Research strategies of small molecules as chemotherapeutics to overcome multiple myeloma resistance

Eur J Med Chem. 2024 May 5:271:116435. doi: 10.1016/j.ejmech.2024.116435. Epub 2024 Apr 20.

Abstract

Multiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering from relapse, limited treatment options and uncontrolled disease progression after relapse. There are urgent needs to develop and explore novel MM treatment strategies to overcome drug resistance and improve efficacy. Here, we review the recent small molecule therapeutic strategies for MM, and introduce potential new targets and corresponding modulators in detail. In addition, this paper also summarizes the progress of multi-target inhibitor therapy and protein degradation technology in the treatment of MM.

Keywords: Drug resistance; Multiple myeloma; Potential targets; Small molecule; Structure-activity relationships.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Drug Resistance, Neoplasm* / drug effects
  • Humans
  • Molecular Structure
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / pathology
  • Proteasome Inhibitors / chemistry
  • Proteasome Inhibitors / pharmacology
  • Proteasome Inhibitors / therapeutic use
  • Small Molecule Libraries* / chemistry
  • Small Molecule Libraries* / pharmacology

Substances

  • Antineoplastic Agents
  • Small Molecule Libraries
  • Proteasome Inhibitors