Israeli and Italian Scientists Identify Cancer Cell Weaknesses, Leading to New Treatment Possibilities

In a significant breakthrough, Israeli and Italian scientists have identified crucial vulnerabilities in cancer cells that could lead to innovative treatments. Researchers from Tel Aviv University and the European Institute of Oncology in Milan uncovered specific weaknesses in aneuploid cells cancer cells with an abnormal number of chromosomes in two recent studies.

Aneuploidy, a condition where cells deviate from the normal 23 pairs of chromosomes, is a common feature in many cancers. These abnormalities create unique stressors on cancer cells, which the researchers believe can be targeted for more effective treatments.

The studies, led by Professor Uri Ben-David and doctoral student Johanna Zerbib in Tel Aviv, alongside Professor Stefano Santaguida and doctoral student Marica Rosaria Ippolito in Milan, found two major weaknesses in aneuploid cells: their reliance on DNA repair mechanisms and their struggle to manage excess protein production. These findings were published in Cancer Discovery and Nature Communications.

“A significant portion of cancer cells are aneuploid, and this trait distinguishes them from healthy cells,” explained Ben-David. “Our work focuses on the vulnerabilities of aneuploid cells, with the aim of promoting new strategies for eliminating cancerous tumors.”

Building on previous research, the team induced aneuploidy in genetically identical human cell cultures, allowing them to isolate the specific effects of abnormal chromosome counts. Through DNA and RNA sequencing, protein level measurements, and CRISPR screening, they identified that the MAPK (mitogen-activated protein kinase) pathway plays a key role in DNA repair in aneuploid cells.

Their research showed that disrupting the MAPK pathway made these cancer cells more sensitive to chemotherapy, which works by causing DNA damage. This discovery could enable doctors to treat cancer with lower doses of chemotherapy, reducing harmful side effects.

Another significant vulnerability identified was the overproduction of RNA and proteins in aneuploid cells, a result of their abnormal chromosome numbers. The cells attempt to degrade this excess material, making them particularly sensitive to drugs that inhibit protein degradation. The researchers found that aneuploid cells are more susceptible to such drugs, potentially paving the way for repurposing existing treatments to target highly aneuploid cancers.

This groundbreaking research offers new hope for more effective, targeted cancer therapies by exploiting the specific weaknesses of aneuploid cancer cells.

Stay updated on the latest medical innovations by subscribing to our newsletter.