2024-12-04 09:51:00
AND Molecular ‘switch’ in bladder cancer, a mechanism that constitutes a biomarker in the evolution of this tumor. It is the finding that paves the way for new therapeutic strategies resulting from the study, conducted by the team of researchers from the European Institute of Oncology (Ieo) and the University of milan, published in Nature Communications.The research also demonstrates that superficial and deep bladder tumors represent different stages of a single pathological process that evolves over time, contrary to what was believed until now. The study supported by the Airc Foundation for cancer research was coordinated by Salvatore Pece, professor of General Pathology and vice-director of the Department of Oncology and Hemato-Oncology of the State University of Milan, director of the ‘Hormone-dependent tumors and IEO stem cell pathobiology.
The study
There seems to be the origin of the entire process to Numb proteinswhich is normally expressed in the bladder but is lost in over 40% of all human bladder tumors.This loss causes a cascade of molecular events that make the tumor highly proliferative and invasive, allowing it to go beyond the superficial layers of the bladder mucosa to reach the deeper layers. The event represents the turning point in the clinical evolution of the disease, determining the progression of superficial bladder tumors, the so-called non-muscle-invasive, towards deep tumors, defined as muscle-invasive, which require total surgical removal of the bladder . Despite the radical operation,these forms of the disease are characterized by an frequently enough unfavorable clinical course.
“So the Numb protein – explains Pece – It works like a molecular switch that,if turned off,accelerates tumor progression and influences the clinical course of the disease. It is a molecular biomarker that allows the identification of superficial tumors at high risk of progression to muscle-invasive tumors.Our discovery has a strong and immediate potential for request in clinical practice. The clinical-pathological criteria used routinely to predict the risk of progression of superficial bladder tumors to muscle-invasive tumors are in fact fully insufficient and inadequate to identify low-risk patients, who could benefit from more targeted, conservative treatments, in active surveillance protocols. High-risk patients rather require more aggressive treatments, such as chemotherapy and surgical removal of the bladder, which sadly have considerable side effects and a high impact on quality of life.”
“We analyzed the molecular profile both in cultured cells and laboratory animals, and in samples of human tumors lacking the expression of Numb,” explains francesco Tucci, PhD student at the European School of Molecular Medicine and first author of the study. “We have thus observed that lThe loss of Numb activates a complex molecular circuit that leads to the activation of a powerful oncogene, the transcription factor Yap. The latter is the basis of the proliferative and invasive power of tumor cells“.
“Bladder tumors without numb – continues Tosoni – are thus very aggressive but also highly vulnerable”. They are indeed some molecular drugs used in the clinic for pathologies other than bladder cancer are already available, which could quickly be tested and adopted as innovative treatments to prevent the clinical progression of high-risk superficial bladder tumors, lacking the Numb protein. “At the time of initial diagnosis – explains Pece – the vast majority of bladder tumors present themselves as non-muscle invasive superficial tumors, which are generally characterized by a good prognosis. Only in a small percentage do they present themselves as tumors from the outset deep muscle-invasive, very aggressive and with a less favorable clinical course”.Approximately “20-30% of superficial tumors can evolve into muscle-invasive tumors. Clinical experience has taught us that muscle-invasive tumors resulting from the progression of initially superficial tumors represent the most aggressive and perhaps lethal forms of bladder cancer “.
“Our studies – continues Pece – now demonstrate that superficial and deep bladder tumors represent different stages of a single pathological process that evolves over time, guided from the beginning by specific molecular mechanisms that can be hindered with precise and targeted drugs. It therefore becomes essential to identify the biological mechanisms underlying this evolution and develop new molecular markers to identify patients with specific aggressive characteristics.
In this context,our discovery opens the way to new therapeutic strategies to fight bladder cancer in a high percentage of patients with tumors lacking expression of the Numb protein. We have also identified – concludes Pece – a new molecular signature that will allow us to identify with accurate precision the patients who will be able to benefit from targeted treatments with new drugs that specifically target the molecular mechanisms that are activated following the loss of Numb”.
how could the findings on Numb protein impact future bladder cancer treatments?
Interviewer: Welcome to Time.news,where we explore the latest in science and medicine. Today, we’re delighted to have with us Professor Salvatore Pece, a leading researcher from the European Institute of oncology, who has been pivotal in discovering a new molecular mechanism related to bladder cancer. Professor Pece, thank you for joining us.
Professor pece: Thank you for having me! I’m excited to discuss our findings and their implications for bladder cancer treatment.
Interviewer: Your recent study published in Nature Communications has shed light on the role of the Numb protein in bladder cancer progression. Can you elaborate on why this protein is so notable?
Professor pece: Certainly! The Numb protein acts as a sort of molecular switch in bladder cells. Normally, it helps regulate cell differentiation and maintains the balance between cell growth and death. However,in over 40% of bladder tumors,we observed a loss of the Numb protein. This loss triggers a series of molecular events that promote the tumor’s proliferation and invasiveness, allowing it to progress from non-muscle-invasive to muscle-invasive forms of the disease.
interviewer: That’s engaging but also alarming. So, this loss seems to play a pivotal role in the advancement of the disease?
professor Pece: Exactly.When the Numb protein is lost, the cancer becomes more aggressive and can penetrate deeper layers of the bladder, ultimately leading to a more severe clinical course. This is crucial as it fundamentally changes how we view bladder tumors; they stage the evolution of a single pathological process rather than being seen as entirely different entities, as previously thought.
Interviewer: this new understanding must have profound implications for treatment strategies. Can you share how your findings could influence future therapeutic approaches for bladder cancer?
Professor Pece: Absolutely. By recognizing that superficial and deep tumors are connected in their progression, we can focus on developing treatments that target the mechanisms related to Numb expression. If we can find ways to restore or mimic the function of Numb in these tumors, we may be able to halt their progression before they become muscle-invasive.
Interviewer: It sounds like there’s real potential for breakthrough therapies. What are the next steps in your research?
Professor Pece: We plan to further investigate how the loss of Numb protein alters the molecular pathways involved in bladder cancer. Our goal is to identify specific targets for drug advancement. We are also collaborating with clinicians to translate our findings into clinical applications seamlessly.
Interviewer: Collaboration seems key to this research. How important are partnerships in the scientific community, especially in tackling cancer?
Professor Pece: Very important! Cancer is a complex disease, and no single lab can tackle it alone. Collaborations allow us to combine expertise and resources, accelerating discoveries and transforming them into viable treatments.Support from institutions like the AIRC Foundation for Cancer Research has also been instrumental for our work.
Interviewer: Lastly, Professor Pece, what message would you like to convey to patients and their families who are navigating bladder cancer?
Professor Pece: It’s important to remain hopeful. The field of cancer research is advancing rapidly, and discoveries like ours are contributing to more precise and effective treatments. Patients should stay informed about the latest research and consider discussing clinical trials with their healthcare providers, as they may offer access to emerging therapies.
Interviewer: Thank you, Professor Pece, for this enlightening discussion and for your dedication to advancing our understanding of bladder cancer.
Professor Pece: Thank you for the opportunity to share our work!
