World Cancer Research Day
Lung cancer remains the leading cause of cancer deaths worldwide, and while new therapies are helping some patients live longer, drug resistance continues to be one of the biggest obstacles in treatment. A recent study sheds light on this challenge by focusing on a new experimental drug called RX-3117, a type of medicine known as a nucleoside analog, such as gemcitabine, which is currently used to treat patients. These drugs work by disrupting how cancer cells copy their DNA, which is essential for their growth.
This research wanted to understand why some lung cancer cells eventually stop responding to therapy. To do this, experiments were performed to look deep inside resistant cancer cells and compare them to cells that remained sensitive to the drug. These studies discovered that resistance was linked to changes in DNA repair systems and cell cycle control—the biological “checkpoints” that decide when cells grow and divide. In resistant cells, these pathways had adapted to bypass the drugs effects.
One particularly important finding involved a protein called PKMYT1, which helps regulate the cell cycle. By blocking PKMYT1, resistant lung cancer cells were made sensitive to RX-3117 again. This suggests that combining RX-3117 with drugs targeting PKMYT1, or related pathways, might be an effective strategy for overcoming resistance.
Why does this matter? Because drug resistance is one of the most frustrating realities for patients and doctors alike. A treatment that works well at first may lose its power over time, forcing patients to move on to less effective or more toxic options. Understanding resistance at the molecular level is the first step toward designing smarter, longer-lasting therapies.
This study is also a strong example of how academic research can drive progress in cancer treatment. Even though RX-3117 and inhibitors of PKMYT1 are still under investigation, insights from the lab can inform the design of future clinical trials, not only for this drug but also for similar therapies.
As we mark World Cancer Research Day, this research highlights the global importance of studying not just how to treat cancer, but how to stay one step ahead of the disease’s ability to fight back. Every discovery about resistance mechanisms brings us closer to developing therapies that remain effective longer, offering patients more hope and better quality of life.
MD, PhD. received her M.D. and Ph.D. with full marks and from the University of Pisa, Italy, in 2000 and 2007, respectively. Between 2001 and 2004, she contributed to translational studies on pharmacogenetics as clinical fellow in Pharmacology in the Department of Oncology of Pisa University.
Since 2006 she collaborated with the Department of Medical Oncology at VU University, Amsterdam, The Netherlands, to set-up a line of research on (epi)genetic determinants of drug activity and molecular mechanisms underlying chemoresistance in pancreatic and lung cancer. Her current research interests include also the role of liquid biopsies in prediction of drug activity/resistance.
She was promoted to Associate Professor in 2016, received the habilitation as Full Professor in 2022, and she is also working as PI of a Start-Up lab at the Fondazione Pisana per la Scienza, Pisa, Italy. She has supervised 16 completed PhD students and is currently supervising 16 PhD students and 2 postdoctoral researchers.
She is actively involved, as past-chair, in research projects within the “Pharmacology and Molecular Mechanism Group” group of the EORTC (EORTC-PAMM), as well as in the European Pancreatic Club and Dutch and Italian associations for the study of the pancreas (DPCG, AISP, I-PCC).
She successfully requested funding from the Netherlands Organization for Scientific Research (NWO, VENI grant), Horizon-MSCA, FP7 and COST European Initiatives, Italian Association for Research against Cancer (AIRC, Start-Up and IG grants), Cancer Center Amsterdam (CCA) Foundation, and Dutch Cancer Society (KWF).
Dr. Giovannetti is author or co-author of >400 scientific publications in peer reviewed journals, with an H-index of 76 (Google Scholar), she has been invited for >200 Selected/Invited Lectures in international meetings, seminars and webinars and she is Deputy Editor of Critical Reviews in Oncology and Hematology, Associate Editor of Journal of Experimental and Clinical Cancer Research, Cancer Chemotherapy and Pharmacology, Cellular Oncology, and Journal of Chemotherapy.