In Search of the Long-Desired ‘Copernican Therapeutic Revolution’ in Small-Cell Lung Cancer
AbstractSmall-cell lung cancer has defied our scientific community for decades. Chemotherapy has been the mainstay treatment for small-cell lung cancer (SCLC) and unlike its counterpart, non-small cell lung cancer, no significant therapeutic breakthroughs have been made since the 1970s. Among the reasons for this slow-paced therapeutic development, one that stands out is the distinctive and almost universal loss of function of the tumour suppressor genesTP53 andRB1 in this disease, for which pharmacological activation has yet to be achieved, despite having been highly sought after. Although no molecularly targeted approach has been approved for clinical practice thus far, several strategies are currently exploring the potential to drug the tumour ’s “Achilles heel” that stems from essential pathways regulating DNA-damage response. Most recently, we have witnessed newfound reasons to hope, as the combination of immunotherapy and systemic chemotherapy has improved survival outcomes, representing the first landmark achievement in decades and a new standard of care for patients with extensive disease SCLC. However, continuous efforts are still needed towards a better understanding of the molecular pathways that singularise this tumour to eventually identify the predictive biomarkers that might result in the development of a more rati onal therapeutic approach, including the use of immunotherapy combinations. In this review we aim to uncover critical aspects of the immune mi...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research
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