Identified a new method to characterize ovarian tumors. Greater survival and lower risk of relapse would be linked to the level of chromosomal instability. Objective: to improve diagnosis for targeted therapies
The DNA of cancer cells is unstable. This characteristic can be identified with a low-depth genomics method, which looks at the chromosomes from above, without going into the detail of the single mutation. With this method, a group of Italian researchers found that the genome of ovarian tumors characterized by three different types of structural alterations that define a different prognosis, i.e. a different survival of patients with first stage ovarian cancer. According to the scientists, this information could improve the diagnosis and possibly the therapy of this cancer.
Chromosomal instability
Still considered one of the most difficult cancers to cure among gynecological cancers, ovarian cancer affects about 5,200 women every year in Italy alone, with 3 thousand deaths in 2020 alone. Often the diagnosis is late because the disease does not cause specific symptoms in the early stages. The results obtained in the study highlighted an important biological feature of ovarian cancer: chromosomal instability – he explains Maurizio D’Incalci, coordinator of the works, head of the laboratory of anti-tumor Pharmacology of Humanitas and professor of Humanitas University -. Not all cases are equal: there are cases with highly unstable chromosomes, cases with moderately unstable chromosomes and cases with stable chromosomes. The latter have a more favorable prognosis and have a low probability of relapse. The research focused mainly on the cases of early stage ovarian cancer, but these three types of chromosomal alterations have also been found in advanced cases, which affects most patients. it is likely that these structural alterations are a feature common to all stages. If this is confirmed, in the future the different chromosomal instability could be used as a new molecular classification modality ovarian tumors.
First stage neoplasm
Why improve knowledge of early stage disease? Due to the lack of specific symptoms in the early stages of the disease, it is particularly difficult to study early stage ovarian cancer. This makes it a relatively rare disease (20% of cases found). The molecular characterization study conducted by Humanitas researchers is the largest that has ever been published in the specialized medical literature on the first stage and was possible through the collaboration of many centers. Studying an early stage tumor is important for grasping the initial alterations which are essential for the development of the disease – he explains Sergio Marchini, another coordinator of the research team and head of the Molecular Pharmacology Laboratory and of the Genomics Unit of Humanitas -. This knowledge can provide us with elements to develop new diagnostic methods and therapeutic applications. Molecular characterization of the early stages of tumor growth it can, in fact, highlight whether there are any targets that we can hit to obtain a specific anticancer effect.
The clinical implications of the discovery
Knowledge of the chromosomal instability of each case, combined with histopathological and clinical data, can improve the definition of the risk of recurrence and therefore contribute to a more precise therapeutic choice for each patient. If the risk of recurrence is very low, it can be assumed that the patient is probably cured with only surgical therapy and therefore does not need additional chemotherapy, with a certain improvement in the quality of life – says Marchini-. If the risk is vice versa high, it is necessary intensify therapies.
Future developments
In addition to making the methods developed for molecular characterization available to the oncological scientific community, the Humanitas team is applying the knowledge obtained to develop a system that allows you to monitor the plasma (liquid biopsy) of patients with ovarian cancer. The ultimate aim is to understand if in plasma, with this system, they can identify the same molecular alterations found in the tumor, in order to define the risk of recurrence. Starting from the knowledge generated in this work – concludes D’Incalci -, we are working on the development of a novel method for the early detection of ovarian cancer. The challenge is very big, but the preliminary data we have obtained is extremely promising. The results, published in theEuropean Journal of Cancer
, emerged in a study supported by the Alessandra Bono Onlus Foundation and the AIRC Foundation for cancer research. The research was conducted on 205 patients with early stage ovarian cancer, thanks to the collaboration with various clinical and research centers in Italy (and beyond)including the San Gerardo Hospital of Monza, the Sant’Anna Hospital and the University of Turin, the Department of Biology of the University of Padua, the Mario Negri IRCCS Pharmacological Research Institute, the Department of Health Sciences, Genetics Medica, of the University of Milan, the IRCCS Ca ‘Granda Foundation Ospedale Maggiore Policlinico of Milan and the Cancer Research UK Cambridge Research Institute, University of Cambridge.
July 19, 2022 (change July 19, 2022 | 17:22)
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