Understanding the Role of Personalized Medicine

Growing knowledge about the genetic makeup of tumors is leading to a revolution in cancer treatment.

Through research, more effective tailored cancer treatments are now available. This means that we are beginning to move away from the use of “one-size-fits-all” chemotherapy and toward the use of targeted drugs designed for specific patients and tumors––that is, personalized medicine.

For many years, doctors knew that certain groups of people benefited from certain types of treatments. For example, older women with breast cancer tended to benefit more from hormone treatments than younger women with breast cancer. But in recent years, scientists discovered that not all cancers are alike. There are variations of each type of tumor. This was discovered when researchers focused on the genetics of tumors. Our genes are the blueprint for control of every cell in the body. A better understanding of this blueprint means we can find out how different types of tumors work, how they grow, and how to stop them from growing.

Medicines are being designed to target a number of different tumor cell growth mechanisms. With targeted drugs, doctors can select the treatment that is most likely to work for a certain patient and his or her particular type of tumor. This information also means that people for whom the drug would not work can avoid taking it and risking side effects.

How Targeted Treatments Work

Standard chemotherapy drugs are powerful medications that can kill cancer cells. They offer an effective way to treat tumors, but they can also harm healthy tissues. One day, targeted treatments may replace chemotherapy. But for now, doctors will continue to use chemotherapy, sometimes in combination with targeted drugs. (In some cases, doctors combine two targeted treatments without chemotherapy.)

There are many targeted treatments already available, and many more drugs are being studied in laboratories and clinical trials. A number of these medications are oral drugs, which are easier and more convenient for patients to take. To kill a cancer cell, targeted treatments disrupt many different types of cell mechanisms.

Drugs made of small molecules are able to get past the tumor cell’s outer layer and interfere with cell growth from the inside. These small molecules block signals from proteins that tell cancer cells to grow and divide. (Proteins are controlled by genes.) This type of targeted treatment can help stop tumor growth and may cause cancer cells to die.

Examples of small-molecule targeted treatments include dasatinib (Sprycel), which is approved by the U. S. Food and Drug Administration (FDA) to treat people with chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia, and nilotinib (Tasigna), which is approved to treat some people with CML.

Other types of small-molecule drugs disrupt tumor cells by changing some of their cell functions or by directly causing their death in a process known as apoptosis. Two examples are romidepsin (Istodax), approved by the FDA for the treatment of cutaneous T-cell lymphoma, and bortezomib (Velcade), approved for the treatment of multiple myeloma.

Some small-molecule drugs block the growth of blood vessels to tumors. To grow beyond a certain size, tumors must have a blood supply to get oxygen and nutrients. Treatments that interfere with the formation of these blood vessels may block tumor growth. An example of this type of drug is pazopanib (Votrient), approved by the FDA for the treatment of advanced kidney cancer.

Monoclonal antibodies track down tumor cells and bind to their surface to disrupt the cells’ function from the outside. Made in the laboratory, monoclonal antibodies are a type of protein. Although they cannot get past a tumor cell’s outer layer, monoclonal antibodies can attach themselves to the cell surface and block its receptors, or doorways. When receptors are blocked, growth signals cannot get in and the cell dies. There are many types of monoclonal antibodies. Each type is designed to find a specific kind of tumor cell.

Sometimes, monoclonal antibodies are used to carry an anti-cancer medicine directly to the tumor cell to kill it. The advantage of using this technique is that the treatment bypasses healthy tissue and goes directly to the tumor. Brentuximab vedotin (Adcetris) is an example of an antibody combined with a targeted treatment. Hitching a ride on the monoclonal antibody, the drug enters the cell and kills it. Brentuximab vedotin is approved by the FDA for the treatment of Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma.

Some monoclonal antibodies are designed to trigger the immune system to fight the cancer. In the case of ipilimumab (Yervoy), the antibody seeks out a substance on tumor cells called CTLA-4, which blocks the immune system. By blocking CTLA-4, ipilimumab stimulates the immune system to attack melanoma cells. This medication has been approved by the FDA for treating melanoma that has spread.

The New Diagnostics

In cancer, a pathologist is the physician who diagnoses the type of tumor a person has by studying cells and tissues under a microscope. The pathologist also provides information on how the tumor may grow, its stage or grade, and other basic characteristics. But now, because of personalized medicine, pathologists have a new and important role to play: helping to guide oncologists in choosing the most effective personalized treatment.

There are a number of different tests that pathologists can perform to learn more about the genetics of a tumor and the subclass it belongs to. This information helps point the way to the best personalized treatment. Through a fairly new field called proteomics, powerful new tools are being developed to find the genetic features of tumor cells. The “proteome” (a blend of the words “protein” and “genome”) is all the proteins our genes make; proteins do most of the work in cells. The genome is our complete genetic material.

New technologies allow pathologists to extract genetic material from stored tumor samples and to sort out thousands of pieces of genetic material in new tissue samples from a tumor. These techniques enable doctors to identify specific genes. It is a rapidly growing area of medicine that is vital to cancer treatment.

With proteomics, doctors can also identify the proteins that govern how each person will process, or metabolize, drugs. This is another important part of choosing effective treatment. For example, those with a mutated (changed) form of the DPD gene have difficulty metabolizing 5-fluorouracil, a common anti-cancer drug. That’s because the mutated gene does not make the needed DPD protein. As a result, people with a mutated DPD gene experience more side effects from this chemotherapy. This drug is used to treat a number of cancers including breast, stomach, pancreas, and certain types of colorectal and head and neck cancers. If a doctor knows the patient has a mutated DPD gene, he or she can choose another treatment or reduce the dose of 5-fluorouracil. In another example, people who are “fast metabolizers” of anti-nausea drugs can be given a higher dose so the medicine will stay in their system longer and work better.

The more your doctor knows about your genetic makeup, the more effective treatment you can receive.

The Importance of Clinical Trials

The exciting advances in personalized medicine have all come about because of clinical trials and the thousands of people with cancer who have taken part in them. These studies also increase the knowledge of tumor genetics through blood and tissue samples examined by pathologists. Some clinical trials are designed to learn more about side effects and quality-of-life issues. Talk to your doctor about whether a clinical trial is right for you.

Here are a number of questions you should ask your doctor about clinical trials. You may want a friend or family member to sit with you during the discussion to take notes.

• What is the purpose of the study?

• What is the phase of the trial?

• What kinds of tests and treatments are involved?

• How do the possible risks, side effects, and benefits of the study compare with my current treatment?

• How might this study affect my daily life?

• How many visits per week or month will I need to make?

• How long will the study last?

• Is a hospital stay required?

• Who will pay for the treatment?

• Will I be reimbursed for any expenses, such as transportation?

• What type of long-term follow-up care is part of this study?

• How will I know that the treatment being studied is working? Will the results of the trial be given to me?

• Who will be in charge of my care?

• Are there other experts I can talk to about this study?

• Can I take the informed consent form home to talk it over with my family or partner?

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This e-booklet was made possible by a charitable contribution from Bristol-Myers Squibb.

The information presented in this publication is provided for your general information only. It is not intended as medical advice and should not be relied upon as a substitute for consultations with qualified health professionals who are aware of your specific situation. We encourage you to take information and questions back to your individual health care provider as a way of creating a dialogue and partnership about your cancer and your treatment.