cancer -- how does immunotherapy fit in? Fisher and other cancer experts say the merging of precision medicine and immunotherapy could be part of an exciting future for cancer treatment.
Where Immunotherapy and Precision Medicine Meet
Immunotherapy puts your immune system to work fighting cancer. Some treatments “mark” cancer cells so they’re easier for your immune system to find (and destroy). Others supercharge your immune system to fight cancer cells.
The strategy has been around for a very long time, going as far back as the 1890s. Long before immunotherapy became a buzzword, doctors have been using it to treat cancer patients. A few examples:
- Monoclonal antibodies, which trigger your immune system to fight cancer cells
- Adoptive cell transfer, in which doctors remove T cells (a type of immune cell) from the tumor and change them in the lab so they can go back in your body and fight cancer.
- Cytokines, which are proteins that play important roles in the body’s immune response
Now that we’re in the age of precision medicine, we can learn more than ever about what drives one person’s cancer. That could ultimately give doctors better insight about who could benefit most from immunotherapy drugs.
“Applying precision medicine to immunotherapy is doable. It would consist of using genomic information, or more likely using other information in the microbiome, to determine what combinations of immune drugs should be used,” says Jeffrey S. Weber, MD, PhD, deputy director of the Perlmutter Cancer Center at NYU Langone Health.
Leukemia and Lymphoma Breakthrough: CAR T
The reason immunotherapy has become such an exciting topic in recent years is because of some potential game-changers in the field. Some treatments mark the spot where precision medicine and immunotherapy meet. They look for changes to genes (the doctor will call them "mutations") that help cancer cells grow. The goal is to shut down the rogue cells without hurting normal ones.
One of these is CAR T-cell therapy, which stands for chimeric antigen receptor T-cell therapy. A receptor is a molecule on or inside a cell that binds to substances and changes the cell.
How it works: The doctor separates T cells from a sample of your blood. Doctors add the gene for the chimeric antigen receptor and the cells become CAR T cells. After they multiply in the lab -- so there are a lot of them -- they’re returned to your bloodstream where the receptor lets them bind to another antigen on cancer cells and kill them to fight cancer.
“CAR T is an adoptive cell therapy. It has tended to be only successful in hematologic malignancy [blood cancer],” Weber says.
If you have blood cancer, however, CAR T may be a ray of hope when other treatments stop working. In 2017 the FDA approved two CAR T therapies. One drug treats children and young adults who have acute lymphoblastic leukemia (ALL). The other treats certain adults with advanced lymphoma.
Success in Metastatic Melanoma and Other Cancers
Metastatic melanoma, also known as advanced melanoma or stage IV melanoma, is when the cancer cells spread to other parts of your body. Usually that means the liver, lungs, bones, and brain.
Fisher says advanced melanoma is the “poster child” for excellent response to immunotherapy. It’s one of the best responders to this form of cancer treatment.
Here’s how the treatments work:
Targeted therapy
This is another intersection of precision medicine and immunotherapy. The different types of treatment include:
BRAF inhibitors: About half the people with melanoma have changes in the BRAF gene. Melanoma cells that have these changes make an altered BRAF protein that helps them grow. Drugs that attack the BRAF protein, which can shrink or slow tumor growth, include:
- Dabrafenib (Tafinalr)
- Encorafenib (Braftovi)
- Vemurafenib (Zelboraf)
MEK inhibitors: The MEK gene works with the BRAF gene. MEK inhibitors include:
- Binimetinib (Mektovi)
- Cobimetinib (Cotellic), which is usually paired with vemurafenib
- Trametinib (Mekinist) which can be taken alone or paired with dabrafenib
C-KIT Inhibitors: Some melanoma tumors have changes in the C-KIT gene that help them grow. Drugs that target cells with changes in C-KIT include:
- Imatinib (Gleevec)
- Nilotinib (Tasigna)
Immunotherapy:
These treatments kill cancer and help your body fight it at the same time.
Anti-CTLA-4 inhibitor: It blocks a molecule called CTLA-4, a protein that stops T cells (white blood cells that help your body fight disease) from attacking healthy cells and cancer cells. They help turn T cells back on so they can fight melanoma cells:
- Ipilumumab (Yervoy)
Anti-PD1 inhibitor: These medications help T cells fight cancer. They’re also what doctors call checkpoint inhibitors. They make cancer cells easier for your immune system to see and fight more effectively.
- Pembrolizumab (Keytruda)
- Nivolumab (Opdivo)
Combination therapy: This pairs a medication that makes T cells better cancer killers with one that boosts your immune system and helps T cells grow. They can work better together than alone.
- Nivolumab (Opdivo) + Ipilimumab (Yervoy)
Interleukin-2: This drug boosts your entire immune system. It stops cancer cells from reproducing and spreading. It helps boost T cells and it makes cancer cells give off chemicals that attract killer cells:
- IL-2, Proleukin
Oncolytic virus therapy: It uses a genetically modified herpes virus (the cold sore virus) to kill melanoma cells in your skin and lymph nodes:
- T-VEC (Imlygic)
“Treating metastatic melanoma used to be a disaster, but now with ipilimumab and nivolumab, the landscape for patients is completely changed,” he says. “The median survival back 10 years ago was about 9 months and now it’s between 30 to 50 months.”
Other types of cancer that immunotherapy drugs are approved to treat include:
- Lung cancer
- Breast cancer
- Prostate cancer
- Kidney cancer
- Stomach cancer
- Bladder cancer
- Head and neck cancer
- Liver cancer
- Colorectal cancer
- Merkel cell carcinoma
- Myeloma
For all the success of immunotherapy, there is a downside: a laundry list of potential side effects. Flu-like symptoms include fever, dizziness, nausea or vomiting, and more. But, particularly in the case of aggressive cancers like metastatic melanoma, don’t let those deter you if your goal is a longer life. “The advice I would give is to move quickly with treatment,” Weber says.
