Table 1.

Potential targets identified and modeled using cancer‐on‐a‐chip (CoC) platforms.

Cancer modeled	Cell culture	Potential targets	Reference
Breast ductal carcinoma (BDC)	MCF7 microtissues co‐cultured with normal fibroblast microtissues or cancer‐associated fibroblast (CAF) microtissues	–Platelet‐derived growth factor (PDGF) receptors –Hyaluronic acid (HA) –Spaces of fibronectin and collagen network	[251]
BDC [two mutation models: ErbB2‐amplified and PI3KαH1047R]	MCF10A co‐cultured with primary human dermal micro‐ vascular cells (hMVECs)	–Human epidermal growth factor receptor (HER‐2) receptors –ErbB2 gene pathway –PI3KαH1047R gene pathway –Vascular endothelial growth factor (VEGF) receptor 2 –Interleukin‐6 (IL‐6)	[82]
HER2+ BDC	HER2+ BT474 co‐cultured with HUVEC and with or without Hs578T CAFs and peripheral blood mononuclear cells (PBMC)	–HER2 receptors	[81]
Adenocarcinoma BDC	MCF7 or MDA‐MB‐231 co‐cultured with or without HUVEC cells.	–Epidermal growh factor receptor (EGFR)	[89]
Glioblastoma	U87 human glioblastoma astrocytoma spheroids	–Vimentin –Matrix metalloproteinase‐2 (MMP‐2)	[94]
Glioblastoma	‐ U87MG human glioblastoma astrocytoma cells co‐cultured with HUVEC. ‐ Patient‐derived glioblastoma cells were cultured in GBM‐cell bioink, vascular‐cell bioink, and silicone ink, and then three dimensionally (3D) printed.	–Hypoxia (trigger) –Cell cycle checkpoint‐related gene	[234]
Glioblastoma	Patient‐derived glioblastoma tissue cultured to form spheroids.	–Hypoxia	[91]
Non‐small cell lung cancer (NSCLC), (adenocarcinoma)	Lung small airway chip: ‐ H1975 human NSCLC adenocarcinoma co‐cultured with primary human small airway epithelial cells and primary human lung microvascular endothelial cells. Lung alveolus chip: ‐ H1975 human NSCLC adenocarcinoma co‐cultured with primary human alveolar epithelial cells and human lung microvascular endothelial cells.	–EGFR –VEGF –IL‐6 –IL‐8 –Mesenchymal‐epithelial transition factor (c‐MET)	[208]
Lung Adenocarcinoma	A549 cancer cells co‐cultured with human amniotic membrane mesenchymal stem cells (hAM‐MSCs) to form 3D spheroids.	–Antigen Kiel 67 (Ki‐67)	[93]
Colorectal cancer	HCT116 colon cancer cells co‐cultured with human colonic microvascular endothelial cells (HCoMECs)	–Ki‐67 –MMP‐1 –Caspase‐3	[227]
Pancreatic ductal adenocarcinoma (PDAC)	Human S2‐028 PDAC cancer cells monoculture.	–Multi‐drug resistant proteins (MRPs)	[70]
PDAC	Two genotypes derived from genetically engineered murine pancreatic cells: KPC2 cells (with Kras and Trp53 mutations) and KIC cells (with Kras mutation and Cdkn2a deletion). The KIC cells used were of two phenotypes: epithelial (eKIC) and mesenchymal (mKIC). Five culture conditions were applied: monocultures of KPC2, eKIC, and mKIC, KPC2 co‐cultured with mKIC, and mKIC co‐cultured with eKIC.	–E‐cadherin –MMP‐9 –Fibronectin –Type IV collagen	[282]
B‐cell acute lymphoblastic leukemia (B‐ALL)	Three main culture conditions were employed: B‐ALL cells, niche cells, and B‐ALL cells co‐cultured with niche cells. Niche cells consisted of vascular endothelial (ECs), perivascular mesenchymal stem cells (MSCs), and endosteal osteoblasts. ‐ B‐ALL cells of different genotypes were used, including murine (Ph+ GFP+), human (EVT6‐RUNX1 REH, MLL RS(4;11), E2A‐PBX1 697, E2A‐HLF UOCB1, and NALM‐6, Ph+ SUP‐B15) and patient‐derived (Ph+ B‐ALL blasts and non‐Ph+ B‐ALL blasts) B‐ALL cells. ‐ Murine (C166) and human (HUVEC) epithelial cells ‐ Murine MSCs (OP9) and human BM stem cells hMSCs, cord blood cells (CD34+ cells), and BM mononuclear cells. ‐ Human osteoblast cells (hFOB 1.19).	–Chemokine ligand 5 (CCL5) –CCL2 –IL‐6 –IL‐8 –Ki‐67 –Nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) pathway –Stromal cell‐derived factor‐1 (CXCL12) and chemokine (C‐X‐C motif) receptor 4 (CXCR4) –Vascular cell adhesion molecule‐1 (VCAM‐1) /Very late antigen‐4 (VLA‐4)	[252]
Ovarian endometroid adenocarcinoma	A2870 epithelial ovarian cancer cells co‐cultured with human ovarian microvascular endothelial cells (HOMECs)	–Glycoprotein VI (GPVI) –galectin 3	[85]