Results may help identify patients for novel treatments to halt the growth of cancerous cells
A new study by molecular biologists at NUI Galway has uncovered genetic differences which could be used to identify patients who would benefit from drugs which stop the growth of cancerous cells.
The research team from the University’s Centre for Chromosome Biology has been studying the molecular response of cells to a drug that blocks the first step of DNA replication.
The research paper, published in the prestigious journal Cell Reports, states that its findings can be applied to help develop novel cancer treatments.
When both normal and cancer cells divide their DNA needs to be replicated, so that both mother and daughter cells get a complete copy of the DNA.
CDC7 is a protein that is needed at an early stage in the process of DNA replication and new drugs that block the action of CDC7 are being developed as anti-cancer therapeutics. But they can also impact the growth of normal cells.
Previous research from Professor Corrado Santocanale’s team at the Centre for Chromosome Biology in NUI Galway showed that CDC7 targeting drugs can kill cancer cells while temporarily blocking the growth of normal cells.
Dr Michael Rainey, honorary research lecturer at the Centre for Chromosome Biology and the main contributor to the study, said: “These drugs are likely to have significantly less of the toxic side effects associated with other chemotherapeutic drugs that kill both normal and cancer cells.
“But now our research has given us two other key findings on CDC7 targeting drugs and their impact on cells.
“We have uncovered a molecular pathway which influences whether cells either stop growing or die when treated with CDC7 targeting drugs. Even more importantly, we identified a number of genes that are required for the cell growth block – and if these genes are mutated cells can actually grow in the presence of the drugs.”
Professor Santocanale and Dr Rainey say these findings pave the way for the identification of cancer patients who may benefit from CDC7 targeting drugs. It would also help to identify those patients who would not respond to treatment with these drugs and can instead be redirected to alternative treatments.
Dr Rainey added: “Using sophisticated molecular genetic technologies we have screened all human genes and found a number of genes that are critical for the cells to stop growth in the presence of CDC7 targeting drugs. Excitingly this work has also helped us to understand how cells coordinate the process of DNA replication and the partitioning of DNA into mother and daughter cells.”
Professor Santocanale, Professor of Molecular Medicine at the Centre for Chromosome Biology and Discipline of Biochemistry in the School of Natural Sciences at NUI Galway, added: “Many novel drugs are being developed worldwide to fight cancers. However, because cancers are very different at the molecular level, not all patients respond to treatment in a similar manner. So, for each new drug, the big challenge is to identify the molecular signature that allows us to predict whether a tumour will respond to treatment or fail treatment.
“Major advancements and investments in genomics technology have been pivotal in increasing our molecular understanding of how cells copy the genetic information and in understanding how CDC7 targeting drugs work, which is essential to maximise their therapeutic potential.”
This study is published in the prestigious journal Cell Reports and is available at https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31085-8