Scientists at the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology of the European Institute of Oncology in Milan have revealed how to eliminate cancer stem cells, the true reason for cancer’s incurability. Researchers led by Pier Giuseppe Pelicci, Director of the Department of Experimental Oncology of the European Institute of Oncology, and Professor of general pathology at the University of Milan, have discovered how cancer stem cells become immortal.
The same oncogenes that are responsible for triggering the process of tumor formation, also impede stem cells from growing old, and allow them to maintain their ability to form new tumor tissue. Basically, early cancer ‘mother’ cells replicate slower than other cells giving them time to repair damage making them virtually immortal. This discovery was published in Nature magazine.
“Current drugs”, a note from the oncologists that worked on the project explained, “are directed at later cancer cells, the ‘daughter cell’. This discovery paves the way for a phase of cures aimed at hitting original cancer stem cells or the mother cells”. New drugs with this function are already in the clinical testing phase on human beings: “In the next 5-10 years these drugs could become available for some types of tumors”. The study was performed in collaboration with the University of Milan.
“We already know that differently from stem cells found in normal tissue which age and die, cancer stem cells are immortal and indefinitely maintain their ability to preserve themselves and generate tumor cells”. But, explained Pelicci, “we did not know why”. “How do cancer stem cells avoid the physiological process of aging and death and indefinitely feed the tumor?” asked the researcher who solved the problem.
The team discovered that “the same genes responsible for one specific type of tumor, acute myeloid leukemia in this case, are also the direct cause of stem cell immortality. This was a completely unexpected effect, because it was known that human cells defend themselves from oncogenes activating a premature aging process called senescence, or by activating programmed cell death, known as apoptosis“. But this defense mechanism, observed the researchers, does not activate in the stem cells. “The stem cells survive and the oncogenes continue to function”.
“Normal stem cells in our tissues”, said Andrea, one of the authors of the discovery, “accumulate damage to their genome, stop functioning, and die. In the case of cancer stem cells, oncogenes make them immortal, increasing their ability to repair damage to their genome. In this way leukemia stem cells do not age and continue to indefinitely feed the leukemia”.
Scientists discovered that oncogenes facilitate repairs to the genome, and therefore the immortality of the stem cells, activating gene p21. This slows the multiplication of stem cells, leaving them more time to repair the damaged genome.
Essentially, leukemia stem cells do not age because they multiply very little. Extraordinarily, when Pelicci’s team removed gene p21 from the leukemia, the stem cells began to proliferate, accumulating damages, dying, and killing off the leukemia. These results provide a new model for tumors. Tumors formed by rare stem cells, which reproduce very little, and their many daughter cells, as we already know, are able to multiply rapidly.
“All of this” said the Italian researchers, “has important implications for tumor treatments: current anti-tumor therapies mainly target proliferating cells and are not efficient in fighting cancer stem cells. It is necessary to find new therapies that target stem cells, and their path is marked”.
“Our discovery”, commented Pelicci, “defines a method to eliminate cancer stem cells by blocking their system to repair the genome. In this way cancer stem cells will accumulate damage to their genome, age, and die, like normal stem cells in our tissues. New drugs that inhibit genome repair are making their first step toward clinical experimentation in humans. We will know in the next 5-10 years how important they are in tumor therapies”.
The study was performed at European Institute of Oncology labs in collaboration with the University of Milan (department of biomolecular science and biotechnology and the department of medicine, surgery, and dental surgery) and the University of Perugia (department of clinical medicine and experimentation, Monteluce general hospital), and was made possible thanks to financing from the Italian association for Cancer Research (AIRC), the Health Minister, the Cariplo Foundation, and the European Union.