Targeted cancer therapy

This topic will discuss the different types and limitations of targeted cancer therapy...
Abdelwahab Ward, BS Pharm, PharmD
This article was written by: Alaa Khalid Said, BS Pharm, PharmD.
  • Senior oncology pharmacist,
    Clinical Pharmacy Department, Tanta Oncology Center.
OVERVIEW ã…¡ A new generation of cancer treatment has come to the forefront called targeted cancer therapies. Like conventional chemotherapy, targeted cancer therapies use pharmacological agents that inhibit growth, increase cell death and restrict the spread of cancer. Targeted therapy is a cancer treatment that uses drugs to target specific genes and proteins that are involved in the growth and survival of cancer cells. A targeted cancer therapy can be used by itself or in combination with other treatments, such as traditional or standard chemotherapy, surgery, or radiation therapy.

HOW DOES TARGETED CANCER THERAPY WORK

In our body, every tissue is made of certain type of cells that has its own job. Cancer starts when certain genes in healthy cell become abnormal over time making what called genetic mutation. To develop targeted therapies, researchers first identify the genetic changes that help a tumor grow and change. A potential target for this therapy would be a protein that is present in cancer cells but not healthy cells. This can be caused by a mutation. Once researchers have identified a mutation, they develop a treatment that targets that specific mutation. Targeted therapies can do different things when reach the cancer cells they target:
    • Block or turn off chemical signals that tell the cancer cell to grow and divide.
    • Change proteins within the cancer cells so the cells die.
    • Stop making new blood vessels to feed the cancer cells.
    • Trigger your immune system to kill the cancer cells.
    • Carry toxins to the cancer cells to kill them, but not normal cells.

HOW IS TARGETED THERAPY DIFFERENT FROM CHEMOTHERAPY

Targeted therapy drugs, like other drugs used to treat cancer, are technically considered as chemotherapy. But targeted therapy drugs don’t work the same way as traditional or standard chemotherapy drugs. This makes them work differently from chemotherapy in two key ways:
    • Because of their targeted action, these drugs have an effect on the cancer cells and mostly leave normal, healthy cells alone, where traditional chemotherapy is cytotoxic to most cells, that means it can damage normal, healthy cells in addition to damaging and killing cancer cells.
    • Targeted drugs often work by blocking cancer cells from copying themselves. This means they can help stop a cancer cell from dividing and making new cancer cells. Traditional chemotherapy, however, kills cancer cells that have already been made.

TYPES OF DIFFERENT TARGETED CANCER THERAPY

There are several different types of targeted therapy. The most common types are monoclonal antibodies or small-molecule drugs.

MONOCLINAL ANTIBODIES (mAb) ã…¡ They also called “therapeutic antibodies”, is the most successful protein-based therapy for cancer treatment. During the process of carcinogenesis, the undesired mutation activates the proto-oncogenes or inactivates tumor suppressor genes. The therapeutic antibodies specifically target the cancer cell surface receptors, and kill cancer cells via the mechanisms of antagonism, signaling, Complement Dependent Cytotoxicity (CDC) and Antibody- Dependent Cell-mediated Cytotoxicity (ADCC).

     Various monoclonal antibodies have been developed to treat different cancers. For example, the anti-breast cancer antibodies, trastuzumab (Herceptin) and pertuzumab (Perjeta), can block HER2 signaling protein kinase and phosphoinositide 3-kinase and inducing ADCC. The anti-colorectal cancer antibodies, bevacizumab (Avastin), cetuximab (Erbitux) and panitumumab (Vectibix), inhibit Vascular Endothelial Growth Factor (VEGF) and therefore block new blood vessel formation and cell proliferation. Rituzumab (Rituxan), ofatumumab (Arzerra) and obinutuzumab (Gazyva) are three antibodies targeting the B-cell surface antigen CD20. They used in treatment of Non-hodgkin’s Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), lymphomas and hairy cell leukemia via mediating B-cell lysis through ADCC, CDC and apoptosis.

SMALL MOLECULE DRUGS ã…¡ These drugs are tiny enough to enter a cancer cell once they find it. They work by targeting a specific substance inside the cell and blocking it which help in blocking cancer cell multiply and spread. Angiogenesis inhibitors are an example of this type of targeted therapy. Angiogenesis is the process for making new blood vessels. Tumor cells need blood vessels to bring it nutrients that help them grow and spread. Angiogenesis inhibitors starve the tumor by keeping new blood vessels from forming in the tissue around it. Immunotherapy and apoptosis inducers are also examples for small molecule drugs.

ARE THERE LIMITATIONS TO TARGETED THERAPY

As with any cancer treatment, targeted therapy may not be the best treatment choice for every person with cancer. It seems simple to use a drug for your specific cancer, but targeted therapy is complex, and it doesn’t always work. It is important to know that:
    • A targeted treatment will not work if the tumor does not have the target.
    • Having the target doesn’t mean the tumor will respond to the drug.
    • The response to the treatment may not last over time.
Targeted therapy is an important line in cancer treatment. But, so far, doctors can only treat a few cancers with targeted therapy. Most people with cancer also need surgery, chemotherapy, radiation therapy, or hormone therapy.

REFERENCES

Abdelwahab Ward, BS Pharm, PharmD