Drug That Targets Scar-Like Tissue in Tumors Shows Promise for Aggressive Pancreatic Cancer

Pancreatic cancer is often diagnosed at an advanced stage, which means that chemotherapy is often the only treatment option available. Many pancreatic cancers develop chemotherapy resistance soon after treatment starts, which contributes to the poor survival of patients. Part of this resistance is driven by tumor fibrosis within and around pancreatic tumors that in turn reduces the effectiveness of chemotherapy drugs.

Findings from the Garvan Institute of Medical Research reveal a new Australian drug that targets scar-like ‘fibrotic’ tissue within tumors shows promise for treating pancreatic ductal adenocarcinoma, one of the most aggressive forms of pancreatic cancer with a five-year survival rate of less than 10%.

The research in mouse models showed that when given in combination with chemotherapy, the drug PXS-5505 increased survival time by more than 35%, compared to chemotherapy treatment alone.

The new drug PXS-5505, developed by Sydney-based pharmaceutical research company Pharmaxis (ASX: PXS) and currently in Phase II clinical trials for the treatment of bone marrow cancer, works by blocking a family of enzymes that are critical for the deposition of collagen into the fibrotic tissue around tumors.

“PXS-5505 returns the tumor microenvironment to a more ‘normal’ state by reducing fibrosis and decreasing tumor stiffness,” explains Dr Jessica Chitty, Senior Research Officer at Garvan and first author of the study. “This allows chemotherapy drugs to penetrate the tumors more easily, work more effectively, and destroy more cancer cells.”

“PXS-5505 shows real potential to improve chemotherapy for patients,” says Associate Professor Cox. “We are now in the process of progressing this work toward clinical trials that will evaluate this promising drug combination approach for pancreatic cancer patients.”


Sources: 

Jessica L. Chitty, Michelle Yam, Lara Perryman, Amelia L. Parker, Joanna N. Skhinas, Yordanos F. I. Setargew, Ellie T. Y. Mok, Emmi Tran, Rhiannon D. Grant, Sharissa L. Latham, Brooke A. Pereira, Shona C. Ritchie, Kendelle J. Murphy, Michael Trpceski, Alison D. Findlay, Pauline Melenec, Elysse C. Filipe, Audrey Nadalini, Sipiththa Velayuthar, Gretel Major, Kaitlin Wyllie, Michael Papanicolaou, Shivanjali Ratnaseelan, Phoebe A. Phillips, George Sharbeen, Janet Youkhana, Alice Russo, Antonia Blackwell, Jordan F. Hastings, Morghan C. Lucas, Cecilia R. Chambers, Daniel A. Reed, Janett Stoehr, Claire Vennin, Ruth Pidsley, Anaiis Zaratzian, Andrew M. Da Silva, Michael Tayao, Brett Charlton, David Herrmann, Max Nobis, Susan J. Clark, Andrew V. Biankin, Amber L. Johns, David R. Croucher, Adnan Nagrial, Anthony J. Gill, Sean M. Grimmond, Lorraine A. Chantrill, Angela Chou, Tanya Dwarte, Xanthe L. Metcalf, Gloria Jeong, Lara Kenyon, Nicola Waddell, John V. Pearson, Ann-Marie Patch, Katia Nones, Felicity Newell, Pamela Mukhopadhyay, Venkateswar Addala, Stephen Kazakoff, Oliver Holmes, Conrad Leonard, Scott Wood, Oliver Hofmann, Jaswinder S. Samra, Nick Pavlakis, Jennifer Arena, Hilda A. High, Ray Asghari, Neil D. Merrett, Amitabha Das, Peter H. Cosman, Kasim Ismail, Alina Stoita, David Williams, Allan Spigellman, Duncan McLeo, Judy Kirk, James G. Kench, Peter Grimison, Charbel Sandroussi, Annabel Goodwin, R. Scott Mead, Katherine Tucker, Lesley Andrews, Michael Texler, Cindy Forrest, Mo Ballal, David Fletcher, Maria Beilin, Kynan Feeney, Krishna Epari, Sanjay Mukhedkar, Nikolajs Zeps, Nan Q. Nguyen, Andrew R. Ruszkiewicz, Chris Worthley, John Chen, Mark E. Brooke-Smith, Virginia Papangelis, Andrew D. Clouston, Andrew P. Barbour, Thomas J. O’Rourke, Jonathan W. Fawcett, Kellee Slater, Michael Hatzifotis, Peter Hodgkinson, Mehrdad Nikfarjam, James R. Eshleman, Ralph H. Hruban, Christopher L. Wolfgang, Aldo Scarpa, Rita T. Lawlor, Vincenzo Corbo, Claudio Bassi, Nigel B. Jamieson, David K. Chang, Stephan B. Dreyer, Lea Abdulkhalek, Tatjana Schmitz, Victoria Lee, Kym Pham Stewart, Mehreen Arshi, Angela M. Steinmann, Marina Pajic, Paul Timpson, Wolfgang Jarolimek, Thomas R. Cox. A first-in-class pan-lysyl oxidase inhibitor impairs stromal remodeling and enhances gemcitabine response and survival in pancreatic cancer. Nature Cancer, 2023; DOI: 10.1038/s43018-023-00614-y

Garvan Institute of Medical Research. “Drug that targets scar-like tissue in tumors shows promise for aggressive pancreatic cancer.” ScienceDaily. ScienceDaily, 29 August 2023. <www.sciencedaily.com/releases/2023/08/230829125932.htm>.

Images from:

Photo by Laurynas Mereckas 

https://unsplash.com/photos/1TL8AoEDj_c