<p>Orphan Drugs in Development for the Treatment of Small-Cell Lung Cancer: Emerging Data on Lurbinectedin</p>

Abstract

Lung cancer is the leading cause of death of all cancer entities and small-cell lung cancer (SCLC) is the most malignant subtype. Despite good initial response to chemotherapy, many patients relapse early and success of second line treatment remains poor. For years, no relevant improvement of second line treatment has been achieved in the field of SCLC. Lurbinectedin, a novel RNA-polymerase II inhibitor has shown promising results in pretreated SCLC patients as single agent and in combination with other chemotherapeutic drugs leading to an orphan drug designation from the FDA. This article reviews the current data on this emerging substance and its impact on the treatment of SCLC.

Marine Natural Products in Clinical Use

“…Inspired by the discovery of these successfully marketed drugs and their diversity in structure and function, we could also use their valuable and specific structural backbones to further optimize and design a series of better marine drugs. By maintaining the skeletal structure of trabectedin and replacing the tetrahydroisoquinoline ring with tetrahydro β-carboline, the derivative lurbinectedin shares a similar mechanism of action with trabectedin and selectively inhibits RNA polymerase II transcription in SCLC [ 226 ]. In conclusion, these factors will help inspire researchers to explore all possible combinations of factors for novel drug design rather than to limit themselves to traditional drug characteristics.…”

Antibody-Drug Conjugate Targeting c-Kit for the Treatment of Small Cell Lung Cancer

“…In addition, lurbinectedin covalently binds to the minor groove of the DNA duplex, resulting in double-strand DNA breaks. Furthermore, lurbinectedin inhibits RNA-polymerase II activity and promotes its ubiquitin-mediated proteasomal degradation [47]. Thus, we hypothesized that combination therapy with carboplatin/etoposide or lurbinectedin may increase therapeutic efficacy.…”

Development of Marine-Derived Compounds for Cancer Therapy

“…In the meantime, lurbinectedin (Zepzelca), a derivative of ecteinascidin (a marine agent isolated from the sea squirt species Ecteinascidia turbinate), was approved by the FDA to treat metastatic small-cell lung cancer (SCLC) in June 2020 [8]. Structurally similar to trabectedin, lurbinectedin can also covalently bind to the DNA promoter and lead to the break of DNA double strands, causing apoptosis of cancer cells [27,28]. Moreover, it can also inhibit the activity of RNA polymerase II and promote its degradation, which also leads to the DNA double-strand break of cancer cells [29].…”