Abstract 3103: Perspectives of novel tissue engineering technologies for next generation cancer therapeutics

Abstract Cancer is the second leading cause of death in the United States, behind cardiovascular disease. For the first time, new cancer cases in the US will exceed 2 million in 2024 while 611, 720 cancer deaths are projected for 2024. Further, the global economic burden of cancer is estimated to reach $25.2 trillion by 2050. Cancer metastases are responsible for 90% of the deaths due to cancer. While the discovery of new biomarkers for early detection, also enhanced by recent efforts in machine learning for image diagnostics, of various cancers, such as breast cancer, has improved mortality rates; therapeutics in the event of metastasis are limited. Further, in vivo, experiments for metastasis are primarily limited by the need for intracardiac injections to initiate metastasis and the use of immunocompromised animals. Tissue engineering, the holy grail of regenerative medicine, presents an innovative technology in the cancer metastasis arena. Besides providing a novel means for reconstruction surgeries, tissue engineering technologies enable the development of robust and reliable in vitro models of metastasis that present new tools to evaluate cancer pathophysiology to assess specific cancer phenomena such as adhesion to metastatic site and migration of cells and cell clusters. We demonstrate here current emerging technologies that are expected to greatly impact the mortality of patients with metastasis. These include two specific developments in the tissue-engineered in vitro models. These include the development of an accurate tumor microenvironment and the development of fluid-flow-enabled systems that exert physiologically relevant shear stresses on the cancer cells and tumors. While 5, 541 articles (as reported by the National Library of Medicine) illustrate various in vitro models of cancer metastases developed using tissue engineering, only 58 report the concurrent use of flow characteristics in conjunction with the development of accurate tumor microenvironment, and 45 of those just in the past decade. The role of fluid flow-derived shear stresses during extravasation and tissue invasion are key factors that initiate and propagate the metastasis cascade. We present a state-of-the-art analysis of current tissue engineering technologies that are at the forefront in the development of tumor models of breast, prostate, colon, and pancreatic cancer metastases as a tool for screening therapeutic agents. Micro-engineered tumor environments enabled using microfluidics cancer-on-a-chip also offer advantages of a concurrent tumor microenvironment mimicry in combination with fluid-based cancer transport, which resulted in 213 publications with 185 in the last decade. The concurrent gene and protein analysis enabled via fluid flow-based bioreactors with tissue-engineered scaffolds makes this a promising technology, and it is expected to test new therapies that will help reduce the large cancer burden. Citation Format: Preeya D. Katti. Perspectives of novel tissue engineering technologies for next generation cancer therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3103.