Recent developments in small molecule therapies for renal cell carcinoma

Eur J Med Chem. 2017 Dec 15:142:383-392. doi: 10.1016/j.ejmech.2017.08.007. Epub 2017 Aug 9.

Abstract

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and is known to be the 10th most common type of cancer in the world. Most of the currently available RCC drugs are tyrosine kinase inhibitors (TKIs). However, combination therapies of TKIs and immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors are the focus of most of the final stage clinical trials. Meanwhile, other small molecule therapies for RCC that target indoleamine-2,3-dioxygenase (IDO1), glutaminase, C-X-C chemokine receptor 4 (CXCR4), and transglutaminase 2 (TG2) are emerging as the next generation of therapeutics. In this review, these three major streams for the development of small molecule drugs for RCC are described.

Keywords: Anti-VEGF inhibitors; CXCR4 antagonist; Glutaminase inhibitor; IDO1 inhibitor; Immune checkpoint inhibitors; Renal cell carcinoma; Transglutaminase 2 inhibitor; Tyrosine kinase inhibitors; mTOR inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Drug Discovery
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Molecular Targeted Therapy
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Small Molecule Libraries / therapeutic use*

Substances

  • Antineoplastic Agents
  • Small Molecule Libraries