Angela Cappello, PhD, received a 2024 KCA Trailblazer Award for research on “Drugs resistance mechanisms guided by amino acids catabolism in clear cell renal cell carcinoma (ccRCC).” Dr. Capello is part of the Interdisciplinary Department of Medicine at the University of Bari “Aldo Moro” in Bari, Italy. We spoke with her about her research and the impact it could have on people with kidney cancer.
What is your project about and how did you develop the idea?
This study is looking at how the loss of AUH, a protein involved in the catabolism of the amino-acid Leucine, could impact on clear cell renal cell carcinoma (ccRCC) metabolism, and increase its aggressiveness. Indeed, cancer cells usually have a strong metabolic reshaping which allows them to overcome the continuous resources need to grow, to get to other sites of the body and to evade the immune system control and other therapeutic treatments (such as anti-angiogenic drugs). Using different molecular/cellular approaches and preclinical mice models, we will find specific weak points in the cancer cells’ metabolism that can be exploited as therapeutic targets.
In my previous work experience I had the opportunity to study, at a metabolic level, the processes of proliferation and differentiation that are the basis of the development of a normal epithelium. In this new experience with my mentor Professor Camillo Porta, I would like to conjugate my interest in basic research on metabolism with clinical needs in ccRCC to understand how metabolic changes in cancer cells could impact on tumor response to normal therapies.
What about your research could be most exciting for patients and families?
This research aims to improve the understanding of how kidney cancer cells grow and can become resistant to treatments and of consequence to disseminate to other sites of the human body. We hope to discover new ways to make existing treatments more effective or to develop entirely new therapies. This could lead to better outcomes, fewer relapses, and potentially more personalized treatment options for patients. If our preclinical results are promising the future goal of our work would be finding markers that could predict how well a treatment might work for a single patient, helping doctors choose the best approach for each person. For patients and their families, this means a step toward more targeted and successful cancer care.
What is the understanding of kidney cancer like in Italy and other parts of Europe and how does your project contribute to this knowledge?
The understanding of kidney cancer among doctors and researchers in Italy and Europe is quite advanced, and many international efforts in identifying genetic and molecular mechanisms that drive the disease have been carried out in some healthcare centers all along the country. My mentor, Dr. Camillo Porta, is one of the most experienced medical oncologists worldwide in the treatment of kidney cancer, but, to date, many questions, particularly regarding the metabolic changes in kidney cancer cells, drug resistance, and how to tailor treatments to individual patients, still have no answer. We hope that my project will contribute to this knowledge focusing on an underexplored aspect of kidney cancer: the metabolic reshaping and its impact on treatment resistance dependent on a specific enzyme involved in amino acid catabolism. By investigating the connection between this enzyme, amino acids metabolism, and therapy outcomes, we aim to uncover new vulnerabilities in kidney cancer cells that could be targeted with innovative treatments. This could enhance the current understanding of kidney cancer not only in Italy but also across Europe, promoting more effective and personalized therapeutic strategies.
What motivates you?
It seems obvious but I started to study Biology and then Cellular and Molecular Biology (of which I am madly in love with) because I believe that research (even basic) is fundamental to help people. Since I started my journey, I never thought that my choice, was wrong. I have sacrificed and still sacrifice my Saturdays and Sundays to take small steps that can help research in the fight against cancer. Knowing that, with my small contribution, I hope I will do something that (maybe) can help developing a cure for a cancer patient. I firmly believe that these motivations belong to altruistic people who believe in science and who, even if they are not medical graduates and therefore in direct contact with the patient, hope to be just as useful. I hope one day to find the same selfless principles in the little man I’m growing up and I hope he is proud of his mother, who doesn’t stop fighting for what she believes in. I am confident that this award can help me acquire new skills in the study of cancer, to independently carry out an important project, which may subsequently open prospects for preclinical research regarding metabolic changes and/or the tumor therapy resistance.
What else do you want others to know about you or your research?
We want others to know that we hope our pre-clinical data can make a difference in the choice of treatment and improve patient life expectancy increasing our understanding of kidney cancer.
Our work is deeply rooted in collaboration and innovation, combining advanced laboratory techniques like 3D tumor models, metabolomics, and CRISPR-Cas9 gene editing with bioinformatics to uncover new insights. We are committed to translating these findings into practical applications that can improve treatment options and outcomes for patients with kidney cancer.
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- Source: https://www.kidneycancer.org/stories/grants-angela-cappello/