Targeted Therapies Take Aim at Cancer
All anticancer medicines target tumors in some way. But conventional treatments attack healthy cells as well as cancer cells. As a result, there can be serious side effects from the treatment. A new approach to cancer treatment may help reduce side effects. The new treatment is called targeted therapy. It takes a more direct aim at cancer cells. And that can means less damage to healthy cells.
Targeted therapies are designed to see a specific molecular change in a cancer cell that drives the growth and spread of a tumor. By zeroing in on its molecular target, these new medicines destroy or slow the growth of cancer cells but don't affect normal, healthy cells. And because healthy tissues are spared, targeted therapies tend to bring about fewer and less severe side effects than conventional treatments.
How knowing the problem can lead to the treatment
Trillions of cells make up the normal, healthy body. Cells grow and divide in a controlled manner according to a complex system of chemical signals within the cells. These signaling pathways tell cells when to divide, when to be at rest, and even when to die. Such signals help each tissue and organ in the body maintain its proper shape and function.
If a problem arises in a cell's signaling system, it can push a healthy cell toward becoming a cancerous one. Usually, more than one signal has to go haywire for a tumor to arise. But over time, if a number of critical molecular changes accumulate, the healthy cell is transformed into a cancer cell.
Scientists have found many molecular mistakes that lead to cancer. Defects in genes are a very common molecular change seen in cancer. Genes are stretches of DNA located within cells. The role of genes is to provide cells with instructions for making proteins. Damaged genes make flawed proteins. Many proteins are involved in signaling. So flawed proteins disrupt the signaling pathways that are needed for a cell to function normally.
Finding the exact mistakes that lead to cancer can help doctors and researchers know how to treat cancer. Once a critical flaw has been found, researchers search for a medicine that can block with an abnormal molecule or process. The medicine's block of the process can help stop the cancer from getting worse or even get rid of the tumor.
Types of targeted therapy
Some targeted therapies aim at tumors by seeking out molecules found only in cancer cells. Other targeted agents seek out molecules that are more abundant in cancer cells than in healthy cells. And still other treatments are focused on processes that are more important to the growth of cancer cells than normal cells.
There are two main classes of molecularly targeted medicines under development. They are small molecule compounds and monoclonal antibodies.
Small molecule compounds
Small molecule compounds are medicines that interfere with the molecular process of cancer cells that can cause them to die or stop their growth. Many of these medicines can be taken by mouth.
One example of a small molecule compound is imatinib. It's used to treat a rare stomach cancer called gastrointestinal stromal tumor (GIST) and certain types of leukemia.
Chronic myelogenous leukemia (CML) is an unusual type of cancer in that only one molecular defect is needed to turn a normal cell into a cancerous one. The problem arises when two genes fuse together and make an abnormal protein. This protein sends a signal to the cell that tells it to grow in an uncontrolled manner. Imatinib controls the growth of CML tumors by preventing the abnormal protein from signaling the cancer cells to grow.
Imatinib also works against other tumors that have defects in proteins similar to the one involved in CML.
Many other small molecularly targeted therapies are being created. Erlotinib was approved by the FDA to treat metastatic non-small cell lung cancer and pancreatic cancer in certain cases or tumor types. Erlotinib works by blocking a protein called the epidermal growth factor receptor (EGFR) from signaling the cell to grow. For this reason, it is classified as an EGFR inhibitor. EGFR is made in large amounts by many tumors, such as those found in lung, breast, head and neck, pancreas, and colon cancer. But tumors that have certain mutations in EGFR are treated best with erlotinib. In advanced stage lung cancer, for example, EGFR mutated lung cancer is better treated with erlotinib than with standard (nontargeted) chemotherapy. Whether a lung cancer has this EGFR mutation can be learned by a special molecular test done on the tumor (biopsy). Because other molecular defects cause these cancers, more than just one medicine will likely be needed to control or destroy these tumors.
The second category of targeted therapies is monoclonal antibodies. Antibodies are normal parts of the immune system that help rid the body of foreign invaders or infectious germs such as bacteria. Antibodies recognize abnormal surface patterns or antigens on the invader.
Antibodies trigger the body's immune response to an invader. They are programmed to remember previous invaders so that they can quickly destroy them if they attack the body again.
Monoclonal antibodies are made in a lab. They work in a similar way to the body's natural antibodies. They find and bind to antigens found on cancer cells and get rid of them. Monoclonal antibodies can be used alone to stimulate an immune response. Or they can be used to deliver medicines, toxins, or radioactive material directly to a tumor.
Here are a few monoclonal antibody therapies approved by the FDA:
Bevacizumab has been approved the first treatment for metastatic colorectal cancer, meaning the cancer has spread. It also used to treat other tumors, including certain lung, brain and kidney cancers. It is the first medicine to be approved that works by targeting angiogenesis,. This is the formation of new blood vessels to the tumor.
Cetuximab has been approved for some cases of head and neck cancers, and colorectal cancers. It is thought to work by targeting the epidermal growth factor receptor (EGFR) on the surface of cancer cells.
Trastuzumab is used to treat breast cancer. This medicine targets a protein on breast cancer cells called the human epidermal growth factor receptor-2 (HER-2). Trastuzumab only works against breast tumors that make too much HER-2 protein. It has also been approved to treat some gastric and gastroesophageal junction tumors.
Rituximab is used to treat B-cell non-Hodgkin lymphomas that carry a protein called CD20.
Ibritumomab tiuxetan binds to the same CD20 target that Rituximab does, so it's used to treat the same types of cancer. But ibritumomab carries an additional punch because its monoclonal antibody is tied to a radioactive compound called yttrium-90, which can kill cancer cells. By delivering this damaging compound directly to the tumor, ibritumomab allows larger and more deadly doses of the radioactive medicine to reach the tumor. But it keeps any damage to healthy cells to a minimum.
Ofatumumab is used to treat chronic lymphocytic leukemia. It is directed against the CD20 cell surface antigen.
Ipilimumab is used to treat advanced melanoma. It is directed against a T-lymphocyte-associated antigen-4 (CTLA-4), located on the surface of activated T cells.
Realizing a vision
In time, researchers hope to make specific treatments for each person with cancer. By testing a person's tumor cells to find the exact molecular problems, the doctor would choose a combination of therapies to take specific aim at the major defects in the cells of the tumor.
Before this can be done, existing targeted therapies must be refined, new targets and therapies must be found, and the right combinations of medicines must be developed. While science is only at the beginning of this revolutionary approach to cancer treatment, researchers are working toward making this vision a reality.
June 09, 2018
LoCicero, Richard, MD,Sather, Rita, RN