Targeted therapies for small cell lung cancer: Where do we stand?

Small cell lung cancer (SCLC) accounts for 15% of lung cancer cases and is associated with a dismal prognosis. Standard therapeutic regimens have been improved over the past decades, but without a major impact on patient survival. The development of targeted therapies based on a better understanding of the molecular basis of the disease is urgently needed. At the genetic level, SCLC appears very heterogenous, although somatic mutations targeting classical oncogenes and tumor suppressors have been reported. SCLC also possesses somatic mutations in many other cancer genes, including transcription factors, enzymes involved in chromatin modification, receptor tyrosine kinases and their downstream signaling components. Several avenues have been explored to develop targeted therapies for SCLC. So far, however, there has been limited success with these targeted approaches in clinical trials. Further progress in the optimization of targeted therapies for SCLC will require the development of more personalized approaches for the patients.

Incorporation of tissue-based genomic biomarkers into localized prostate cancer clinics.

Localized prostate cancer (PCa) is a clinically heterogeneous disease, which presents with variability in patient outcomes within the same risk stratification (low, intermediate or high) and even within the same Gleason scores. Genomic tools have been developed with the purpose of stratifying patients affected by this disease to help physicians personalize therapies and follow-up schemes. This review focuses on these tissue-based tools. At present, four genomic tools are commercially available: Decipher™, Oncotype DX®, Prolaris® and ProMark®. Decipher™ is a tool based on 22 genes and evaluates the risk of adverse outcomes (metastasis) after radical prostatectomy (RP). Oncotype DX® is based on 17 genes and focuses on the ability to predict outcomes (adverse pathology) in very low-low and low-intermediate PCa patients, while Prolaris® is built on a panel of 46 genes and is validated to evaluate outcomes for patients at low risk as well as patients who are affected by high risk PCa and post-RP. Finally, ProMark® is based on a multiplexed proteomics assay and predicts PCa aggressiveness in patients found with similar features to Oncotype DX®. These biomarkers can be helpful for post-biopsy decision-making in low risk patients and post-radical prostatectomy in selected risk groups. Further studies are needed to investigate the clinical benefit of these new technologies, the financial ramifications and how they should be utilized in clinics.