Data from <i>In Vivo</i> Validation of PAPSS1 (3′-phosphoadenosine 5′-phosphosulfate synthase 1) as a Cisplatin-sensitizing Therapeutic Target

• DOI: 10.1158/1078-0432.c.6526980.v1
• Publication Date: 2023-04-01T06:27:08Z
• Authors: Ada W.Y. Leung; Chansey J. Veinotte; Nicole Melong; Min Hee Oh; Kent Chen; Katey S.S. Enfield; Ian Backstrom; Corinna Warburton; Donald Yapp; Jason N. Berman; Marcel B. Bally; William W. Lockwood

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Our previous screening efforts found that inhibition of PAPSS1 increases the potency DNA-damaging agents in non–small cell lung cancer (NSCLC) lines. Here, we explored clinical relevance and further investigated it as a therapeutic target preclinical model systems.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; expression cisplatin IC&lt;sub&gt;50&lt;/sub&gt; values were assessed 52 adenocarcinoma Effects on A549 sensitivity under hypoxic starvation conditions, 3D spheroids, well zebrafish mouse xenografts, evaluated. Finally, association between levels survival patients treated with standard chemotherapy was assessed.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; results show positive correlation low increased adenocarcinoma. &lt;i&gt;In vitro&lt;/i&gt;, potentiation effect greatest when cells serum-starved conditions. When low-dose cisplatin, PAPSS1-deficient spheroids showed 58% reduction size compared control cells. vivo&lt;/i&gt;, suppression treatment inhibited proliferation tumor xenografts significantly delayed development subcutaneous tumors mice. Clinical data suggest NSCLC ovarian survive longer following platinum-based chemotherapy.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; These enhances activity multiple systems may serve biomarker for platin patients. Developing strategies to conjunction offer an approach improving outcomes. &lt;i&gt;Clin Cancer Res; 23(21); 6555–66. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;