Quantitative high-throughput drug screening can identify
novel agents in different therapeutic categories and drugs with nonclassic
chemotherapy mode of action, according to study results published online in
The Journal of Clinical Endocrinology & Metabolism.
To identify agents with an anticancer effect in
thyroid cancer cell lines, researchers used quantitative
high-throughput drug screening to examine the accumulated NIH Chemical Genomics
Center’s Pharmaceutical Collection. The quantitative high-throughput drug
screening, which contained 2,816 approved drugs and bioactive compounds, used
concentration response curve information to identify 244 active compounds in
the human papillary thyroid cancer cell line TPC-1, 40 of which had
high-confidence activity.
Of the 40 compounds with high-confidence activity —
distributed across various therapeutic categories and with different modes of
drug action — 16 had efficacy of more than 60% and a 50% inhibitory
concentration (IC50) of less than 1.7 mcM. Enrichment analysis of
active agents in each drug category indicated that although a small quantity
(12%) of antineoplastic drugs showed activity in the thyroid cancer cells, more
than 25% of anti-obesity and cardiotonic drugs demonstrated potent activity.
To test whether these drugs had specific anticancer
activity, the researchers said they compared the antiproliferative activity of
the same drug library in several normal and cancer cell lines and primary
culture of
chronic lymphocytic leukemia cells from patients. Further
analysis demonstrated that many compounds with activity against TPC-1 cells
showed no cytotoxicity when tested in normal cells; conversely, many drugs that
showed antiproliferative effect in other tested cancer cell types did not
express activity in TPC-1 cells.
“The compounds found to have potent activity in our
screen represent possible opportunities to repurpose these drugs for the
treatment of patients with aggressive recurrent or metastatic thyroid
cancer,” Electron Kebebew, MD, of the NCI in Bethesda, Md., and one
of the study researchers, said in a press release. “Clinicians can more
readily translate these findings into therapy when the drug characteristics are
well known. The drugs can then be used in developing clinical trials or, in
some cases, for off-label use.”
Disclosure: The researchers report no relevant
financial disclosures.
Investigators at NCI and NHGRI collaborated to mine the NIH Pharmaceutical Collection of 2800 approved and investigational drugs via a high throughput screen toward discovering agents with anti-tumor activity in thyroid cancer. In addition to antineoplastic agents, they found a wide range of drugs that displayed anti-proliferative activity on thyroid cancer cell lines, including cardiovascular and anti-obesity agents. Their strategy, often called repurposing or repositioning, is based on discovering novel uses for agents already shown to be safe in humans. By avoiding pitfalls of conventional drug development, repurposing offers higher success rates and lower costs. Nonetheless, dose, formulation, FDA and legal concerns can all slow the adaptation of old drugs to new uses.
Ralph Weichselbaum, MD
HemOnc Today Editorial Board member
Stephen Kron, MD, PhD
Professor,
Department of Molecular Genetics
and Cell Biology
The University of Chicago
Disclosure: Dr. Weichselbaum and Dr. Kron are co-founders of a drug re-purposing company, Oncosenescence.