OnCo
targetsTarget

CD73 / adenosine axis

CD73 is an enzyme on tumour and immune cells that converts ATP breakdown products into adenosine, a powerful immune-suppressant; blocking it or the adenosine receptors was a major immunotherapy hope that has not yet delivered.

CD39 converts extracellular ATP to AMP and CD73 (NT5E) converts AMP to adenosine, which suppresses T and NK cells via A2A/A2B receptors; hypoxia drives the axis. Oleclumab (anti-CD73) plus durvalumab improved PFS in the phase 2 COAST trial (stage III NSCLC) but the phase 3 PACIFIC-9 result is pending; quemliclustat (CD73 inhibitor) is in phase 3 in pancreatic cancer (PRISM-1); A2A antagonists (ciforadenant, etrumadenant, taminadenant) gave modest single-agent signals in RCC and prostate cancer and several were discontinued. CD39 antibodies (TTX-030) and uliledlimab continue in trials.

CD73 / adenosine axis: what it is and how drugs act on it · animated generic schematic, not to scale
  • Target · the protein and the cell it sits on
  • Drug · antibody, small molecule, cell or radioligand
  • Effect · signal, damage or kill

In plain words · CD73 is an enzyme on tumour and immune cells that converts ATP breakdown products into adenosine, a powerful immune-suppressant; blocking it or the adenosine receptors was a major immunotherapy hope that has not yet delivered.

  1. 1 · What it is

    CD73 is an enzyme on tumour and immune cells that converts ATP breakdown products into adenosine, a powerful immune-suppressant; blocking it or the adenosine receptors was a major immunotherapy hope that has not yet delivered.

  2. 2 · What goes wrong in cancer

    Ecto-5'-nucleotidase anchored by GPI; produces adenosine that binds Gs-coupled A2A/A2B receptors, raising cAMP/PKA in lymphocytes and blunting TCR signalling, cytokine release and cytotoxicity; also promotes Treg and MDSC function.

  3. 3 · How drugs use it

    No product in this corpus aims at CD73 / adenosine axis yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.

Biology

Ecto-5'-nucleotidase anchored by GPI; produces adenosine that binds Gs-coupled A2A/A2B receptors, raising cAMP/PKA in lymphocytes and blunting TCR signalling, cytokine release and cytotoxicity; also promotes Treg and MDSC function.

Where it is found
  • Pancreatic cancer (high CD73)
  • NSCLC (especially KRAS/STK11-mutant)
  • TNBC, ovarian, colorectal cancer
  • Tregs, MDSCs and endothelium in the microenvironment
Class
enzyme · NT5E

Latest papers

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Query for this target: (TITLE:"CD73 / adenosine axis" OR ABSTRACT:"CD73 / adenosine axis" OR TITLE:"NT5E" OR ABSTRACT:"NT5E") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CD73 / adenosine axis, not a curated reading list.

Connected

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