Carbonic Anhydrase IX in Renal Cell Carcinoma, Implications for Disease Management

Int J Mol Sci. 2020 Sep 28;21(19):7146. doi: 10.3390/ijms21197146.

Abstract

Carbonic Anhydrase IX (CAIX) is a well-described enzyme in renal cell carcinoma, with its expression being regulated by the hypoxia-inducible factor 1 alpha, it is known for interfering with hypoxia processes. Renal carcinoma encompasses a broad spectrum of histological entities and is also described as a heterogeneous malignant tumor. Recently, various combinations of checkpoint inhibitors and targeted therapies have been validated to manage this disease. Reliable markers to confirm the diagnosis, estimate the prognosis, predict or monitor the treatment response are required. Molecular imaging developments allow a comprehensive analysis of the tumor, overcoming the spatial heterogeneity issue. CAIX, being highly expressed at the tumor cell surfaces of clear cell renal carcinoma, also represents a potential treatment target. In this manuscript we reviewed the current knowledge from the literature on the pathophysiological interactions between renal cell carcinoma and CAIX, the role of CAIX as a marker for diagnosis, prognosis, treatment monitoring and molecular imaging, and the potential target for therapeutic strategies.

Keywords: carbonic anhydrase IX; clear cell; immunohistochemistry; molecular imaging; renal cell carcinoma; targeted therapy.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents, Immunological / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carbonic Anhydrase IX / antagonists & inhibitors
  • Carbonic Anhydrase IX / genetics*
  • Carbonic Anhydrase IX / metabolism
  • Carcinoma, Renal Cell / diagnostic imaging
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / immunology
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / genetics
  • Disease Management
  • Gene Expression Regulation, Neoplastic*
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Hypoxia / diagnostic imaging
  • Hypoxia / drug therapy
  • Hypoxia / genetics*
  • Hypoxia / immunology
  • Kidney Neoplasms / diagnostic imaging
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / immunology
  • Molecular Imaging / methods
  • Molecular Targeted Therapy / methods*
  • Prognosis
  • Recombinant Fusion Proteins / therapeutic use
  • Signal Transduction

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • G250 monoclonal antibody
  • Recombinant Fusion Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • CA9 protein, human
  • Carbonic Anhydrase IX