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.
- 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 · 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 · 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 · 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.
- Pancreatic cancer (high CD73)
- NSCLC (especially KRAS/STK11-mutant)
- TNBC, ovarian, colorectal cancer
- Tregs, MDSCs and endothelium in the microenvironment
Latest papers
topQuery 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.
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