We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Noncancerous Cells of the Tumor Microenvironment Skew Drug Effectiveness Assays

By LabMedica International staff writers
Posted on 24 Mar 2010
Print article
Cancer researchers have developed a system for screening drug candidate compounds that is based on cancer cells that are "co-cultured” with noncancerous cells in a format that mimics the natural tumor microenvironment.

Conventional anticancer drug screening is typically performed in the absence of noncancerous cells of the tumor microenvironment, which can profoundly alter antitumor drug activity. To address this limitation, investigators at the Dana-Farber Cancer Institute (Cambridge, MA, USA) developed a tumor cell-specific in vitro bioluminescence imaging (CS-BLI) assay. In this assay system tumor cells (for example, myeloma, leukemia, and solid tumors) that stably express the gene for the enzyme luciferase are cultured with nonmalignant accessory cells (for example, stromal cells) for the selective quantification of tumor cell viability following drug treatment. The test is carried out in parallel on cultures of the tumor cells lacking the presence of stromal cells. CS-BLI is a high-throughput assay system that is able to identify stroma-induced chemo-resistance in various types of cancer.

The assay measures the amount of light emitted by living cancer cells. After treatment with a drug candidate, reduction in the amount of light being emitted indicates how proficient the drug was at killing tumor cells, and whether this effectiveness changes when normal cells are around the tumor. To determine whether the candidate compound is also toxic to normal cells, a "counter-screen,” is conducted to measure the effect of the compound on normal cells.

Results published in the March 14, 2010, online edition of the journal Nature Medicine revealed that in general drug candidates that acted powerfully against isolated samples of tumor cells were significantly less effective against the same types of tumor cells co-cultured with nonmalignant cells. However, in an exception to this trend, they found that the drug candidate reversine was more active against myeloma tumor cells when the cells were in contact with healthy cells of the bone marrow.

"Despite their often impressive results in the laboratory, for every 100 potential anticancer therapies administered in patients in clinical trials, only about eight prove safe and effective enough to receive Food and Drug Administration approval,” said senior author Dr. Constantine Mitsiades, professor of medical oncology at the Dana-Farber Cancer Institute. "This success rate is clearly not as high as we would like it to be, and one reason may be that so far we have not had a good way to account, at the earliest stages of laboratory testing, for the impact of the tumor microenvironment on these drugs.”

"The technique also provides a powerful tool for determining which biological mechanisms allow cancers to become resistant to certain treatments and which new therapies can neutralize those mechanisms,” said Dr. Mitsiades. "It will be of use in prioritizing candidate drugs for further rigorous study of their properties before embarking on clinical trials. This technique may show that the classical methods of studying candidate cancer drugs in laboratory conditions have overestimated the effectiveness of some agents, and underestimated others.

Related Links:
Dana-Farber Cancer Institute

New
Gold Member
Human Chorionic Gonadotropin Test
hCG Quantitative - R012
Verification Panels for Assay Development & QC
Seroconversion Panels
New
cTnI/CK-MB/Myo Test
Finecare cTnI/CK-MB/Myo Rapid Quantitative Test
New
Vaginitis Test
Allplex Vaginitis Screening Assay

Print article

Channels

Clinical Chemistry

view channel
Image: The tiny clay-based materials can be customized for a range of medical applications (Photo courtesy of Angira Roy and Sam O’Keefe)

‘Brilliantly Luminous’ Nanoscale Chemical Tool to Improve Disease Detection

Thousands of commercially available glowing molecules known as fluorophores are commonly used in medical imaging, disease detection, biomarker tagging, and chemical analysis. They are also integral in... Read more

Immunology

view channel
Image: The cancer stem cell test can accurately choose more effective treatments (Photo courtesy of University of Cincinnati)

Stem Cell Test Predicts Treatment Outcome for Patients with Platinum-Resistant Ovarian Cancer

Epithelial ovarian cancer frequently responds to chemotherapy initially, but eventually, the tumor develops resistance to the therapy, leading to regrowth. This resistance is partially due to the activation... Read more

Microbiology

view channel
Image: The lab-in-tube assay could improve TB diagnoses in rural or resource-limited areas (Photo courtesy of Kenny Lass/Tulane University)

Handheld Device Delivers Low-Cost TB Results in Less Than One Hour

Tuberculosis (TB) remains the deadliest infectious disease globally, affecting an estimated 10 million people annually. In 2021, about 4.2 million TB cases went undiagnosed or unreported, mainly due to... Read more

Pathology

view channel
Image: The ready-to-use DUB enzyme assay kits accelerate routine DUB activity assays without compromising data quality (Photo courtesy of Adobe Stock)

Sensitive and Specific DUB Enzyme Assay Kits Require Minimal Setup Without Substrate Preparation

Ubiquitination and deubiquitination are two important physiological processes in the ubiquitin-proteasome system, responsible for protein degradation in cells. Deubiquitinating (DUB) enzymes contain around... Read more

Technology

view channel
Image: The HIV-1 self-testing chip will be capable of selectively detecting HIV in whole blood samples (Photo courtesy of Shutterstock)

Disposable Microchip Technology Could Selectively Detect HIV in Whole Blood Samples

As of the end of 2023, approximately 40 million people globally were living with HIV, and around 630,000 individuals died from AIDS-related illnesses that same year. Despite a substantial decline in deaths... Read more

Industry

view channel
Image: The collaboration aims to leverage Oxford Nanopore\'s sequencing platform and Cepheid\'s GeneXpert system to advance the field of sequencing for infectious diseases (Photo courtesy of Cepheid)

Cepheid and Oxford Nanopore Technologies Partner on Advancing Automated Sequencing-Based Solutions

Cepheid (Sunnyvale, CA, USA), a leading molecular diagnostics company, and Oxford Nanopore Technologies (Oxford, UK), the company behind a new generation of sequencing-based molecular analysis technologies,... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.