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Published on: December 1, 2016
Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer
Arik Bernard Schulze1, Georg Evers2, Andrea Kerkhoff3
1Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany. arikbernard.schulze@ukmuenster.de.
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.
Insights
Small cell lung cancer (SCLC) remains aggressive despite chemotherapy. This review explores novel molecular targets, including surface markers, apoptotic factors, and genetic alterations, to improve SCLC treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Small cell lung cancer (SCLC) is an aggressive subtype of lung cancer with frequent relapses after initial chemotherapy.
- Current standard treatment involves platinum-based chemotherapy with etoposide, enhanced by atezolizumab for extensive-stage disease, improving survival.
- Despite advances, targeted therapies are not yet standard, highlighting the need for new treatment strategies.
Purpose of the Study:
- To review current literature for novel molecular candidates for SCLC treatment.
- To identify potential therapeutic targets including surface markers, apoptotic factors, genetic alterations, and vascular markers.
- To explore emerging concepts like PARP inhibitors and EZH2 inhibition for SCLC.
Main Methods:
- Literature review of current research on SCLC molecular pathways.
- Evaluation of potential therapeutic targets such as DLL3, TROP-2, CD56, BCL-2, BET, CREBBP, NOTCH, PTEN, VEGF, FGFR1, and CD13.
- Assessment of novel therapeutic strategies including poly-(ADP)-ribose polymerases (PARP) inhibitors and enhancer of zeste homolog 2 (EZH2) inhibition.
Main Results:
- Identified several potential molecular targets for SCLC, including surface markers (DLL3, TROP-2, CD56), apoptotic factors (BCL-2, BET), genetic alterations (CREBBP, NOTCH, PTEN), and vascular markers (VEGF, FGFR1, CD13).
- Highlighted the potential of PARP inhibitors to affect tumor repair mechanisms.
- Recognized EZH2 inhibition as a promising strategy for targeting tumor suppressor loss or oncogene amplification.
Conclusions:
- Novel molecular pathways and targeted therapies show promise for augmenting the treatment of SCLC.
- Further investigation into these molecular candidates is crucial to expand therapeutic options for SCLC patients with poor prognoses.
- Exploring agents like PARP inhibitors and EZH2 inhibitors could offer new avenues for SCLC treatment.
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