Exploring the Efficacy of LP184 in NSCLC with Gene Mutations

Lantern Pharma (a pharmaceutical company developing targeted cancer therapies) created a new drug candidate and next generation member of the acylfulvene class of prodrugs, named LP-184. Researchers from Lantern Pharma and REPROCELL (a commercial contract research organization) conducted a study to test the anti-tumor activity of this preclinical compound in a variety of NSCLC cell lines. In 2021, Oncotarget published the research paper the team authored, entitled, “The acylfulvene alkylating agent, LP-184, retains nanomolar potency in non-small cell lung cancer carrying otherwise therapy-refractory mutations.” Despite its highly-synthetic sounding name, LP-184’s lead product (Illudins) is derived from, you guessed it, Jack-o-Lantern mushrooms. “Acylfulvenes have been derived from cytotoxic agents called Illudins, isolated from Jack-o-Lantern mushroom (Omphalotus illudens), that retain and improve the cytotoxicity of parent Illudins for use as anticancer agents.” The anti-tumor activity of this compound is based on activation through reductive mechanisms when metabolized, mediated by enzymes such as Prostaglandin Reductase 1 (PTGR1). PTGR1 is known to be upregulated in some tumors, including tumors with mutations in the gene KEAP1. Researchers investigated LP-184 sensitivity in NSCLC cell lines with individual or combined gene mutations in KEAP1, KRAS, TP53, and STK11. “There is a high unmet need for effective therapies for NSCLC harboring mutations in these genes that have not only been considered undruggable till date but also are associated with loss of efficacy or resistance to multiple therapeutic strategies, at least in frontline regimens.” LP-184 was tested in vitro in 19 primary and metastatic NSCLC cell lines to determine the range of NSCLC settings that this compound might work best in. Clinical data analyses were also conducted by the researchers to predict tumor responsiveness to LP-184. In addition, the compound was examined in two mouse models of primary lung cancer. Mouse models were tested for sensitivity to LP-184 in both two- and three-dimensional culture systems. “We sought to assess LP-184 activity in a panel of selected NSCLC adenocarcinoma cell lines, determine associations between genomic and transcriptomic profiles and responses of cell lines tested, and compare in vitro potency of LP-184 with that of approved chemotherapy agents.” Full blog - https://www.impactjournals.com/journals/blog/oncotarget/trending-with-impact-promising-non-small-cell-lung-cancer-prodrug/ Press release - https://www.oncotarget.com/news/pr/retaining-nanomolar-potency-in-lung-cancer-with-therapy-refractory-mutations/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632/oncotarget.27943 DOI - https://doi.org/10.18632/oncotarget.27943 Full text - https://www.oncotarget.com/article/27943/text/ Correspondence to - Aditya Kulkarni - aditya@lanternpharma.com Keywords - non-small cell lung cancer, acylfulvene, alkylating agent, PTGR1, LP-184 About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105