A Way to Increase the Effectiveness of Radiotherapy Found

A muscle relaxant synthesized back in 1848 may become a modern drug against cancer. This refers to the well-known medical drug papaverine, which, as researchers from the Interdisciplinary Oncology Center at Ohio State University have proven, can significantly enhance the effectiveness of radiation therapy by making malignant tumor cells more sensitive to ionizing radiation.

Among the effective methods for combating cancer available in modern oncology, one of the most commonly used is radiotherapy. It is based on the ability of oxygen radicals, which are formed under the influence of ionizing radiation, to destroy DNA and other important structures of tumor cells, leading to their death. However, at insufficient levels of oxygen in the body — a condition known as hypoxia, or oxygen starvation — fewer oxygen-containing radicals are produced, which in turn reduces the effectiveness of radiation therapy.

Since malignant cells divide very quickly, they require more oxygen than healthy cells. At the same time, the network of blood vessels within the tumor is poorly developed, which does not allow it to maintain adequate oxygen levels. This leads to the fact that often cancer cells experience a lack of O2, which affects the effectiveness of radiation therapy.

Similarly, conglomerates of dead cells due to hypoxia form necrotic zones within the tumor tissue, hindering the access of drugs introduced into the bloodstream — as a result, they simply do not reach their target. Thus, hypoxia reduces the effectiveness of not only radiation therapy but also chemotherapy.

Can Hypoxia Be Overcome?

Author of the recent study, Dr. Nicholas Denko, explains why oxygen starvation of cells is such a significant obstacle in the fight against cancer: "We know that a lack of O2 in tumor tissues limits the therapeutic possibilities of radiation therapy, and this is a serious problem, as more than half of cancer patients undergo radiation therapy at some stage of treatment."

"If the pathological cells that remain in the necrotic areas of the tumor mass survive after exposure to ionizing radiation," continues the doctor, "they can subsequently cause a relapse. Therefore, it is critically important for us to find a way to overcome this form of therapeutic resistance."

In search of a solution to the problem of low effectiveness of radiation therapy, Dr. Denko and his team stumbled upon a drug called papaverine. Nowadays, it has wide applications but has never been used in cancer patients. Papaverine is usually prescribed to combat muscle spasms and sexual dysfunction.

The action of the drug involves suppressing the respiratory process in mitochondria, tiny organelles that are called the energy stations of the cell. The research group led by Dr. Denko discovered that by blocking the active consumption of oxygen by the mitochondria, it is possible to increase the sensitivity of tumors to ionizing radiation. They proved that taking a small dose of papaverine before the start of irradiation reduces mitochondrial activity, thereby combating oxygen starvation and helping to destroy cancer cells.

Previous attempts to solve this problem focused on increasing the level of oxygen in tumor cells. The new study, however, offers a radically different approach based on reducing the O2 consumption by cells. Importantly, the sensitivity of healthy tissues to radiation therapy remains unchanged after the use of papaverine.

What’s Next?

The results of the study were published in the leading American scientific journal Proceedings of the National Academy of Sciences. In an extensive commentary on the publication, the scientists noted: "The fact that cells with a lack of oxygen are two to three times more resistant to radiation therapy than cells that do not experience oxygen starvation is a well-known and proven fact. Our study may become an important milestone in the decades-long attempts by scientists to find a way to cope with hypoxia, which is the main reason for the low effectiveness of radiation treatment."

However, this discovery is not the end of the matter. Researchers hope that by altering the structure of papaverine, they will be able to enhance its action in the future. By updating its component composition, they could also potentially reduce the side effects of the drug.

Despite the fact that much effort and a series of trials will be needed before the new approach is widely applied, the results of the American scientists' research look promising. Especially since the method they propose is remarkably simple — to use a well-known and proven drug to enhance the effectiveness of already existing anti-cancer methods.