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Open research questions in Lung Cancer Treatments and Mutations

54 unresolved questions extracted from the limitations and future-work sections of 407 Lung Cancer Treatments and Mutations papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Abstract Background Cytoskeleton-associated protein 2 (CKAP2) plays a role in tumor proliferation, but its causal relationship with lung cancer remains unclear.

    Genetic evidence for a potential role of cytoskeleton-associated protein 2 in lung squamous cell carcinoma: a bidirectional mendelian randomization study · 2026 · DOI

  • Fibroblast growth factor receptor 1 (FGFR1) copy number (CN) gain is a prevalent genomic aberration in LUSC; nevertheless, the correlation between FGFR1 CN gain and ICI therapeutic efficacy has not yet been clarified.

    FGFR1 copy number gain is independently associated with shorter progression-free survival in advanced lung squamous cell carcinoma treated with first-line immune checkpoint inhibitor-based therapy · 2026 · DOI

  • Lung adenocarcinoma a progress from preinvasive lesions to invasive cancer; however, early evolutionary events in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) remain poorly defined, particularly in East Asian populations enriched for EGFR mutations.

    Distinct Evolutionary Trajectories in Early Lung Adenocarcinoma: Age Related Pathway with Epidermal Growth Factor Receptor with Genome Doubling and Smoking-Driven Pathway · 2026 · DOI

  • This case provides a clinical clue for the treatment of osimertinib-resistant L858R/C797S, T790M-negative disease; however, because the evidence is derived from a single case and lacks validation by tissue rebiopsy, further confirmation in real- world cohorts and mechanistic studies is warranted (Table 1).

    Case Report: Short-term disease control with subsequent icotinib therapy in EGFR L858R/C797S, T790M-negative lung adenocarcinoma after osimertinib resistance · 2026 · DOI

  • The 2025 Stanford Lung Cancer Summit highlighted that healthcare providers still possess insufficient awareness of lung cancer in never-smokers, while standardized screening guidelines for this population remain lacking (36).

    Conditional dependence of the “male–SCC, female–ADC” teaching heuristic in lung cancer: shifts in exposure pathways and the need for pathology education reform · 2026 · DOI

  • For clinical practice: • Adopt a tiered testing strategy (IHC → RHSA → MRT-PCR) • Mandatory orthogonal confirmation for discordant clinical-molecular findings For health policy: • Enforce standardized tissue handling protocols (limiting cold ischemia time, formalin fixation duration) • Invest in training programs for RHSA and IHC interpretation 18 medRxiv preprint doi: https://doi.org/10.64898/2026.06.25.26356534; this version posted June 29, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

    Optimizing EGFR Mutation Testing in Resource-Limited Settings: A Comparative Analysis of Diagnostic Platforms in Libya · 2026 · DOI

  • Navigational Note: - Delusions - Death Moderate delusional symptoms Severe delusional symptoms; hospitalization not indicated; new onset Life-threatening consequences, threats of harm to self or others; hospitalization indicated Definition: A disorder characterized by false personal beliefs held contrary to reality, despite contradictory evidence and common sense.

    [Expert consensus on adverse events management of highly selective RET-TKIs (2026 edition)]. · 2026 · DOI

  • Future AI-assisted, multicenter, and prospective studies are warranted to validate these associations more robustly and to accelerate the integration of this approach into clinical practice, ultimately establishing PET/CT as an indispensable component of personalized oncologic therapy.

    Association between metabolic activity and molecular alterations in lung adenocarcinoma: Insights from 18F-FDG PET/CT · 2026 · DOI

  • Further studies with larger cohorts, longer follow-up, and integrated molecular anal- yses are warranted to better elucidate the clinical signifi- cance of this heterogeneity in EGFR-mutant NSCLC.

    Sensitivity of different epidermal growth factor receptor (EGFR) exon 19 deletion subtypes to first-line osimertinib in Chinese non-small cell lung cancer patients · 2026 · DOI

  • non-15n-del) have also yielded conflicting results regarding PFS and OS [10, 18, 22]. Collectively, these inconsistent findings highlight the ongoing controversy and underscore the need for further investigation, particularly with newer-generation TKIs. Limited studies either focused on osimertinib as second-line treatment, had insufficient sample sizes, or exclusively targeted spe- cific subtypes of rare mutations, lacking larger sample cohorts to explore the efficacy of first-line osimertinib in various EGFR 19del subtypes.

    Sensitivity of different epidermal growth factor receptor (EGFR) exon 19 deletion subtypes to first-line osimertinib in Chinese non-small cell lung cancer patients · 2026 · DOI

  • Following multidisciplinary team (MDT) assessment and adherence to a strict 6-week preoperative bevacizumab washout period (based on pharmacokinetic reasoning and NCCN guidelines, though prospective data are lacking), the patient underwent conversion from thoracoscopic to open right lower lobectomy with systematic lymph node dissection due to severe fibrosis and frozen hilar lymph nodes.

    Case Report: Successful conversion surgery following chemo-antiangiogenic therapy in a lung adenocarcinoma patient with active rheumatoid arthritis and rare EGFR mutation after immunotherapy-triggered flare · 2026 · DOI

  • IntroductionClonal hematopoiesis of indeterminate potential (CHIP) is a recognized risk factor for hematologic malignancies, but its contribution to different types of solid cancers remains incompletely defined.

    Gene-Specific Analysis of Clonal Hematopoiesis Identifies ASXL1 as a Risk Factor for Lung Cancer · 2026 · DOI

  • 8552 Background: Genomic activation of the WNT/β-catenin pathway via APC loss-of-function or activating CTNNB1 mutations is well established across multiple cancer types, but its prevalence and genomic context in non–small cell lung cancer (NSCLC) remain poorly characterized.

    Clinico-genomic landscape and prognostic impact of APC/CTNNB1 oncogenic alterations in non–small cell lung cancer. · 2026 · DOI

  • must be acknowledged to caution against premature generalization: (1) The single-case design inherently limits generalizability to broader populations and underscores the necessity of validation in larger, prospective studies. (2) The 36-month follow-up prevents assessment of long-term recurrence risks or delayed toxicities. (3) The resolution of Osi-ILD without corticosteroids may not generalize to severe cases requiring immunosuppression.

    Sequential almonertinib therapy following osimertinib-induced interstitial lung disease in early-stage EGFR-mutant lung adenocarcinoma: a case report · 2026 · DOI

  • The coordinated activation of PI3K-Akt and IL-17 inflammatory signaling pathways in ACTN1-high tumors requires mechanistic investigation to determine whether these pathways operate independently or synergistically in facilitating EMT, cell detachment, and metastatic colonization.

    Integrative single-cell and bulk RNA sequencing unravels the role of ACTN1 in promoting lung cancer with brain metastasis and epidermal growth factor receptor-tyrosine kinase inhibitor resistance · 2026 · DOI

  • Single-cell RNA sequencing studies of LCBM specimens are limited by potential biases and challenges in sample collection; expanding the analysis to incorporate a broader array of clinical specimens would strengthen the generalizability of ACTN1-related findings across patient populations.

    Integrative single-cell and bulk RNA sequencing unravels the role of ACTN1 in promoting lung cancer with brain metastasis and epidermal growth factor receptor-tyrosine kinase inhibitor resistance · 2026 · DOI

  • The downstream regulatory mechanisms and molecular associations between ACTN1 and epithelial-mesenchymal transition (EMT) require elucidation using advanced experimental methods beyond computational prediction to establish direct causal relationships in LCBM progression.

    Integrative single-cell and bulk RNA sequencing unravels the role of ACTN1 in promoting lung cancer with brain metastasis and epidermal growth factor receptor-tyrosine kinase inhibitor resistance · 2026 · DOI

  • The efficacy of specifically targeting ACTN1 to reverse EGFR-TKI resistance and treat lung cancer with brain metastasis (LCBM) has been validated only in osimertinib-resistant cell lines and requires large-scale clinical trials to demonstrate therapeutic effectiveness in patient populations.

    Integrative single-cell and bulk RNA sequencing unravels the role of ACTN1 in promoting lung cancer with brain metastasis and epidermal growth factor receptor-tyrosine kinase inhibitor resistance · 2026 · DOI

  • The clinical utility and potential interaction between GJB3 and ACTN1 in modulating EGFR-TKI sensitivity and immunotherapy response in LUAD require experimental validation to establish mechanistic linkage between this hub gene and ACTN1-driven drug resistance phenotypes.

    Integrative single-cell and bulk RNA sequencing unravels the role of ACTN1 in promoting lung cancer with brain metastasis and epidermal growth factor receptor-tyrosine kinase inhibitor resistance · 2026 · DOI

  • HER2-targeted therapy in non–small-cell lung cancer has rapidly evolved from an area of unmet clinical need to a field with multiple effective treatment options. The development of HER2-selective tyrosine kinase inhibitors and antibody–drug conjugates has substantially improved outcomes for patients with HER2-mutant NSCLC and established HER2 as a clinically actionable oncogenic driver. Despite these advances, several challenges remain. The optimal sequencing of HER2-targeted agents has not yet been defined, and prospective data are needed to clarify how best to integrate TKIs, ADCs, and other systemic therapies across treatment lines. Acquired resistance is expected to become increasingly relevant as improves, underscoring the importance of patient survival understanding resistance mechanisms and developing rational strategies to overcome them. In parallel, refinement of predictive biomarkers beyond HER2 mutation status may help better individualize treatment selection and avoid unnecessary toxicity.

    Evolving treatment strategies for HER2-altered non–small-cell lung cancer: the rise of TKIs and ADCs · 2026 · DOI

  • A significant treatment interaction was observed for EGFR–TKIs, with benefit limited to the high-sCD25 subgroup (HR, 0.

    Real-world evidence of baseline soluble CD25 as a prognostic biomarker and indicator of differential EGFR–TKI benefit in stage IV lung adenocarcinoma · 2026 · DOI

  • This analysis provided rationale for further research of larger datasets investigating therapeutic approaches in sqNSCLC, which may have significant implications for consensus guideline recommendations and routine clinical practice.

    The Impact of Smoking Status on the Genomic Landscape of Lung Squamous Cell Carcinoma · 2026 · DOI

  • The relationship between obesity and cancer, specifically the lung cancer has been studied by many researchers, and they have revealed a positive association of lung cancer with obese individuals, but the mechanism is still not completely understood.

    OBESITY AND LUNG CANCER (INVESTIGATING THE RELATIONSHIP) · 2023 · DOI

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54 open questions have been extracted from the limitations and future-work passages of 407 Lung Cancer Treatments and Mutations 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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