Uterine Cancer Treatment: Targeted Therapy

The treatment of uterine cancer depends on various factors, such as the stage of the disease. Traditional approaches to uterine cancer treatment such as chemotherapy have shown to be less effective in treating more advanced cases of the disease.

Novel approaches such as targeted therapy have emerged as promising methods to improve treatment outcomes in such patients. Understanding targeted therapy is important to properly evaluate if this approach is suitable and effective for your condition.

Targeted therapy is a form of precision medicine. It refers to the use of drugs to target specific structures, such as proteins, on the surface of or within cancer cells. This prevents cancer cells from growing or spreading. Unlike chemotherapy which affects both healthy and cancer cells, targeted therapy specifically targets cancer cells. This greatly reduces the damage to healthy cells.

However, the success of targeted therapy relies on the ability to uncover proteins or mutations that only exist in cancer cells and not in normal, healthy cells. As such, biomarker testing is usually carried out to determine if targeted therapy is suitable for the patient.

Biomarker testing is a method to analyse if there are any biomarkers present in the tumor. Each patient’s cancer has its own unique make-up of biomarkers. Hence, it is essential for patients to undergo biomarker testing to identify if there are any biomarkers present that can be targeted by targeted therapy.

Furthermore, depending on the type and stage of cancer, targeted therapy can be used with different treatment goals in mind. Targeted therapy may be used curatively, palliatively to ease symptoms or to control the spread of cancer. It is typically used to treat advanced or recurrent cases of uterine cancer.

Targeted therapy drugs act on their targets through different mechanisms. They can be classified into two main classes — monoclonal antibodies and kinase inhibitors.

Monoclonal antibodies are laboratory-made proteins that mimic the immune system. These drugs act by targeting specific molecules present on cancer cells. This either directly kills the cancer cells or prevents their growth.

Human epidermal growth factor receptor 2 (HER-2) inhibitors

For uterine cancer, the primary target is a protein known as human epidermal growth factor receptor 2 (HER-2). HER-2 is found to be overexpressed in some uterine cancer cells.

Some monoclonal antibodies are able to target this protein specifically, making them particularly effective in treating advanced or recurrent HER-2-positive uterine cancer. This includes uterine sarcoma and uterine carcinosarcoma, which are the more aggressive forms of uterine cancer.

These monoclonal antibodies are typically used in combination with chemotherapy. One mechanism in which this works is through targeted delivery. Due to the specificity of the monoclonal antibodies, they can bind to the chemotherapy drug and deliver it to the cancer cells directly. This limits the damage to normal healthy cells, not only improving treatment outcomes but also reducing any side effects.

The most common HER-2 inhibitor used in the treatment of uterine cancer is trastuzumab, which is given as an intravenous (IV) infusion once every three weeks. It is often used with chemotherapy in the form of carboplatin and paclitaxel. Another common treatment administered is fam-trastuzumab deruxtecan. This involves the use of trastuzumab as a carrier, to deliver the chemotherapy drug deruxtecan to the cancer cells directly. Similarly, it is given as an intravenous (IV) infusion once every three weeks.

Angiogenesis inhibitors

Monoclonal antibodies can also function as angiogenesis inhibitors. Angiogenesis refers to the development of new blood vessels, which is essential for cell growth and division. Monoclonal antibodies can bind to certain proteins on cancer cells, preventing angiogenesis and therefore limiting their growth and spread. For uterine cancer, the most common drug of this class used is bevacizumab. It is administered once every two to three weeks as an IV infusion.

Kinases are proteins that are essential in ensuring normal cell growth and function. Certain kinases are more active in cancer cells, making them potential targets for cancer treatment.

Kinase inhibitors bind to these kinases and prevent them from functioning normally. These inhibitors are specific to the kinase which they bind to. On the other hand, there are drugs which can target multiple different kinases, known as multikinase inhibitors.

Kinase inhibitors function through two main mechanisms:

• Blocking angiogenesis: kinase inhibitors prevent cancer cells from developing new blood vessels which are crucial for their growth and development.
• Disrupting signalling pathways: kinase inhibitors bind to and prevent kinases from attaching to their target. This prevents signals from reaching other targets, thereby slowing cancer cell growth and division.

Common kinase inhibitors used in the treatment of uterine cancer include lenvatinib and cabozantinib. Lenvatinib is typically administered with immunotherapy in the form of pembrolizumab for cases in which chemotherapy has not been effective. It is administered orally and taken once daily. Cabozantinib is a multikinase inhibitor used in the treatment of advanced uterine cancer. It is given to patients once a day as oral tablets.

As a modern and novel approach to cancer treatment, targeted therapy has demonstrated great potential in treating uterine cancer. In particular, it has shown promise in treating advanced or recurrent cases of uterine cancer, where conventional treatment methods often prove ineffective.

The specificity of targeted therapy allows for a more personalized treatment approach by targeting molecular or genetic abnormalities unique to a patient’s disease. This precision and focus on cancer-specific pathways also reduces the side effects experienced by the patient.

Furthermore, targeted therapy can be administered along with other treatment methods such as chemotherapy to further improve patient outcomes.

However, targeted therapy has its limitations. Targeted therapy requires a specific target such as a protein or mutation involved in cancer pathways. Developing a drug that specifically targets these structures or features remains a challenge.

Cancer cells may also develop resistance against targeted therapeutics. For instance, cancer cells may undergo mutations which allow them to grow and function normally even though the target has been blocked. Furthermore, as every patient’s cancer is made up of different genetic changes, the effectiveness of targeted therapy is heavily dependent on each individual patient’s cancer cells.

Like all cancer treatments, targeted therapy is also linked to its own distinct set of side effects. Commonly reported side effects include but are not limited to:

• Fever
• Nausea and vomiting
• High blood pressure
• Slowed wound healing
• Swelling
• Rashes
• Hair loss
• Skin and nail changes

Targeted therapy may also result in severe side effects, although they do not occur as frequently. These include:

• Internal bleeding or blood clots: angiogenesis inhibitors interfere with the normal growth and development of blood vessels. This may cause bleeding, bruising, blood clots or in severe cases, stroke and heart attack.
• Heart damage: targeted therapy may damage the heart, causing chest pain, difficulty breathing and dizziness.
• Allergic or infusion reactions: monoclonal antibodies are administered via IV infusions. These may result in allergic reactions such as hives, difficulty breathing and swelling.

It is crucial to be mindful of these side effects and notify your healthcare provider immediately should you experience any of them.