A Novel Human Multi-Tissue System For Preclinical Drug Evaluation And Recapitulation Of Metastasis
By: Alan Chramiec
Publisher: [publisher not identified]
Published: 2022
Place of publication: [New York, N.Y.?]
Language: eng
Description: The drug development process, especially for anti-cancer therapies, continues to be highly inefficient. The current preclinical drug evaluation paradigm of human monolayer in vitro culture followed by small animal in vivo models results in a roughly 90% failure rate in clinical trials involving actual cancer patients. Our hypothesis then, is that there is a clear need for engineered, 3D, healthy and tumor tissue models capable of recapitulating patient physiology and disease, allowing for more accurate preclinical evaluation of anti-cancer drugs. Our hope, is that tissue engineering can provide us with valuable new insights into drug responses, over what we can currently achieve with existing models. Here, we present a new multi-tissue organs-on-a-chip microfluidic platform, Inter-Organ, designed to allow more comprehensive recapitulation of the disease seen in patients. We developed bioengineered tissues of primary and metastatic tumors across three cancer types, and integrated them into the Inter-Organ platform alongside healthy tissues like cardiac muscle known to cause failures in clinical trials for off-target drug toxicities.

Overall, the development of these new cancer models and their culture in the Inter-Organ platform allowed us to more accurately predict the success of various drugs in clinical trials than existing models could. Finally, this tissue engineering approach allowed us to explore the relationships between specific constituents of the tumor microenvironment, recapitulate complex cancer processes like metastasis previously only done in small animal models, and identify new potential diagnostic and therapeutic targets.
Notes: Department: Cellular, Molecular and Biomedical Studies.

Thesis advisor: Gordana Vunjak-Novakovic.

Thesis (Ph.D.)--Columbia University, 2022.