Modulating the Epigenetic Machinery for Increased SSTR2 Expression in Small-Cell Lung Cancer Cells

Aim/Introduction: Peptide receptor radionuclide therapy for neuroendocrine tumor (NET) patients is effective, however, complete responses are rare. To improve treatment outcome, we aim to enhance somatostatin type-2 receptor (SSTR2) expression using histone deacetylase inhibitors (HDACis). Our previous studies using the HDACi valproic acid showed promising results in vitro, however, in vivo studies did not demonstrate increased SSTR2-mediated [¹⁷⁷Lu]Lu-DOTATATE uptake. Therefore we investigated the potential of other HDACis, targeting different HDAC enzyme classes and/or having longer half-lives in vivo, in high SSTR2-expressing small-cell lung cancer (SCLC) cells. In addition, we compared the results to that obtained in low SSTR2-expressing NET cells.