Did you know that kidney cancer is among the top ten most common cancers in the UK and the USA? Kidney cancer is a very dangerous disease which usually arises in patients who are 60-70 years of age, often leading to kidney failure and complications in other organs if the diagnosis is made late.1
In this article, we will explore the characteristics of kidney cancer, as well as the different treatments available, highlighting the use of targeted therapy.
Kidneys are significant organs in the body with multiple functions, including detoxifying blood and eliminating waste from the body. When there is an abnormal growth of cells in the kidney, it leads to the formation of a mass or tumour. These can be benign or malignant. Kidney cancer is predominant in men when compared to women and has a mortality rate of 30-40%. The main risk factors contributing to kidney cancer are smoking, obesity, and hypertension (high blood pressure).1
There are different types of kidney cancer. The most common one is renal cell carcinoma (RCC), making up almost 9 out of 10 cases in adults. It is further subdivided into 14 types, and the major ones are clear cell renal cell carcinoma (CCRCC), papillary renal cell carcinoma (PRCC), chromophobe renal cell carcinoma (ChRCC), and collecting duct renal cell carcinoma. RCC is one of the most lethal urologic cancers (affecting the urinary tract), with a five-year survival rate of 75%. Though RCC is the most common type of kidney cancer, other types include:2
Treatment of kidney cancer depends on the stage and condition of the disease at the time of diagnosis. The different forms of treatment can be:1, 2
When the cancer is advanced or has spread to other organs, the treatment may not be successful with the above options. In such instances, targeted therapy is used.
Targeted therapy involves targeting the proteins that control cancer cell growth, proliferation, and survival. The treatment usually involves either small-molecule drugs or monoclonal antibodies that attack the cancer cells either by killing them or preventing their growth. This is different from traditional chemotherapy, which kills all cells that grow and divide quickly.
Biomarker testing is needed to determine whether you need targeted therapy. Targeted therapy may be given in the form of a pill, as a shot, or intravenously (IV). The frequency of the treatment can vary depending on each situation, from once a week to several times a week or every day. Sometimes, targeted therapy is combined with other therapies, such as immunotherapy or radiation therapy. The advantages of targeted therapy are increased precision, fewer side effects, and improved outcomes.
Angiogenesis is the formation of new blood vessels, involving the growth, differentiation, and migration of endothelial cells that make up the lining of your blood vessels. It is controlled by a signalling protein called vascular endothelial growth factor (VEGF), which, upon binding to receptors on the cells, leads to the growth and survival of new blood vessels. In kidney cancer, solid tumours need a blood supply to grow in size. When this is interrupted by angiogenesis inhibitors, their growth and survival diminish, leading to a reduction in cancer proliferation. Some common angiogenesis inhibitors used in kidney cancer treatment are Sunitinib, Axitinib, Dovitinib, Sorafenib, and Pazopanib.3
Mammalian target of rapamycin (mTOR) is a protein kinase with many cellular functions, including cell division and survival. In cancer cells, abnormal mTOR leads to proliferation and spread to new healthy tissues. mTOR inhibitors are molecules that block the function of mTOR proteins by stopping the binding of the accessory protein to mTOR. This prevents cell division and the spread of the cancer cells. First-generation mTOR inhibitors, called rapamycin and rapalogs, are used for treating renal cell carcinoma. They include FDA-approved Temsirolimus and Everolimus. One of the recent reviews indicated that Everolimus is superior to Temsirolimus in metastatic renal cell carcinoma patients.4
Tyrosine kinase is an important enzyme involved in cell growth, differentiation, and signalling. In cancer cells, they are often found at higher levels. Tyrosine kinase inhibitors block the action of these enzymes, preventing cancer cells from growing. These may be reversible or irreversible inhibitors. The reversible inhibitors are further classified into 5 types, and each one has a different mechanism of action. FDA has approved more than 50 tyrosine kinase inhibitors to date, and some of the commonly used inhibitors in renal cell carcinoma are Sunitinib, Cabozantinib, and Lenvatinib.5
Immune checkpoints are pathways in our immune system that ensure an immune response does not destroy our healthy cells. But sometimes, in cancer cells, these checkpoints are stimulated, which protects them from immune response, so they can keep growing. Immune checkpoint inhibitors block the checkpoint proteins from binding to their respective partners, thereby signalling the immune system to kill the cancer cells. These inhibitors are part of immunotherapy but are often used with targeted therapy. Inhibitors, such as anti-CTLA-4 and anti-PD-1/PD-L1, are used to treat renal cell carcinoma. A recent study indicated that novel molecules such as LAG-3, TIM-3, and TIGIT are being used for renal cell carcinoma treatment in clinical trials.6
Your healthcare practitioner can help you decide which treatment would be best for you. They will consider several factors from your general health and symptoms, to the cancer stage and even minute details, such as the type of cells affected, to let you know if targeted therapy is the right choice.
Yes, targeted therapy can have limitations when the cancer cells become resistant to the therapy, and it does not work as expected. In some cases, drugs for certain targets are hard to develop depending on their structure and function.
The doctor will decide the duration of targeted therapy. It will depend on the drugs used and your condition. It generally takes a few weeks to months.
Yes. Like any other treatment, targeted therapy has side effects. Some of the common side effects are fatigue, diarrhoea, hypertension, dry skin, and skin rashes.
During the treatment, you will have regular visits to your doctor. The doctor will follow up on your condition with physical exams and other medical tests, such as scans and blood tests. These procedures will give an idea of how far the therapy is working.
Yes, targeted therapy can be done with other therapies, such as immunotherapy. There are reports on better outcomes with combined therapies.
Yes, targeted therapy is expensive. The cost depends on the drug molecules prescribed and the duration, again with the type and stage of cancer involved. Make sure to check with your insurance provider. Sometimes, medicines are available at a lower cost if you are part of a clinical trial or through a compassionate access program.
Pregnant women are generally advised not to undergo targeted therapy, as much research has not been done in this area. Monoclonal antibodies and other drugs have the potential to cause congenital abnormalities in the baby.
Kidney cancer is one of the top ten most common cancers worldwide. It is usually treated through radiation therapy, surgery, and ablation. However, targeted therapy is employed in advanced or metastatic cancers. Targeted therapy aims to eliminate the cancer cells in particular, with minimal damage to healthy cells. Several types of targeted therapies exist, including angiogenesis inhibitors, mTOR inhibitors, tyrosine kinase inhibitors, and immune checkpoint inhibitors. When combined with other therapies, such as immunotherapy, targeted therapy demonstrates promising outcomes and improved survival rates for kidney cancer patients. Ongoing research and clinical trials continually refine these treatments, offering increasing hope for effective management and improved quality of life.
