scholarly journals A microfluidic platform for functional testing of cancer drugs on intact tumor slices

Lab on a Chip ◽  
2020 ◽  
Vol 20 (9) ◽  
pp. 1658-1675 ◽  
Author(s):  
A. D. Rodriguez ◽  
L. F. Horowitz ◽  
K. Castro ◽  
H. Kenerson ◽  
N. Bhattacharjee ◽  
...  
Keyword(s):  
Drug Testing ◽  
Functional Testing ◽  
Cancer Drugs ◽  
Microfluidic Platform

We have developed a digitally-manufacturable microfluidic platform that allows for multiplexed drug testing of intact tumor slices.

scholarly journals A Microfluidic Platform for Functional Testing of Cancer Drugs on Intact Tumor Slices

2020 ◽  
Author(s):  
A.D Rodriguez ◽  
L.F Horowitz ◽  
K. Castro ◽  
H. Kenerson ◽  
N. Bhattacharjee ◽  
...  
Keyword(s):  
Drug Testing ◽  
Porous Membrane ◽  
Patient Specific ◽  
Precision Oncology ◽  
Functional Testing ◽  
Cancer Treatments ◽  
Microfluidic Platform ◽  
Promising Tool ◽  
Solvent Bonding ◽  
Response Testing

AbstractPresent approaches to assess cancer treatments are often inaccurate, costly, and/or cumbersome. Functional testing platforms that use live tumor cells are a promising tool both for drug development and for identifying the optimal therapy for a given patient, i.e. precision oncology. However, current methods that utilize patient-derived cells from dissociated tissue typically lack the microenvironment of the tumor tissue and/or cannot inform on a timescale rapid enough to guide decisions for patient-specific therapy. We have developed a microfluidic platform that allows for multiplexed drug testing of intact tumor slices cultured on a porous membrane. The device is digitally-manufactured in a biocompatible thermoplastic by laser-cutting and solvent bonding. Here we describe the fabrication process in detail, we characterize the fluidic performance of the device, and demonstrate on-device drug-response testing with tumor slices from xenografts and from a patient colorectal tumor.

scholarly journals A microfluidic platform for cultivating ovarian cancer spheroids and testing their responses to chemotherapies

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Neda Dadgar ◽  
Alan M. Gonzalez-Suarez ◽  
Pouria Fattahi ◽  
Xiaonan Hou ◽  
John S. Weroha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Drug Testing ◽  
Microfluidic Devices ◽  
Needle Aspiration ◽  
High Concentration ◽  
Microfluidic Platform ◽  
Drug Concentrations

Abstract There is increasing interest in utilizing in vitro cultures as patient avatars to develop personalized treatment for cancer. Typical cultures utilize Matrigel-coated plates and media to promote the proliferation of cancer cells as spheroids or tumor explants. However, standard culture conditions operate in large volumes and require a high concentration of cancer cells to initiate this process. Other limitations include variability in the ability to successfully establish a stable line and inconsistency in the dimensions of these microcancers for in vivo drug response measurements. This paper explored the utility of microfluidics in the cultivation of cancer cell spheroids. Six patient-derived xenograft (PDX) tumors of high-grade serous ovarian cancer were used as the source material to demonstrate that viability and epithelial marker expression in the microfluidic cultures was superior to that of Matrigel or large volume 3D cultures. To further demonstrate the potential for miniaturization and multiplexing, we fabricated multichamber microfluidic devices with integrated microvalves to enable serial seeding of several chambers followed by parallel testing of several drug concentrations. These valve-enabled microfluidic devices permitted the formation of spheroids and testing of seven drug concentrations with as few as 100,000 cancer cells per device. Overall, we demonstrate the feasibility of maintaining difficul-to-culture primary cancer cells and testing drugs in a microfluidic device. This microfluidic platform may be ideal for drug testing and personalized therapy when tumor material is limited, such as following the acquisition of biopsy specimens obtained by fine-needle aspiration.

scholarly journals Multiplexed drug testing of tumor slices using a microfluidic platform

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
L. F. Horowitz ◽  
A. D. Rodriguez ◽  
Z. Dereli-Korkut ◽  
R. Lin ◽  
K. Castro ◽  
...  
Keyword(s):  
Drug Testing ◽  
Microfluidic Platform

scholarly journals Multiplexed drug testing of tumor slices using a microfluidic platform

2020 ◽  
Author(s):  
L. F. Horowitz ◽  
A.D. Rodriguez ◽  
Z. Dereli-Korkut ◽  
R. Lin ◽  
K. Castro ◽  
...  
Keyword(s):  
Small Molecules ◽  
Drug Testing ◽  
Drug Response ◽  
Cancer Drug ◽  
Cancer Tissue ◽  
Human Glioma ◽  
Microfluidic Platform ◽  
Tissue Microenvironment ◽  
Tumor Biopsies ◽  
Individual Human

ABSTRACTCurrent methods to assess the drug response of individual human cancers are often inaccurate, costly, or slow. Functional approaches that rapidly and directly assess the response of patient cancer tissue to drugs or small molecules offer a promising way to improve drug testing, and have the potential to identify the best therapy for individual patients. We developed a digitally-manufactured microfluidic platform for multiplexed drug testing of intact cancer slice cultures, and demonstrate the use of this platform to evaluate drug responses in slice cultures from human glioma xenografts and patient tumor biopsies. This approach retains much of the tissue microenvironment and can provide results rapidly enough, within days of surgery, to guide the choice of effective initial therapies. Our results establish a useful preclinical platform for cancer drug testing and development with the potential to improve cancer personalized medicine.

scholarly journals Microdissected “cuboids” for microfluidic drug testing of intact tissues

Lab on a Chip ◽  
2021 ◽  
Vol 21 (1) ◽  
pp. 122-142
Author(s):  
Lisa F. Horowitz ◽  
Adan D. Rodriguez ◽  
Allan Au-Yeung ◽  
Kevin W. Bishop ◽  
Lindsey A. Barner ◽  
...  
Keyword(s):  
Drug Testing ◽  
Multiple Drug ◽  
Microfluidic Platform ◽  
Live Tissue

A microfluidic platform permits multiple drug testing of uniformly-sized microscale “cuboids” of live tissue with well-preserved microenvironments.

Predictive value of a CLIA-approved organoid based drug sensitivity test.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3630-3630
Author(s):  
Astrid Margossian ◽  
Annie Richardson ◽  
Michael Churchill ◽  
Franz Schaub ◽  
Rachele Rosati ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Drug Testing ◽  
Drug Sensitivity ◽  
Metastatic Cancer ◽  
Functional Testing ◽  
Genomic Biomarkers ◽  
Therapeutic Decisions ◽  
The Right

3630 Background: Precision medicine integrates genetic, molecular, and clinical information to optimize therapy selection for cancer patients. Ex vivo drug testing has the potential to match the right drug to the right patient. We developed a CLIA-certified functional drug assay for all solid tumors which provides an actionable report of organoid sensitivity to targeted, endocrine and chemotherapy agents as a tool for therapeutic decisions. Objectives: To establish the predictive power of the test in relation to well-known genomic biomarkers as well as prior treatments to identify drug sensitivity. To demonstrate that functional drug testing increases the actionability of genomic reports. Methods: From 2016 to 2019, 240 organoids from cancer patients were subjected to functional testing at SEngine Precision Medicine. Patients with advanced primary or metastatic cancer (solid tumors) who were treatment naïve or had previous therapies fail. Fresh samples of tumor cells from core biopsies, surgical excisions, or fluids arrived <48 hrs following collection and were cultured as 3D organoids. They were evaluated using a multi-dose response format with a library of up to 130 compounds. Drug sensitivity was quantified using a score that combines sensitivity and personalization of each patient’s response relative to a reference population. Known genomic actionability from levels of evidence 1-2 from MSKCC OncoKB were queried against results for correlation. Results: Organoids were derived from breast (18.7%), ovarian (18.3%), colorectal (17.9%), pancreatic (6.7%), and others solid tumors (38,3%). Median age of patients was 53 (r5-83). 68 drugs on average were tested per patient with a mean turnaround time of 18 days (r9 -37). A mean of 7 drugs per patient were identified as top scoring drugs. In 75 patients with genomic data, we found high concordance of drug sensitivity with known genomic anchors (e.g., inhibitors of BRCA1/ PARP, ERBB2/HER2, FGFR1-2/FGFR, KRAS, PIK3CA/PI3K), measured as sensitivity to drugs among this targeted groups. However, several patient samples demonstrated sensitivity to targeted agents in the absence of known genomic biomarkers. Most important, analysis of previous treatments indicated >90% of retrospective concordance. Conclusions: Organoid based drug testing exhibits strong concordance with genomic and retrospective clinical evidence. In addition, functional testing identifies candidate therapies in patients with no known biomarkers and can identify the significance of variants currently not validated.

scholarly journals Pumpless microfluidic platform for drug testing on human skin equivalents

Lab on a Chip ◽  
2015 ◽  
Vol 15 (3) ◽  
pp. 882-888 ◽  
Author(s):  
Hasan Erbil Abaci ◽  
Karl Gledhill ◽  
Zongyou Guo ◽  
Angela M. Christiano ◽  
Michael L. Shuler
Keyword(s):  
Human Skin ◽  
Drug Screening ◽  
Drug Testing ◽  
Microfluidic Platform ◽  
Skin Equivalents ◽  
Human Skin Models

Advances in bio-mimetic in vitro human skin models increase the efficiency of drug screening studies.

scholarly journals Integrated heart/cancer on a chip to reproduce the side effects of anti-cancer drugs in vitro

RSC Advances ◽  
2017 ◽  
Vol 7 (58) ◽  
pp. 36777-36786 ◽  
Author(s):  
Ken-ichiro Kamei ◽  
Yoshiki Kato ◽  
Yoshikazu Hirai ◽  
Shinji Ito ◽  
Junko Satoh ◽  
...  
Keyword(s):  
Side Effects ◽  
Cell Types ◽  
Cancer Drugs ◽  
Microfluidic Platform ◽  
Anti Cancer ◽  
Different Cell Types

Integrated Heart/Cancer on a Chip (iHCC) is a promising microfluidic platform that allows the culture of different cell types separately and application of closed-medium circulation to reproduce the side effects of doxorubicin on heart in vitro.

scholarly journals STRN-ALK rearranged pediatric malignant peritoneal mesothelioma – Functional testing of 527 cancer drugs in patient-derived cancer cells

2021 ◽  
Vol 14 (4) ◽  
pp. 101027
Author(s):  
Astrid Murumägi ◽  
Daniela Ungureanu ◽  
Mariliina Arjama ◽  
Ralf Bützow ◽  
Jouko Lohi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Peritoneal Mesothelioma ◽  
Functional Testing ◽  
Cancer Drugs ◽  
Malignant Peritoneal Mesothelioma

Drug testing in the patient: Toward personalized cancer treatment

2015 ◽  
Vol 7 (284) ◽  
pp. 284ps10-284ps10 ◽  
Author(s):  
R. Charles Coombes
Keyword(s):  
Clinical Practice ◽  
Drug Use ◽  
Adverse Effects ◽  
Cancer Treatment ◽  
Drug Testing ◽  
Cancer Drugs ◽  
Personalized Cancer

Two different devices show that delivery of cancer drugs directly into tumors in vivo can indicate cancer sensitivity; if implemented in clinical practice, these devices have the potential to reduce indiscriminate drug use, to improve survival, and to reduce unnecessary adverse effects (Jonas et al. and Klinghoffer et al., this issue).

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