# Anti-Cancer Drug Screening with Microfluidic Technology
## 5 Limitations of Current Microfluidic Platforms for Drug Screening
\begin{table}
\begin{tabular}{c c c c} \hline \hline \multicolumn{4}{c}{**Monodrug Screening on a Microscale Sample**} \\ \hline
**Sample Type** & **Tested Drugs** & **Number of Combinations Tested** & **Ref.** \\ \hline \multirow{4}{*}{Ovarian cancer cells (SKOV-3)} & Methotrexate, adriamycin hydrochloride, BCNU, tamoxifen, thalidomide, celecoxib, actinomycin D, streptavidin, mitomycin, and ellipticine & 165 & \multirow{4}{*}{[62]} \\  & Doxorubicin, nilotinib, olaparib, capsaicin, tamoxifen, cisplatin, and tretition & & 210 & \multirow{4}{*}{[63]} \\  & & tamoxifen, cisplatin, and tretition & & 210 & \multirow{4}{*}{[62]} \\  & & tamoxifen, cisplatin, and tretition & & (1 or 2 drugs) & \multirow{4}{*}{[63]} \\  & & & sextuple & \\ \hline Tumor cell lines (MCF-7 and HepG2) & Doxorubicin and cisplatin & 3 & & [65] \\ \hline
3D hydrogel aggregates of carcinoma cell (A549 and T24) co-cultured with human umbilical vein endothelial monolayer cells (HUVECs) & MK-2206, AZD-0530, A83–01, and CI-1033 & 12 & & [66] \\ \hline
3D spheroids from glioblastoma multiforme (GBM) brain cancer (U87) cells & Pitavastatin and irinotecanin & 8 & [67] \\ \hline \multirow{3}{*}{Sphereoids of pancreatic cancer cell lines (MIA PaCa-2) and patient-derived xenograft cells} & 7 drugs: cisplatin, docetaxel, doxorubicin, gemcitabine, irinotecan, oxaliplatin, and 5-FU & 28 & [68] \\ \hline Cell lines and patient-derived CTC clusters of breast cancer & Doxorubicin and aspirin & 8 & [69] \\ \hline Thin-gel 3D cell-culture from MDA-MB-231 and MCF-7 breast cancer cell lines & Doxorubicin and paclitaxel & 64 & [70] \\ \hline
3D cell structures from a cancer cell line (MDA-MB-231) grown into aggregates, pancreatic tumor, organoids from patient-derived samples, and colon organoids from human-derived normal colon tissue samples & Gemcitabine, paclitaxel, fluorouracil (5-FU), docetaxel, CPT11, oxiplatin, and cisplatin & 5 combinatorial for 3 patients & [57] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: \(Cont.\)plicate the platform and decrease its user-friendly level, thus inhibiting its acceptance in clinical settings. Another important challenge of in-vitro microfluidic platforms is the accurate study of the absorption, distribution, metabolism, and excretion, commonly known as pharmacokinetics. To this aim, the effect of a drug on various organs, including the lungs, liver, kidneys, and gut, should be studied simultaneously. In the context of anti-cancer drug screening, multi-organs-on-a-chip platforms should be coupled with tumor-on-a-chip ones to better study the pharmacokinetics and related side effects of the drug. As such, a combination of these platforms with concentration gradient generators for high-throughput multi-drug screening can open new avenues in this field. In the context of personalized medicine, the microfluidic devices should be compatible with patient-derived samples. According to the limitation of current microfluidic platforms, there is a lack of combinatorial drug screening on macroscale samples, e.g., a patient's tissue sample obtained through surgical biopsy. A continuous gradient is generated on a macroscale sample in a few of the current microfluidic devices. In this way, the recent microfluidic device developed by [PERSON] et al. [76], with the capability of delivering two different reagents simultaneously on a microdissected tissue sample, is a promising platform as shown in Figure 4. Utilizing the presented microfluidic device, continuous linear gradients of two reagents could be generated along with the two different directions on a millimeter-sized sample (sample length and width). So, all possible combinations of two drugs would be distributed on the sample surface. Future works could focus on drug screening on the cancer tissue samples loaded in this microfluidic device.