Kidney Cancer: Combination of HDAC Inhibitor With IL-2

What Is Kidney Cancer?

As the name suggests, kidney cancer is a cancer of the kidneys. Cancer occurs when the cells present in the human body show uncontrolled growth and spread to nearby organs. Cancer might occur in any body organ, but when it originates from the kidneys, it is known as kidney cancer. In contrast, babies and young children are more likely to develop another type of kidney cancer known as Wilms tumor. Studies have reported that the incidence of kidney cancer has been increasing day by day. One of the reasons might be the availability of advanced imaging techniques like computed tomography (CT) scans. These imaging tests are done frequently and help diagnose kidney cancer. However, the good news is that kidney cancer is discovered early before it spreads to the surrounding organs.

What Are the Risk Factors for Kidney Cancer?

Doctors are unaware of the exact causes of kidney cancer but have discovered certain factors that increase the risk of kidney cancer. For example, patients above 40 years are more likely to suffer from kidney cancer. The other risk factors for kidney cancer are listed below:

1. Smokers are more likely to experience kidney cancer compared to non-smokers.

2. Males are at a higher risk of kidney cancer than females.

3. Obesity or excess weight might cause hormonal changes and increase the risk of kidney cancer.

4. Using over-the-counter drugs or other drugs without a prescription also increases the chances of kidney cancer.

5. Patients having advanced kidney diseases and on dialysis for a prolonged period are more likely to experience kidney cancer.

6. Having a family history of kidney disease or kidney cancer is one of the risk factors.

7. Farmers and people working in chemical industries are exposed to harmful chemicals and are more likely to suffer from kidney cancer.

8. People having lymphoma and some genetic diseases are more likely to develop kidney cancer.

What Are Some of the Signs and Symptoms of Kidney Cancer?

In some cases, people might not have any symptoms of kidney cancer, but the symptoms appear when the tumor grows large. The following are the symptoms of kidney cancer:

• Hematuria (blood in the urine).

• A lump or swelling in the side of the abdomen.

• Loss of appetite.

• Flank pain that does not subside easily.

• Weight loss for unknown reasons.

• Fever for more than two weeks.

• Tiredness.

• Anemia.

• Swelling in the legs and ankles.

If cancer spreads to the surrounding organs, the following symptoms appear:

• Shortness of breath.

• Chest pain.

• Pain in the bones.

• Blood discharge while coughing.

What Are HDAC Inhibitors?

HDAC inhibitors or histone deacetylase inhibitors are new drugs used to treat kidney cancer. They work against factors that induce death and arrest cell growth in cancer. Vorinostat and Depsipeptide are the two HDAC inhibitors recently approved by the Food and Drug Administration (FDA) in the treatment of cancer. Several clinical trials are going to know about the use of other HDAC inhibitors. However, scientists have not fully understood the mechanism of action of HDAC inhibitors. Cancer does not always occur due to a defect in the genes. They might also occur due to the acetylation and deacetylation of the proteins present in the DNA (deoxyribonucleic acid). The body maintains a perfect balance between the acetylation and deacetylation of DNA proteins, but the problem arises when diseases like cancer disturb this balance. The HDAC inhibitors used in the treatment of kidney cancer are listed below:

• Vorinostat - It is one of the most advanced HDAC inhibitors approved by the FDA in 2006 to treat advanced forms of renal cancer. Vorinostat has proven to be effective in phase 1 and phase 2 clinical trials to treat hematological tumors and malignancies. It can be given orally with a maximum dose of 400 mg once daily or 200 mg twice daily for three consecutive days per week to treat advanced-stage renal cancer.

• Depsipeptide - It is a unique HDAC inhibitor prodrug that binds with zinc and shows its effect on the body. Nausea, vomiting, and fatigue are the common side effects of HDAC inhibitors.

What Is IL-2?

IL-2, or interleukin-2, is the only treatment capable of curing patients with renal cell carcinoma. The effects of IL-2 on renal cell carcinoma were first studied in 1985. As the IL-2 drugs showed complete response during the clinical trials, the FDA approved their use against renal cell carcinoma. Studies have reported that cancer subsided in most patients, and only a few patients showed recurrence of the disease. IL-2 inhibitors must be administered at an interval of eight hours according to the patient's tolerance. However, minimal side effects are seen if the patient is carefully monitored and fluid replacement therapy is provided on time. So IL-2 must be the first line of treatment for patients with kidney cancer.

Combination of HDAC Inhibitor With IL-2: What Has Been Known So Far?

Doctors have discovered that a combination of HDAC inhibitors and IL-2 might enhance their pharmacological actions and prove effective against kidney cancer. High-dose IL-2 has been considered more effective against metastatic kidney cancer than low-dose IL-2. During a clinical trial, it was discovered that this combination induces minimal toxicities in patients and is beneficial in treating kidney cancer. When a clinical trial was conducted on 255 patients, it was observed that IL-2 produced a response of 15 percent. During the study, it was also found that a combination of IL-2 and HDAC had a combined antitumor effect. However, during the studies, it was found that HDAC inhibitors are a double-edged sword because they are beneficial in treating cancer, but they might stimulate the immune response on the other hand.

Conclusion

A combination of HDAC inhibitors and IL-2 has opened new avenues of research in the treatment of kidney cancer. The effects of these drugs on cancer are still under research, but scientists have a clue that they reduce the growth of cancer cells. Kidney cancer has become a common condition these days, and the problem is people lose hope as soon as they are diagnosed with cancer. Nowadays, medical science has advanced so much that cancer is no longer an incurable condition. The imaging techniques like CT scans, magnetic resonance imaging (MRI), and ultrasound help diagnose kidney cancer without any delay. The most peculiar feature of kidney cancer is that it gets caught in the early stages before it damages other organs. So, the patient must not worry and consult a urologist to learn more about the treatment of kidney cancer.