Researchers at Tel Aviv University (TAU) have identified a new, highly selective targeted therapy that has the potential to effectively treat breast cancer and a wide range of other solid cancers in humans. The research, supported by a grant from the Israel Cancer Research Fund (ICRF), “is based on a small molecule called PJ-34 that is soluble in water and permeates the cell membrane,” explains lead investigator Prof. Malka Cohen-Armon, of TAU’s Sackler School of Medicine. “This molecule exclusively eradicates a variety of cancer cells without harming normal tissues.” Moreover, the more aggressively are cancer cells proliferating the more efficiently they are eradicated by PJ-34".
PJ-34 is a member of a family of drugs that inhibit poly ADP ribose polymerase 1 (PARP1), a protein involved in repairing damaged DNA. Originally developed more than 10 years ago to preserve nerve cells stressed by a stroke or inflammation, the drugs were found inappropriate for their intended use and were released solely for research purposes. Cohen-Armon and her team began studying how the compound acts within the nucleus of cells in hope of discovering an application for DNA repair.
When PJ-34 was injected into female mice transplanted with the incurable triple negative breast-cancer, the investigators discovered that PJ-34 stopped tumor growth and prevented the development of new tumors. In tissue cultures, PJ-34 prevented cell division and eradicated cancerous cells, while normal cells continued to proliferate (e.g., increasing in number as a result of cell division) .
“We found that PJ-34 and other similar molecules 'turn on' a mechanism specific to human solid cancer cells that causes them to die during cell division without harming normal tissue,” explains Cohen-Armon. “The more rapidly the cancer cells are proliferating the more efficiently they are eradicated by PJ-34” says Cohen-Armon, who believes she and her colleagues have found “an Achilles heel of human solid cancer cell.”
“As soon as you can target cancerous cells without killing healthy ones you can produce efficient medications that would cause a lot less suffering to the patient,” she explained in a recent newspaper interview. “We can even give a much more aggressive treatment without worrying about harming healthy tissues.” Some 233,000 women and 2,400 men will be newly diagnosed with breast cancer in the United States in 2014 and more than 40,000 people will die of the disease, according to the American Cancer Society.
In ongoing research supported by ICRF, Cohen-Armon and her team are working to decipher the molecular mechanisms responsible for the anti-cancer effects of PJ-34. “If we can understand the molecular mechanism and identify the targets of PJ-34, it will open a new mode of therapy for a variety of cancer types", she explains. “We have tested PJ-34 in tissue cultures of aggressive human cancers derived from patients' tumors, including pancreas and non-small lung cancers, glioblastoma, ovary and colon cancers. The encouraging results urge us to develop PJ-34 and its derivatives for cancer therapy without side effects.”
ICRF is a nationwide charitable organization founded in 1975 by a group of American and Canadian researchers, oncologists, and lay people. It is the largest U.S.-based charity solely devoted to supporting cancer research in Israel and receives its total income from private donations.