Health Scan: Pharmacological Trojan horse for fighting cancer

In In The News by Barbara Jacoby

Thumbnail for 7099By: Judy Siegel-Itzkovich


Some cancer cells are highly resistant to drugs. Now researchers at the Technion-Israel Institute of Technology have made a discovery to help fight this phenomenon, namely that drug-resistant cancer cells frequently produce a large number of lysosomes. These are membrane- bound structures found in animal cells whose enzymes are capable of breaking down virtually all kinds of biomolecules, including proteins, lipids (fats), nucleic acids, carbohydrates and cellular debris.

Taking advantage of this unique feature of the production of multiple lysosomes, and the dramatic, irreversible accumulation of certain lipid-soluble drugs bearing light-sensitive properties in these lysosomes, a “pharmacological Trojan horse” was developed that resulted in the destruction of the resistant cancer cells.

For this groundbreaking research achievement, biology faculty dean Prof. Yehuda Assaraf has been awarded the Hilda and Hershel Rich Innovation and Entrepreneurship Award. His innovative technology, which has been registered as a US patent, has aroused much interest among major international pharmaceutical companies.

Its potential as a therapeutic approach was published recently in the journal Cell Death and Disease.

“Cancer cells acquire a wide range of sophisticated mechanisms to overcome cytotoxic drug therapy [chemotherapy] directed against them,” explained Assaraf.

“This phenomenon, known as ‘multidrug resistance’ [MDR], often stems from the fact that cancer cells possess an abundance of pump proteins located in the membrane of cancer cells that act as efficient pumps to expel a multitude of anti-cancer drugs from the cancer cells. This is an important mechanism by which malignant tumors become resistant to chemotherapy.”

Two types of MDR are known – inherent drug resistance that exists prior to drug therapy, as well as acquired drug resistance, that is provoked by drug treatment.

Thus Assaraf and members of his research team, including Dr. Michal Stark, Dr. Eran Bram and Yamit Adar, made it their primary goal to develop innovative therapeutic strategies to overcome the MDR phenomenon, which is a major hindrance to the development of drug therapies for cancer.

The researchers searched for the Achilles’ heel of MDR cancer cells, and discovered that MDR cancer cells often contain a large number of microscopic intracellular organelles called lysosomes.

Lysosomes were first discovered in 1974 by Nobel Laureate Prof. Christian de Duve. They break down to safeguard the proper physiological functioning of body cells.

The researchers discovered that light-sensitive, lipid-soluble drugs bearing weak basic features selectively concentrate, at very high levels, within the multiple lysosomes present in MDR cancer cells.

“When we illuminated the MDR cells containing the light-sensitive drugs trapped in the lysosomes, it created oxygen-free radicals that destroyed the lysosome membrane and as a result, all of the contents of the lysosomes were spilled into the cancerous cell. This resulted in a massive release of the above enzymes, and rapid digestion and destruction of MDR cancer cells,” said Asseraf.

In a multinational study using multidrug resistant tumors of human ovarian cancer origin, the core of the tumor was destroyed upon exposure to light, and blood vessels feeding the tumor were destroyed or blocked. As a result, the blood supply to the remaining cells in the malignant tumor was cut off, and this led to the destruction of any malignant cells that remained.

Still, a practical treatment for malignant tumors is still a long way off. In the meantime, Asseraf and his team are working on the development of a second-generation “pharmaceutical Trojan horse” to selectively target cancer cells by homing in protein receptors present on the malignant cells without harming healthy body cells.