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Review
. 2021 May 10;10(5):1148.
doi: 10.3390/cells10051148.

OPALS: A New Osimertinib Adjunctive Treatment of Lung Adenocarcinoma or Glioblastoma Using Five Repurposed Drugs

Richard E Kast  1 , Marc-Eric Halatsch  2 , Rafael Rosell  3
Affiliations
Review

OPALS: A New Osimertinib Adjunctive Treatment of Lung Adenocarcinoma or Glioblastoma Using Five Repurposed Drugs

Richard E Kast et al. Cells. .

Abstract

Background: Pharmacological targeting aberrant activation of epidermal growth factor receptor tyrosine kinase signaling is an established approach to treating lung adenocarcinoma. Osimertinib is a tyrosine kinase approved and effective in treating lung adenocarcinomas that have one of several common activating mutations in epidermal growth factor receptor. The emergence of resistance to osimertinib after a year or two is the rule. We developed a five-drug adjuvant regimen designed to increase osimertinib's growth inhibition and thereby delay the development of resistance. Areas of Uncertainty: Although the assembled preclinical data is strong, preclinical data and the following clinical trial results can be discrepant. The safety of OPALS drugs when used individually is excellent. We have no data from humans on their tolerability when used as an ensemble. That there is no data from the individual drugs to suspect problematic interaction does not exclude the possibility.

Data sources: All relevant PubMed.org articles on the OPALS drugs and corresponding pathophysiology of lung adenocarcinoma and glioblastoma were reviewed. Therapeutic Opinion: The five drugs of OPALS are in wide use in general medicine for non-oncology indications. OPALS uses the anti-protozoal drug pyrimethamine, the antihistamine cyproheptadine, the antibiotic azithromycin, the antihistamine loratadine, and the potassium sparing diuretic spironolactone. We show how these inexpensive and generically available drugs intersect with and inhibit lung adenocarcinoma growth drive. We also review data showing that both OPALS adjuvant drugs and osimertinib have data showing they may be active in suppressing glioblastoma growth.

Keywords: EGFR; NSCLC; cancer stem cells; glioblastoma; osimertinib; repurposing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic showing escape from osimertinib growth inhibition by increasing expression of non-mutated EGFR. References in text.
See this image and copyright information in PMC

References

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