Version 1
: Received: 11 June 2024 / Approved: 12 June 2024 / Online: 12 June 2024 (11:58:20 CEST)
How to cite:
KAST, R. E. IC Regimen: Delaying Resistance to Lorlatinib in ALK Driven Cancers Using Repurposed Itraconazole and Cilostazol. Preprints2024, 2024060779. https://doi.org/10.20944/preprints202406.0779.v1
KAST, R. E. IC Regimen: Delaying Resistance to Lorlatinib in ALK Driven Cancers Using Repurposed Itraconazole and Cilostazol. Preprints 2024, 2024060779. https://doi.org/10.20944/preprints202406.0779.v1
KAST, R. E. IC Regimen: Delaying Resistance to Lorlatinib in ALK Driven Cancers Using Repurposed Itraconazole and Cilostazol. Preprints2024, 2024060779. https://doi.org/10.20944/preprints202406.0779.v1
APA Style
KAST, R. E. (2024). IC Regimen: Delaying Resistance to Lorlatinib in ALK Driven Cancers Using Repurposed Itraconazole and Cilostazol. Preprints. https://doi.org/10.20944/preprints202406.0779.v1
Chicago/Turabian Style
KAST, R. E. 2024 "IC Regimen: Delaying Resistance to Lorlatinib in ALK Driven Cancers Using Repurposed Itraconazole and Cilostazol" Preprints. https://doi.org/10.20944/preprints202406.0779.v1
Abstract
This paper presents data supporting the IC Regimen for potentiating the effectiveness of lorlatinib in treating ALK positive cancers, and specifically non-small cell lung cancer. Lorlatinib is an effective treatment for ALK driven non-small cell lung cancer and other ALK driven cancers. Lorlatinib inhibits ALK kinase and achieves good brain tissue levels, a common site for metastases in lung cancers. However, resistance to lorlatinib usually supervenes and the cancer awakens and starts growing again, resistant to lorlatinib. This paper analyses data indicating that adding two common generic drugs, itraconazole and cilostazol, to lorlatinib treatment may delay resistance development. Itraconazole is marketed worldwide as a generic antifungal drug that also inhibits Hedgehog signaling, CYP3A4, and the p-gp efflux pump. Cilostazol is a generic anti-thrombosis, phosphodiesterase 3 inhibiting drug that carries minimal bleeding risk. Cilostazol may enhance lorlatinib by deprivation of trophic growth factors supplied by platelets. Itraconazole may enhance lorlatinib effectiveness by reducing or stopping a Hedgehog centered amplifying feedback loop with ALK kinase. The combination of metastatic non-small cell lung cancer being a low-survival disease and the general safety itraconazole plus cilostazol augmentation, make a clinical trial of this trio worthwhile.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
