Has anyone survived stage 4 ovarian cancer
CT45 - a key to long-term ovarian cancer survival
Ovarian cancer is a highly aggressive disease. Only one in six patients survives more than 10 years, while the majority of patients die within the first two years of diagnosis. One of the main reasons for this is the late detection of the disease, because this usually only happens when the initial tumor, which has grown unnoticed, has spread from the ovaries to the surrounding organs.
By default, the cancer is then surgically removed as much as possible, followed by platinum-based chemotherapy. "Although this leads to an immediate improvement in the majority of patients, the therapeutic effects of the therapy are seldom permanent," explains Prof. Ernst Lengyel from the University of Chicago, one of the world's leading gynecological oncologists.
Scientists from the Max Planck Institute (MPI) for Biochemistry in Martinsried near Munich, together with researchers from Chicago and Copenhagen, have now investigated the molecular basis for long-term patient survival.
"Only when we understand the molecular causes and the differences between patients who respond well or poorly to therapy will we improve the treatment of ovarian cancer in the clinic and also pave the way for more personalized treatment options in the future," explains Lengyel. who initiated the study together with Prof. Matthias Mann, a pioneer and leading scientist in the field of mass spectrometric proteomics. Mann is director at the MPI for Biochemistry and head of the department "Proteomics and Signal Transduction".
The DNA in our cells is the building code for proteins - molecular machines that are the main actors in most biological processes. These include, for example, proteins for metabolism or cellular signaling. In recent years, Mann and his team have developed and refined mass spectrometry technology for protein analysis for clinical use.
"With mass spectrometry, we can for the first time identify almost all proteins, the proteome, in the patient's tumor tissue," says Mann. "Our highly sensitive methods now make it possible to analyze thousands of proteins at the same time and use the tissue samples to search for the proteins that are critical for the disease".
For their analysis, the researchers used by Prof. Lengyel and his team archived biobank material from the University of Chicago that had been collected over many years, most of which came from the patient's first operation.
"That way, in a sense, we can look back into the past because we know exactly how the patient reacted to chemotherapy," says Dr. Fabian Coscia, first author of the study and former PhD student with Matthias Mann and now a postdoctoral fellow in Copenhagen. Using mass spectroscopic analysis, the researchers discovered a largely unknown protein called CT45, which was greatly increased in long-term survivors. Subsequent tests in the laboratory confirmed the CT45 findings. If cancer cells were given the CT45 protein without CT45, the cells died much faster during chemotherapy.
But why does the cancer produce the protein CT45 when it promotes its own killing after chemotherapy? "The simple answer to this is that the cancer does not yet know that it is being treated with platinum-based chemotherapy," explains Coscia.
This gives hope for the development of new and more targeted therapeutic approaches. "We have evidence that tumor-specific expression of CT45 stimulates the patient's immune system to fight the cancer, as would a virus or bacterially infected cell. Our long-term goal is to build on these exciting new findings to find new ways to improve treatment outcomes ", summarizes Prof. Lengyel.
MEDICA.de; Source: Max Planck Institute (MPI) for Biochemistry in Martinsried near Munich
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