Orchestrating smart therapeutics to achieve optimal treatment in small cell lung cancer: recent progress and future directions

Abstract

Small cell lung cancer (SCLC) is a recalcitrant malignancy with elusive mechanism of pathogenesis and dismal prognosis. Over the past decades, platinum-based chemotherapy has been the backbone treatment for SCLC. However, subsequent chemoresistance after initial effectiveness urges researchers to explore novel therapeutic targets of SCLC. Recent years have witnessed significant improvements in targeted therapy in SCLC. New molecular candidates such as Ataxia telangiectasia and RAD3-related protein (ATR), WEE1, checkpoint kinase 1 (CHK1) and poly-ADP-ribose polymerase (PARP) have shown promising therapeutic utility in SCLC. While immune checkpoint inhibitor (ICI) has emerged as an indispensable treatment modality for SCLC, approaches to boost efficacy and reduce toxicity as well as selection of reliable biomarkers for ICI in SCLC have remained elusive and warrants our further investigation. Given the increasing importance of precision medicine in SCLC, optimal subtyping of SCLC using multi-omics have gradually applied into clinical practice, which may identify more drug targets and better tailor treatment strategies to each individual patient. The present review summarizes recent progress and future directions in SCLC. In addition to the emerging new therapeutics, we also focus on the establishment of predictive model for early detection of SCLC. More importantly, we also propose a multi-dimensional model in the prognosis of SCLC to ultimately attain the goal of accurate treatment of SCLC.

Exploration of potential novel drug targets and biomarkers for small cell lung cancer by plasma proteome screening

“…Due to its rapid growth and lack of effective biomarkers, early diagnosis of SCLC is particularly challenging. In addition to the diagnostic challenges, treatment options for SCLC remain very limited, and there is a lack of effective drugs in clinical practice ( Zhang et al, 2023 ). While some progress has been made over the past few decades, the progress in SCLC treatment has been relatively slow compared to non-small cell lung cancer.…”

“…While the emergence of immunotherapy has provided a breakthrough in the treatment of SCLC, its clinical efficacy remains unsatisfactory, with most patients experiencing relapse in the short term ( Kang et al, 2023 ). The development of novel drugs for SCLC faces multiple challenges, including rapid growth and early metastasis, complex genetic characteristics, great tumor heterogeneity, and the issue of drug resistance, which make the search for effective drug targets and treatment strategies more difficult ( Megyesfalvi et al, 2023 ; Zhang et al, 2023 ).…”

Potential subtype-specific therapeutic approaches in small cell lung cancer

“…Figure 1 Notably, these distinct subtypes have not only been shown to correlate with different clinicopathological characteristics but bear prognostic significance and predictive relevance in terms of unique therapeutic vulnerabilities (Fig. 2[12 ▪▪ ]).…”