Molecular Testing – Why Is This Important?

Molecular Testing for Targeted Treatments

Targeted therapy is a type of treatment that targets a cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. Targeted therapy includes drugs that are aimed at specific genes or proteins that are only found in cancer cells or the tissue environment that contributes to cancer growth and survival. It is often used along with chemotherapy and other cancer treatments to block the growth and spread of cancer cells. Not all tumors have the same targets, so doctors may run tests to match a cancer with the most effective treatment. A few targeted therapies are approved by the U.S. Food and Drug Administration (FDA) being used to treat stomach (gastric) cancer. In addition, there are clinical trials which are looking for additional targets and new drugs for those targets. Targeted therapies are a promising way to personalize stomach cancer treatment but note that resistance to treatment can develop and side effects can be an issue.

The “targets” of targeted therapy

To understand targeted therapy, it helps to understand how cancer cells develop. Cells are the building blocks of every tissue in the body. There are many different types of cells, such as blood cells, brain cells, and skin cells, which each have specific functions. Cancer begins when specific genes in healthy cells mutate or change. Genes tell cells how to produce proteins, many of which help a cell function normally. However, if the genes are mutated, the proteins will be changed as well, resulting in abnormal cell division or delayed cell death. This causes the cells to grow uncontrollably, forming a mass called a tumor.

By studying cancer cells and how they react to their environment, researchers are finding that specific gene mutations contribute to the development of specific cancers. With this knowledge, they are developing drugs that:

  • Block or turn off signals that tell cancer cells to grow and divide
  • Turn on or promote processes that result in natural cell death
  • Deliver toxic substances specifically to cancer cells to destroy them

Types of targeted therapy

There are three main types of targeted therapy:

1. Monoclonal antibodies- These substances, which are made in the laboratory, block a specific target on the outside of cancer cells or in the tissue surrounding the cancer. Think of this as placing a protective plastic plug into an electrical socket to prevent electricity from flowing. Monoclonal antibodies can also deliver toxic substances, such as chemotherapy and radioactive substances, directly to cancer cells. These drugs are usually given intravenously (by IV) because they are large compounds that are not absorbed well by the body.

2. Oral small drugs- These drugs are usually given in the form of a pill that a patient takes by mouth. The body can absorb these better because they contain smaller chemical components than monoclonal antibodies (see above). These oral drugs usually block processes inside cancer cells that stimulate them to multiply and spread.

3. Angiogenesis Inhibitors- There is also a class of targeted therapy drugs called angiogenesis inhibitors that target the tissue that surrounds a tumor. These drugs focus on stopping angiogenesis, which is the process of making new blood vessels. Because a tumor needs the nutrients delivered by blood vessels to grow and spread, the goal of anti-angiogenesis therapies is to essentially “starve” the tumor by blocking the development of these new blood vessels.

Matching a patient to treatment

Recent studies show that not all tumors have the same targets, which explains why a targeted treatment does not work for every person. Researchers have learned that about 20% to 25% of all stomach cancers have too much of a protein called human epidermal growth factor receptor 2 (HER2), which fuels tumor cell growth. Gastric cancer patients should have their tumor tested for HER2 so doctors can provide the most effective treatment and not expose patients to unnecessary side effects and costs with drugs that are not likely to be helpful. If the results show that the cancer is HER2 positive, there are several FDA-approved drugs that may be recommended as treatment options including Trastuzumab (Herceptin) and there are several clinical trials being conducted as well.

To find the most effective treatment, your doctor should order tests to identify the genes, proteins, and other factors unique to your tumor. Because many of these treatments have some degree of side effects and the treatments can be expensive, doctors are making efforts to match each patient’s tumor to the most effective treatment whenever possible.

There are a number of targeted therapies that have been approved to treat different types of cancer but remember that a targeted treatment will not work if the tumor does not contain the target. However, remember that the presence of the target also does not guarantee that the treatment will work. Talk with your doctor or another member of your health care team for more information about your treatment options.

Challenges of targeted therapies

Although the idea of targeting a drug to a tumor seems straightforward, this approach is complicated and not always effective. For example, the target in the cancer cell may turn out not to be as important as first thought, and the drug will not provide much benefit to patients. Or, the cancer may become resistant to the treatment, meaning it no longer works, even if it did at first. Finally, these drugs may cause serious side effects, although the side effects are usually different than those seen with traditional chemotherapy. For example, patients receiving a targeted therapy may develop skin, hair, nail, eye, and/or heart problems and others.

Although the development of targeted treatments is a breakthrough in cancer treatment, only a few cancers can be eliminated with these drugs alone. With a few exceptions, patients with cancer usually receive a combination of targeted therapy and surgery, chemotherapy, radiation therapy, and/or hormonal therapy. As doctors gain more knowledge about specific changes in cancer cells, more targeted treatments will be developed.

Tumor Banking

If you are suspected of having gastric cancer and are undergoing a diagnostic work-up or surgical procedure, ask your treatment team in advance about molecular testing and tumor banking. Tumor banking preserves the tumor for future tests which will determine whether targeted therapies can work. This could be necessary if the cancer recurs or if the patient is already being treated for advanced disease, to test the usability of new agents as they are introduced. All cancer centers involved in treating gastric cancers should be familiar with molecular testing and offer it to their patients as a routine procedure.