Radiation therapy kills cancer cells mostly by shattering their DNA. Photons of radiation pound the DNA, breaking it into small pieces, scrambling the tumor cells’ code of life and killing them.

Eric Radany, left, and Xufeng Chen explore methods to make tumors more sensitive to radiation therapy. (Photo by p.cunningham)

Now, City of Hope scientists may have found a way to make cancer’s DNA more vulnerable to therapeutic radiation’s powerful rays.

Department of Radiation Oncology researchers Xufeng Chen, M.D., staff scientist, and Eric Radany, M.D., Ph.D., clinical associate professor, led a team studying the effects of low doses of a drug called valproic acid on prostate cancer cells.

Valproic acid belongs to a group of drugs called histone deacetylase, or HDAC, inhibitors.

In recent years, cancer researchers have explored the anticancer effects of these drugs. They’ve found that HDAC inhibitors loosen coils of DNA in cancer cells, which should make the DNA more open and vulnerable to radiation therapy.

But the City of Hope scientists wondered if there was more to the story. Working in the lab, they were surprised to find that valproic acid boosted the effects of an important protein in the body that suppresses cancer growth.

The protein, called p53, mainly resides in the cell’s control center, the nucleus. It stifles cancer by driving tumor cells to kill themselves through a process called apoptosis.

Cells overproduce p53 when their genes become damaged, such as when they’re hit by therapeutic radiation. But some cancer cells have mutations in p53 that weaken the protein and keep it from fighting cancer, so the tumor cells grow unhampered.

The team found that valproic acid helps p53 do its job, but in an unexpected way — it stabilizes a different type of p53 that works through the cells’ mitochondria.

Mitochondria are the tiny compartments in cells that generate energy. Valproic acid helps the p53 in mitochondria drive cancer cells to die.

The knowledge opens up new possibilities for anticancer drug targets, according to the researchers.

As they continue their work, they hope to identify other drugs that boost radiation therapy and other ways p53 and similar proteins may increase cancer cells’ sensitivity to therapeutic radiation.

They aim to find out if their strategy works in other cancer cell types, as well.