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Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer

Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany
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Cancers 2019, 11(5), 690; https://doi.org/10.3390/cancers11050690
Received: 29 March 2019 / Revised: 29 April 2019 / Accepted: 14 May 2019 / Published: 17 May 2019
(This article belongs to the Special Issue Targeted Therapy for Small Cell Lung Cancer)
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Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkpoint inhibition yielded improved overall survival. Although there are promising molecular pathways with potential therapeutic impacts, targeted therapies are still not an integral part of routine treatment. Against this background, we evaluated current literature for potential new molecular candidates such as surface markers (e.g., DLL3, TROP-2 or CD56), apoptotic factors (e.g., BCL-2, BET), genetic alterations (e.g., CREBBP, NOTCH or PTEN) or vascular markers (e.g., VEGF, FGFR1 or CD13). Apart from these factors, the application of so-called ‘poly-(ADP)-ribose polymerases’ (PARP) inhibitors can influence tumor repair mechanisms and thus offer new perspectives for future treatment. Another promising therapeutic concept is the inhibition of ‘enhancer of zeste homolog 2’ (EZH2) in the loss of function of tumor suppressors or amplification of (proto-) oncogenes. Considering the poor prognosis of SCLC patients, new molecular pathways require further investigation to augment our therapeutic armamentarium in the future. View Full-Text
Keywords: SCLC; anti-angiogenesis; apoptosis; epigenetics; targeted therapy SCLC; anti-angiogenesis; apoptosis; epigenetics; targeted therapy
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Schulze, A.B.; Evers, G.; Kerkhoff, A.; Mohr, M.; Schliemann, C.; Berdel, W.E.; Schmidt, L.H. Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer. Cancers 2019, 11, 690.

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