Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Small cell lung cancer (SCLC) accounts for about 15% of lung cancer. Although SCLC often responds favorably to combined-modality chemotherapy at the initial treatment, resistant tumors develop rapidly, which makes SCLC one of the representative cancers refractory to any therapeutic approaches. Moreover, molecular targeting therapy has not been developed for SCLC so far. Therefore, novel approaches to the diagnosis and treatment of SCLC on the basis of molecular understanding would be prerequisite to control this refractory cancer. One of the most critical issues of SCLC is its early detection in the initial screening and after chemotherapy. For this purpose, pro-gastrin releasing peptide (ProGRP) and neuron specific enolase (NSE) are widely used for serum markers for detection of SCLC, although combination of ProGRP and NSE can detect at most 60% of SCLC. We have previously demonstrated that CADM1, a member of the immunoglobulin superfamily cell adhesion molecules, is highly expressed in around 75% of SCLC. In addition, SCLC expresses a splicing variant, CADM1v8/9, which is observed specifically in normal testis. Here, we report that the extracellular fragment of CADM1v8/9 is digested by ADM17 and released into cell medium or human serum. So, we generated specific monoclonal antibody against CADM1v8/9 using Cadm1-deficient mice and developed a serum diagnostic marker system for SCLC. Preliminary study shows that CADM1v8/9 detects 47% of SCLC with specificity of 92%, which is independent of and partly overlapped with the cases detected by ProGRP or NSE. CADM1v8/9 can detect 25% of patients with limited disease and 77% of patients with extensive disease of SCLC. Furthermore, the amount of CADM1v8/9 fragments well correlates with the disease activity of SCLC before and after chemotherapy. These findings indicate that detection of CADM1v8/9 in serum from patients is a novel and promising approach to detect and follow up SCLC patients. Since CADM1 is highly expressed in cell membrane of SCLC, CADM1 would also provide a promising target for the treatment of SCLC.</jats:p>
<jats:p>Citation Format: Takeshi Ito, Toko Funaki, Goh Tanaka, Takahide Nagase, Yoshinori Murakami. CADM1 is a novel serum marker for small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1129.</jats:p>