Page 12 - ebook
P. 12
[A. Biochemistry/Molecular Biology] A-6
Cancer patient tissueoid with self-homing nano-targeting of
metabolic inhibitor
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Hyo-Jin Yoon¹ , Young Shin Chung² , Yong Jae Lee²#, Seung Eun Yu¹, Sewoom Baek¹, Hye-Seon Kim¹,
Sang Wun Kim², Yu-jin Nam¹, Jung-Yun Lee²*, Sunghoon Kim²*, Hak-Joon Sung²*
¹Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Korea, ²Department of
Obstetrics and Gynecology, Institution of Women’s Life Medical Science, Yonsei University College of Medicine,
Seoul 03722, Korea
The current paradigm of cancer medicine focuses on patient- and/or cancer-specific treatments, which has led to
continuous progress in the development of patient representatives (e.g., organoids) and cancer-targeting carriers
for drug screening. As breakthrough concepts, i) living cancer tissues convey intact profiles of patient-specific
microenvironmental signatures. ii) The growth mechanisms of cancer mass with intense cell-cell interactions can be
harnessed to develop self-homing nano-targeting by using cancer cell-derived nanovesicles(CaNVs). Hence, we
developed a tissueoid model of ovarian cancer (OC) by culturing OC patient tissues in a 3D gel chip, whose
microchannel networks enable perfusion to maintain the tissue viability. A novel model of systemic cancer responses
was approached by xenografting OC tissueoids into ischaemic hindlimbs in nude mice. CaNVs were produced to
carry general chemotherapeutics or new drugs under pre/clinical studies that target the BRCA mutation or energy
metabolism, thereby increasing the test scope. This pioneer study cross-validates drug responses from the OC clinic,
tissueoid, and animal model by demonstrating the alignment of results in drug type specific efficiency, BRCA
mutation-dependent drug efficiency, and metabolism inhibition based anti-cancer effects. Hence, this study provides
a directional foundation to accelerate the discovery of patient-specific drugs with CaNV application towards future
precision medicine.
