Research in targeted therapy
Researchers are developing and studying many targeted therapy drugs that can be used alone or in combination with other cancer treatments. In targeted therapy, drugs target specific molecules (for example, proteins) on the surface of or inside cancer cells. Some of these drugs block signals to the molecules that tell cells to grow or divide. This stops the growth and spread of cancer cells. Some targeted therapy drugs are already available to treat specific cancers, but researchers are studying many new targeted therapy drugs in clinical trials.
Targeted therapy is an important part of personalized (precision) medicine, which uses information about a person’s genes and proteins to prevent, diagnose and treat cancer.
Some key areas of research in targeted therapy are:
Finding cell changes that make good targets
Good targets are genes, proteins or molecules that cause cancer cells to grow and live. To develop targeted therapy drugs, researchers study the changes in cancer cells that cause cancer to grow. In normal cells, genes make proteins that cells need to stay healthy. But sometimes this can go wrong. For example, some genes make too many copies of themselves or combine (fuse) with other genes so cells start to grow and divide abnormally or live longer than they should. In the lab, doctors can test cancer cells to see which genes and proteins are normal and which aren’t. With this information, researchers try to develop new drugs that target abnormal genes and proteins in cancer cells while harming normal cells as little as possible.
Once a good target is found, the challenge is to design a drug to interfere with the target’s ability to help cancer grow. In some cases, researchers have found good targets but they haven’t yet found a drug that can specifically bind to the target in a way that blocks its function. This is one of the biggest challenges in developing targeted therapy drugs.
A number of targets are being studied in clinical trials.
BCL2 is a gene that prevents programmed cell death (called apoptosis). Some cancer cells make too much BCL2, which helps the cancer cells survive. Researchers are studying BCL2 inhibitors, which can bring about apoptosis, as a treatment for a number of different cancers.
Cyclin-dependent kinases (CDKs) are proteins that control the cell cycle. CDK inhibitors block these proteins to help slow or stop the growth of cancer cells. CDK inhibitors are showing promise for treating certain cancers that come back or that don’t respond to treatment.
FLT3 is a gene that can become mutated in certain cancer cells. FLT3 inhibitors are being studied to treat certain cancers alone or with other treatments.
Histone deacetylases (HDACs) are a family of enzymes involved in regulating the amount and activity of a number of different proteins. Some types of cancer cells make too much of a histone deacetylase, which can cause the cancer to grow. HDAC inhibitors can prevent cancer cells from growing and dividing. Researchers are studying drugs that inhibit HDAC to see if they make certain chemotherapy drugs or radiation therapy work better by making cancer cells more sensitive to these treatments.
KRAS is an oncogene. It is involved in signalling and telling cells to grow and divide or to mature and differentiate. When mutated it can cause normal cells to become cancerous. It has been used as a biomarker for colorectal cancer and is also being studied as a possible target for other cancers.
c-MET is a protein that is produced in large amounts by a number of cancers.
mTOR is a protein that controls cell growth and division. This protein can trigger cancer cells to grow and new blood vessels (which cancers need to grow) to form. mTOR inhibitors block this protein and can be used to slow or stop cancer cell growth. mTOR inhibitors are approved for treating some types of cancers and are being studied in clinical trials to treat other types.
Poly (ADP-ribose) polymerase (PARP) is an enzyme that helps repair damage to DNA. PARP inhibitors block PARP so cancer cells can’t repair their DNA, which causes them to die. PARP inhibitors may also make cancer cells more sensitive to anticancer treatments. PARP inhibitors are being studied to treat certain cancers and to prevent or minimize resistance of cancer cells to treatments.
Phosphoinositide 3-kinase (PI3K) is an enzyme in cells that makes them grow and divide. In some cancers, PI3K is always turned on so the cancer cells continue to grow and divide uncontrollably. PI3K inhibitors work by switching off PI3K. Researchers are studying drugs that inhibit PI3K to see if the drugs will kill cancer cells or stop them from growing.
Combination targeted therapy
Targeted therapy drugs target specific proteins or genes on the surface of or inside cancer cells. Some cancers can express more than one mutated protein or gene. Clinical trials are looking at treating cancer with combinations of targeted therapies that work in different ways. Cancer cells can mutate and develop resistance to a particular targeted therapy. Treating cancer with more than one type of targeted therapy can help prevent resistance.
Testing approved drugs for other types of cancer
There are many targeted therapy drugs available to treat cancer. But these drugs are only approved to treat some types of cancer. Researchers are testing targeted therapy drugs in other cancers that have the same abnormal genes or proteins. For example, afatinib (Giotrif) is a tyrosine kinase inhibitor approved to treat lung cancer. It is also being studied in clinical trials to treat head and neck cancer and glioblastoma when they have come back. Important research involves using biomarkers, molecular subgroups and tumour molecular profiling to identify potential targeted therapy drugs for a specific type of cancer.
New ways to design clinical trials
Personalized medicine research has taken a different approach to the design of clinical trials. Basket clinical trials test one drug that targets a mutated protein or gene in people with any type of cancer that tests positive for the mutation. Umbrella trials test several targeted therapy drugs in a group of people with different gene mutations but the same type of cancer.
A gene involved in the control of cell growth and division that may cause the growth of cancer cells.
An oncogene may be a normal gene that has mutated (proto-oncogene), a normal gene with abnormal gene expression or a gene that comes from a cancer-causing virus.
Any cellular, molecular, chemical or physical change that can be measured and used to study a normal or abnormal process in the body. Biomarkers are used to check the risk for, presence of or progress of a disease or the effects of treatment.
For example, prostate-specific antigen (PSA) can be used as a biomarker for prostate cancer or blood sugar levels can be used to monitor diabetes.
Also called biological marker (a molecular biomarker may be called molecular marker or signature molecule).
A protein that speeds up certain chemical reactions in the body.
For example, enzymes in the intestines help to digest food.
After seeing a Canadian Cancer Society call for volunteers in a newspaper, Rosemary knew that this was her opportunity to get started.
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