Old Drug with Potential to Revolutionise Cancer Treatment

Researchers at The Ohio State University Comprehensive Cancer Center have found that papaverine,  a drug that has been used as a muscle relaxant since 1848, could make radiation therapy more effective.

Background

Cancer is the uncontrolled growth of abnormal cells in the body. The disease develops when the body’s normal control mechanism stops working; old cells do not die and instead grow out of control, forming new, abnormal cells. These extra cells may form a mass of tissue, called a tumour. Some cancers, such as leukemia, do not form tumours. Treatment options depend on the type of cancer, its stage if cancer has spread and the patients general health. The goal of treatment is to kill as many cancerous cells while reducing damage to normal cells nearby, and the three main methods of doing this are surgery, chemotherapy and radiation therapy. Surgery works by directly removing the tumour, chemotherapy uses chemicals to kill cancer cells, and radiation uses x-rays to kill cancer cells.

Analysis

A muscle-relaxant first discovered in 1848 might make radiation therapy more effective, according to a study by The Ohio State University Comprehensive Cancer Center. Radiation is the most common treatment of cancer, targets tumours in two ways: firstly, it damages DNA and, secondly, it produces oxygen radicals that also harm cancer cells. However, when oxygen levels are low (hypoxia), the body produces fewer oxygen radicals, meaning that radiation therapy is less effective. Because cancer cells divide so quickly, they require more oxygen than healthy tissue. At the same time, blood vessels within tumours are often poorly constructed, making them less efficient. This means that cancer cells often run out of oxygen, making radiation therapy less deadly to cancer. Similarly, these dead, hypoxic zones in the tissue, where blood supply is limited, are difficult for drugs carried in the blood to reach. In this way, hypoxia can reduce the impact of both radiation therapy and chemotherapy.

In their search for ways to improve radiation therapy, researchers at OSUCC, led by Dr Nicholas Denko, came across a drug called papaverine. Currently, papaverine has a variety of uses, none of which have direct links to cancer. For instance, papaverine has been used to reduce muscle spasms and to treat erectile dysfunction.

Papaverine works by inhibiting respiration in mitochondria, the powerhouse of the cell. Dr Denko and his team found that by blocking the activity of oxygen-consuming mitochondria, they could make tumours more sensitive to radiation therapy. They showed that one dose of papaverine before radiation therapy reduced mitochondrial activity, thereby limiting hypoxia and enhancing the destruction of tumour cells.

Earlier attempts to address the hypoxia problem have focused on adding more oxygen to a tumour. This study takes the opposite approach, by reducing the oxygen demand. Importantly, the drug did not make healthy tissue more sensitive to radiation therapy.

The researchers hope that by adjusting the structure of papaverine, they might be able to enhance its benefits further. By tinkering with its makeup, they might potentially reduce side effects, too. These findings were published recently in the Proceedings of the National Academy of Sciences.

Assessment

Our assessment is that although a great deal more work will be needed before this intervention comes into wider usage, it is an exciting finding. Because it is a relatively simple process, using a well-tested drug to boost the performance of existing cancer treatments, it is likely to make effective cancer treatment more accessible and affordable to many.