Targeted therapies

A targeted therapy is a drug that pinpoints specific abnormal molecules within the cancer cells to slow or stop the growth of these cells.

The most commonly used targeted therapy is HER2 inhibitor therapy. Other targets are beginning to be found and are increasingly being used, especially to reduce the risk of recurrence or to treat metastatic cancer that no longer responds to other conventional treatments.

Many targeted drugs are being investigated to improve breast cancer treatment.

Therapies targeting the HER2 gene inhibit this receptor and block its ability to proliferate. They are used to destroy tumours with strong HER2 gene expression in order to slow or stop the cancer’s progression. This treatment is often administered after surgery and radiation therapy to prevent the risk of recurrence.

The side effects are usually less severe than for other treatments, since targeted therapies only affect the cancer cells. Side effects of hormonal therapy include:

• Headaches
• Fatigue
• Diarrhea or constipation, nausea and vomiting
• Mouth sores
• Infection
• Red, dry or itchy skin
• Loss of appetite

Trastuzumab is one such agent. Sometimes this drug may cause heart damage, especially when given in combination with Doxorubicin, a chemotherapeutic agent. Cardiac tests may therefore be recommended before taking Trastuzumab to ensure this treatment will be safe.

Here are some of the available agents in this therapeutic class:

• Trastuzumab (Herceptin) has been available since the late 1990s and has greatly improved the prognosis of HER2-positive cancers.
• Pertuzumab (Perjeta) has been used more recently to treat metastatic breast cancer.
• Trastuzumab Emtansine (Kadcycla) is a newer agent used to treat metastatic breast cancer. It combines Trastuzumab and Emtansine, a chemotherapeutic agent. As a result, the chemotherapy targets cancer cells more precisely.

Research continues to improve HER2-targeting therapy. For example, resistance to Trastuzumab is often observed after one year of use. Treatments to counter this are currently being developed. Also, studies are underway on Pertuzumab and Trastuzumab Emantansin to test their effectiveness in treating early breast cancer and their effect when given in combination with other treatments. New antibodies under investigation (such as Margetuximab) 

Several cellular pathways are involved in the progression of breast cancer. Acting on these pathways may slow or stop the progression of the cancer.

The targeted therapies, other than HER2 inhibitors, are: (liens vers tableaux)

• Tyrosine kinase inhibitors
• Cyclin-dependent CDK4 and CDK6 kinase inhibitors
• PI3K-Akt-mTor intracellular signalling pathway inhibitors

Studies are underway on the use of these drugs for different types and stages of breast cancer. Several drug molecules targeting these pathways are being developed and the efficacy of combinations of different strategies is also being studied.

Targeted therapies under investigation include:

• Histone deacetylase inhibitors (HDACs) 
• Steroid sulfatase inhibitors 
• EGFR inhibitors 
• Farnesyltransferase inhibitors