New avenues for cancer treatment emerge from an Italy-USA study authored by Scientists from the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University in Philadelphia, spearheaded by Antonio Giordano, and the National Cancer Institute of Naples Pascale Foundation. The study, featured in the journal 'Oncogene' (Nature group) and supervised by Luigi Alfano of the Pascale Foundation, elucidated a previously undisclosed function of the CDK9 protein, previously discovered by Giordano's team in 1994.
In cancer patients, Cdk9 expression is altered, and a specific 'variant' of it (isoform 55) spurs tumor growth. Using the Crispr/Cas9 molecular toolkit to eliminate CDK9 expression, the authors demonstrated that the absence of CDK9-55 inhibits a mechanism called homologous recombination. This mechanism, vital for repairing DNA damage, enables cancer cells to thrive and multiply. Basically, the absence of Cdk9, mutated in tumors, exposes cancer cells' susceptibility to chemotherapy treatments.
"We've already developed a new line of CDK9 inhibitors, which will complement existing ones and are yielding promising results in clinical settings," Giordano tells Adnkronos Salute.
Thus, the study sheds light on a novel role of Cdk9 in DNA repair regulation. "The role of normal CDK9 protein is safeguarding the cell's genome to prevent errors in the gene sequence" explains Alfano, the article's corresponding author. "CDK9 mutations in tumors could be therefore pivotal in escalating the mutational burden driving transformation and cancer progression".
"This discovery," Giordano,the head of the research project, comments "enables us to add a vital piece to the puzzle of understanding how cells select repair mechanisms, in order to prevent genetic integrity and the emergence of mutations, which can predispose to cancer. It's a significant breakthrough because elucidating CDK9's role, a gene our group discovered in 1994, sets the stage for developing novel pharmacological inhibitors. These inhibitors can be used both as single therapy or in combination with existing drugs to amplify their anti-tumor efficacy. Moreover, this discovery lays the groundwork for further investigations for assessing CDK9 as a potential novel predictive factor of response to pharmacological treatments targeting DNA repair.
Professor Antonio Giordano, M.D., Ph.D., is the creator and head of the Sbarro Health Research Organization, located at Temple University's College of Science and Technology in Philadelphia. Stay connected with him through his various social media platforms, including Facebook, LinkedIn, Twitter, and Instagram, to receive the latest updates.