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Open research questions in Cancer-related Molecular Pathways

143 gap statements mined from Cancer-related Molecular Pathways papers in our 4.5M-paper local library, which holds 630 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Structure-based analysis of MDM4 in p53- and MDM2- independent context has not yet been fully characterized. Importantly, the role of MDM4 in cancer immunity remains poorly understood.

    MDM4 at the Crossroads: Beyond p53 and MDM2 · 2026 · DOI

  • A limitation of this study is the absence of re-docking or selectivity validation against additional CDK family members, which may be addressed in future studies to further refine the binding specificity.

    Transcriptomics-driven identification of CDK1 as a central oncogenic driver in TNBC: an in silico structural modeling and MD simulation approach · 2026 · DOI

  • There is a need to understand the mutational profile of the TP53 gene in OSCC. There is a need to evaluate the functional impact of the identified mutations.

    NGS mutation Profiling of TP53 gene analysis in Oral Squamous Cell Carcinoma (OSCC) · 2026 · DOI

  • The genetic basis of SHFM is not fully understood. The study identifies a novel TP63 variant associated with SHFM and tooth agenesis, highlighting the importance of further research into the genetic causes of the condition.

    Identification of novel tumor protein 63 variant associated with split-hand/foot malformation and tooth agenesis · 2026 · DOI

  • The study only examines the impact of increased expression of TAp73a and ΔNp73a isoforms on global DNA methylation in SaOS-2 cells. The study does not investigate the mechanisms underlying the lack of significant impact on DNA methylation.

    The effect of p73 isoforms on DNA methylation in human osteosarcoma cells · 2026 · DOI

  • Future studies may investigate the mechanisms underlying the lack of significant impact on DNA methylation. Future research may examine the role of p73 isoforms in regulating DNA methylation in other types of cancer. Future studies may explore the therapeutic potential of targeting p73 isoforms in human osteosarcoma.

    The effect of p73 isoforms on DNA methylation in human osteosarcoma cells · 2026 · DOI

  • The role of E2F6 in CRC remains controversial and not fully understood. The molecular mechanisms underlying CRC pathogenesis are complex and not fully elucidated. There is a need for further studies to investigate the expression and function of E2F6 in CRC.

    Elevated E2F6 Expression in Colorectal Cancer Tissues and Its Association With Clinicopathological Features · 2026 · DOI

  • There is a lack of specific guidelines for cancer surveillance and management in individuals with TP53 post-zygotic mosaicism. There is a need for further research on the clinical implications of TP53 post-zygotic mosaicism.

    Mosaic TP53 pathogenic variant in early-onset breast cancer: a case report · 2026 · DOI

  • The study highlights the need for further research into the clinical expression of germline TP53 variant carriers, including the use of multigene panel testing and functional classification of TP53 variants.

    Genotypic and phenotypic characteristics of germline TP53 variant carriers: experience from two cancer genetic counseling units · 2026 · DOI

  • The study notes that chromosomal instability is associated with a poorer prognosis in sporadic CRC. The study highlights the need to characterize TP53 variants in a Mexican cohort of patients with CRC. The study references the challenge of interpreting the biological significance of TP53 variants.

    Molecular Characterization of TP53 Variants in Exons 4-8 and p53 Immunoexpression in a Mexican Colorectal Cancer Cohort · 2026 · DOI

  • The expression of the p53 protein is not fully understood. The impact of the p53 protein on the expression of the transcription factor E2F in the CycD/Cdk4(6) subsystem is not well-studied.

    A mathematical perspective into the p53 protein on the expression of the transcription factor E2F in CycD/Cdk4(6) subsystem · 2026 · DOI

  • The mechanisms of apoptosis induction by CDK inhibitors are not fully understood. The specific CDKs involved in apoptosis induction are not well characterized.

    Inhibition of RNA polymerase II-activating CDK9 and CDK12/13, but not of cell cycle relevant CDKs, induces apoptosis by downregulating the short-lived Bcl-2 proteins Mcl1 and Bfl1/A1 · 2026 · DOI

  • While genetic knockout studies suggest roles for HIPK4 in spermiogenesis and cutaneous squamous cell carcinoma, whether these cellular functions can be recapitulated by pharmacological inhibition remains to be determined.

    Macrocyclization of Broad-Spectrum Kinase Inhibitor Bosutinib leads to Potent and Selective Quinoline-based HIPK4 Inhibitor AZ137 · 2026 · DOI

  • Further studies are needed to fully elucidate the molecular mechanisms underlying glioma stem cell biology. The development of therapeutic strategies targeting glioma stem cells is an area of ongoing research. The identification of potential therapeutic targets, such as RAD51 and the EDN3-EDNRB axis, could lead to the development of more effective treatments.

    Molecular insights into DNA damage response plasticity in glioma stem cells · 2026 · DOI

  • There is a need to better understand the molecular mechanisms underlying glioma stem cell biology. Current therapies provide only modest survival benefits, and there is a need to develop more effective treatments.

    Molecular insights into DNA damage response plasticity in glioma stem cells · 2026 · DOI

  • Further studies are needed to investigate the therapeutic potential of targeting BRD4 in gastric cancer. The development of new strategies for targeting BRD4 is an area of future research. The study's findings may have implications for the development of new treatments for other diseases.

    Targeting BRD4 in gastric cancer: promoting apoptosis and suppressing tumor progression · 2026 · DOI

  • The underlying mechanisms of the pathogenesis and progression of gastric cancer are largely unknown. The downstream targets of RUNX2 are rarely explored in GC cells.

    RUNX2 influences alternative splicing of genes associated with gastric cancer progression by regulating SF3B6 expression in HGC-27 cells · 2026 · DOI

  • The early pre-malignant events that lead to TNBC remain elusive, largely due to a lack of tractable models that recapitulate stepwise tumor initiation in a natural tissue context.

    Abstract P10: Early Immunosuppressive Landscape Shaped by BRCA1/p53 Loss in Early Pre-Malignant Mammary Glands Permits Tumor Development · 2026 · DOI

  • In particular, whether hypoxia, chronic inflammatory signaling, or other microenvironment-derived cues contribute to USP25 upregulation in breast cancer warrants further investigation.

    The deubiquitinase USP25 contributes to stemness and malignant progression of breast cancer by stabilizing C1ql4 · 2026 · DOI

  • However, the genes and pathways involved in tumor suppres‑ sion following TM6SF2 overexpression in HCC cells remain unclear. Few studies have examined the mechanisms by which TM6SF2 contributes to hepato‑ carcinogenesis or the downstream regulatory pathways it modulates.

    TM6SF2 overexpression suppresses the proliferation and promotes apoptosis of human hepatocellular carcinoma cells · 2026 · DOI

  • Further studies are needed to investigate the clinical significance of the p53 R280S mutation in HCC. Further research is needed to develop therapeutic strategies targeting the p53 R280S mutation. Further studies are needed to explore the role of p53 mutations in drug resistance in other types of cancer.

    p53-R280S mutation confers lenvatinib resistance in hepatocellular carcinoma via Bcl-2-mediated anti-apoptotic signaling · 2026 · DOI

  • The underlying mechanisms of lenvatinib resistance in HCC are not fully understood. The role of p53 mutations in lenvatinib resistance in HCC is not well characterized.

    p53-R280S mutation confers lenvatinib resistance in hepatocellular carcinoma via Bcl-2-mediated anti-apoptotic signaling · 2026 · DOI

  • Future studies should investigate the mechanisms underlying the relationship between FGFR4 and APOBEC3 activity. The development of novel biomarkers for the classification of the HER2E subtype should be explored. Alternative models for human breast cancer should be developed to overcome the limitations of existing models.

    FGFR4-associated APOBEC3 mutagenesis characterizes HER2-enriched subtype of human breast cancer · 2026 · DOI

  • The study only analyzed a Mexican cohort, - The sample size was limited to 142 patients, - Only exons 4-8 of TP53…

    Molecular Characterization of TP53 Variants in Exons 4-8 and p53 Immunoexpression in a Mexican Colorectal Cancer Cohort · 2026 · DOI

  • Developing treatments that aim to manage and control oncogenic activities - Investigating the operating conditions and response to stimuli in different human body tissues - Examining the impact of other inhibitors on cell growth…

    A mathematical perspective into the p53 protein on the expression of the transcription factor E2F in CycD/Cdk4(6) subsystem · 2026 · DOI

Most-cited papers in Cancer-related Molecular Pathways

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Open questions raised by papers listed on this page include: (1) Structure-based analysis of MDM4 in p53- and MDM2- independent context has not yet been fully characterized (“MDM4 at the Crossroads: Beyond p53 and MDM2”, 2026); (2) There is a need to understand the mutational profile of the TP53 gene in OSCC (“NGS mutation Profiling of TP53 gene analysis in Oral Squamous Cell Carcinoma…”, 2026); (3) The study does not investigate the mechanisms underlying the lack of significant impact on DNA methylation (“The effect of p73 isoforms on DNA methylation in human osteosarcoma cells”, 2026); (4) The role of E2F6 in CRC remains controversial and not fully understood (“Elevated E2F6 Expression in Colorectal Cancer Tissues and Its Association With…”, 2026); (5) There is a lack of specific guidelines for cancer surveillance and management in individuals with TP53 post-zygotic mosaicism (“Mosaic TP53 pathogenic variant in early-onset breast cancer: a case report”, 2026). 143 gap statements have been mined from Cancer-related Molecular Pathways papers in our 4.5M-paper local library, which holds 630 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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