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Open research questions in Lung Cancer Research Studies

35 unresolved questions extracted from the limitations and future-work sections of 298 Lung Cancer Research Studies papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Chaperone-mediated autophagy (CMA) is involved in proteostasis, metabolic adaptation, and stress responses, but its cellular heterogeneity and prognostic relevance in SCLC remain unclear.

    CMA-associated cellular state remodeling defines prognostic heterogeneity and identifies ARRDC3 as a protective functional gene in small cell lung cancer · 2026 · DOI

  • Although numerous studies have examined HNSC and NSCLC independently, the common mol- ecules and pathways shared between these two malignancies remain poorly understood.

    Multi-omic discovery of SCG5 as a shared driver and prognostic biomarker in head-neck and non-small cell lung cancers · 2026 · DOI

  • In published studies evaluating anti-PD-1 therapy combined with anti-angiogenic agents without chemotherapy for advanced NSCLC, such as sintilimab plus anlotinib (13), CR rates have rarely been reported and are estimated to be below 5%.

    First-line penpulimab combined with anlotinib achieves complete response in an elderly patient with occult lung squamous cell carcinoma: a case report · 2026 · DOI

  • Existing biomarkers -- including PD-L1 expression and tumour mutational burden (TMB) -- are insufficiently discriminatory, and multimodal predictive models targeting primary resistance are still lacking to precisely drive patients treatment strategy.

    Multimodal profiling for prediction of primary resistance to anti-PD-(L)1 therapy in advanced non-small-cell lung cancer: the prospective PIONeeR biomarkers study · 2026 · DOI

  • The potential synergy between PEG–rhG-CSF and chemoimmunotherapy for efficacy enhancement remains to be validated in broader populations. Additionally, the generalizability of our efficacy findings is also limited to the specific population studied—patients with advanced squamous NSCLC—and should not be directly extrapolated to all NSCLC histological subtypes.

    Efficacy and safety of the combination of PEG–rhG-CSF with camrelizumab and chemotherapy in advanced squamous nonsmall cell lung cancer: A randomized controlled trial · 2026 · DOI

  • Therefore, IHC remains to be an impor Initial subtyping approaches have explored the use of immunohistochemistry (IHC) for these factors 9,10,40, although this approach is limited by the tissue requirements, challenges in quantitation, heterogeneity in staining, and the observation that no single marker specifically can unequivocally define each subgroup 9,40.

    Tumor- and circulating-free DNA methylation identifies clinically relevant small cell lung cancer subtypes · 2024 · DOI

  • A recent study found that 35-40% of human SCLCs express both ASCL1 and NEUROD1, but the mechanisms driving ASCL1 and NEUROD1 intra-tumoral heterogeneity are not well understood.

    Abstract 5774: Small cell lung cancer subtype plasticity is regulated by KDM6A · 2023 · DOI

  • The role of immunotherapy for LCNEC is uncertain and predictive biomarkers for LCNEC immunotherapy response are not well characterized.

    Abstract B026: RB1 loss is associated with greater PD-1:PD-L1 interaction in Pulmonary Large Cell Neuroendocrine Carcinoma · 2026 · DOI

  • The inability of single-patient-derived PDOs to fully capture the complex biological heterogeneity of PSC represents a key limitation of this study.

    Establishment, functional dissection, and single-cell transcriptomal characteristics of patient-derived pulmonary sarcomatoid carcinoma organoids · 2026 · DOI

  • This supports further investigation of SSTR2-targeted RPT in combination with ICI in patients with ES-SCLC.

    LuSato-1: Phase I study of <sup>177</sup> Lu-SSO110 with <sup>68</sup> Ga-SSO120 companion imaging in patients with extensive stage small cell lung cancer (ES-SCLC) on maintenance treatment with immune checkpoint inhibition (ICI). · 2026 · DOI

  • Veterans are particularly underrepresented in clinical trials due to comorbidities and performance status, leaving the real-world effectiveness of chemo-immunotherapy and immune biomarkers in this population poorly defined.

    Evaluation of survival after chemo-immunotherapy in veterans with extensive-stage small cell lung cancer and brain metastases. · 2026 · DOI

  • However, the impact of these changes on the immune microenvironment and vice versa is not understood, limiting the identification of novel immunotherapy approaches in this setting.

    Multiomic spatial analysis of tumor microenvironment during neuroendocrine (NE) transformation in <i>EGFR</i> -mutant LUAD. · 2026 · DOI

  • and actionable targets. Wang et al. deliver a seminal resource for the SCLC community, unraveling its cellular heterogeneity…

    Unraveling the intricacies of small cell lung cancer: FAK splicing variants as a new feature and therapeutic vulnerability of small cell lung cancer · 2026 · DOI

  • Neoadjuvant Ipi+Nivo+CT enhances pathologic responses and warrants further study in operable NSCLC.

    Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial · 2023 · DOI

  • It is necessary to know correct treatment of these patients but there is a lack of evidence-based data regarding this age group, leading to an undertreatment based on a supposed lack of tolerance to radical treatments.

    Treatment of lung cancer in the elderly: Influence of comorbidity on toxicity and survival · 2011 · DOI

Most-cited papers in Lung Cancer Research Studies

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35 open questions have been extracted from the limitations and future-work passages of 298 Lung Cancer Research Studies papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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