Small Cell Lung Cancer from Traditional to Innovative Therapeutics: Building a Comprehensive Network to Optimize Clinical and Translational Research

Abstract

Small cell lung cancer (SCLC) is an aggressive, complex disease with a distinct biology that contributes to its poor prognosis. Management of SCLC is still widely limited to chemotherapy and radiation therapy, and research recruitment still poses a considerable challenge. Here, we review the current standard of care for SCLC and advances made in utilizing immunotherapy. We also highlight research in the development of targeted therapies and emphasize the importance of a team-based approach to make clinical advances. Building an integrative network between an academic site and community practice sites optimizes biomarker and drug target discovery for managing and treating a difficult disease like SCLC.

Topological signatures in regulatory network enable phenotypic heterogeneity in small cell lung cancer

“…Our results highlight an important step in decoding the design principles of underlying regulatory network for phenotypic plasticity and heterogeneity in aggressive cancers such as SCLC. SCLC has no targeted therapy available till date (Subbiah et al, 2020), a limitation that is expected to be overcome by recent surge in high-throughput experimental data collection for SCLC and computational approaches to identify SCLC subtypes for clinical action Stewart et al, 2020;Tlemsani et al, 2020;Udyavar et al, 2017;Wooten et al, 2019). An abysmal, if any, correlation between mutational profiles and distinct SCLC subtypes (George et al, 2015), and multistability in SCLC network, argue for non-genetic causes of phenotypic heterogeneity.…”

Topological signatures in regulatory network enable phenotypic heterogeneity in small cell lung cancer

“…Our results highlight an important step in decoding the design principles of underlying regulatory network for phenotypic plasticity and heterogeneity in aggressive cancers such as SCLC. SCLC has no targeted therapy available till date (Subbiah et al, 2020), a limitation that is expected to be overcome by recent surge in high-throughput experimental data collection for SCLC and computational approaches to identify SCLC subtypes for clinical action (Salgia et al, 2018; Stewart et al, 2020; Tlemsani et al, 2020; Udyavar et al, 2017; Wooten et al, 2019). An abysmal, if any, correlation between mutational profiles and distinct SCLC subtypes (George et al, 2015), and multistability in SCLC network, argue for non-genetic causes of phenotypic heterogeneity.…”

Systematic Review and Network Meta-Analysis of Immune Checkpoint Inhibitors in Combination with Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Carcinoma

“…The most common risk factor for SCLC is smoking tobacco, and up to 98% of patients with SCLC have a history of smoking. SCLC is characterized by multiple genetic alterations, reflecting its genomic instability [1,2]. The majority of SCLCs express alterations in chromosome 3p and mutations in RB1, TP53, RASSF1, MYC, FGFR1, and PTEN [3,4].…”

“…There is no standard of care beyond second-line therapy. Systemic therapy for SCLC patients has not changed substantially in several decades [2,6]. Consequently, there is an urgent medical need to bring new treatment options to SCLC patients.…”

“…SCLC is a tumor with one of the highest rates of somatic mutations and this characteristic can result in a higher likelihood of identifying tumor-specific neoantigens that may ultimately trigger an adaptive immune response that is capable of detecting and eradicating tumor cells [1,2]. Preclinical data has demonstrated that treatment with antibodies specific for anti-cytotoxic T lymphocyte associated antigen 4 (CTLA-4) can restore an immune response through the increased accumulation and survival of memory T cells and depletion of regulatory T cells (Tregs).…”