The efficacy of selinexor (KPT-330), an XPO1 inhibitor, on non-hematologic cancers: a comprehensive review

J Cancer Res Clin Oncol. 2023 May;149(5):2139-2155. doi: 10.1007/s00432-022-04247-z. Epub 2022 Aug 8.

Abstract

Purpose: Selinexor is a novel XPO1 inhibitor which inhibits the export of tumor suppressor proteins and oncoprotein mRNAs, leading to cell-cycle arrest and apoptosis in cancer cells. While selinexor is currently FDA approved to treat multiple myeloma, compelling preclinical and early clinical studies reveal selinexor's efficacy in treating hematologic and non-hematologic malignancies, including sarcoma, gastric, bladder, prostate, breast, ovarian, skin, lung, and brain cancers. Current reviews of selinexor primarily highlight its use in hematologic malignancies; however, this review seeks to summarize the recent evidence of selinexor treatment in solid tumors.

Methods: Pertinent literature searches in PubMed and the Karyopharm Therapeutics website for selinexor and non-hematologic malignancies preclinical and clinical trials.

Results: This review provides evidence that selinexor is a promising agent used alone or in combination with other anticancer medications in non-hematologic malignancies.

Conclusion: Further clinical investigation of selinexor treatment for solid malignancies is warranted.

Keywords: KPT-330; Non-hematologic cancer; SINE compounds; Selinexor; Solid malignancy.

Publication types

  • Review

MeSH terms

  • Active Transport, Cell Nucleus
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Humans
  • Hydrazines / pharmacology
  • Hydrazines / therapeutic use
  • Karyopherins / metabolism
  • Male
  • Multiple Myeloma* / drug therapy
  • Triazoles / pharmacology
  • Triazoles / therapeutic use

Substances

  • selinexor
  • Karyopherins
  • Antineoplastic Agents
  • Triazoles
  • Hydrazines