Open research questions in Cancer-related molecular mechanisms research
784 gap statements mined from Cancer-related molecular mechanisms research papers in our 7.9M-paper local library, which holds 2,670 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
Direct evidence linking GAS6‑AS1 to immune‑cell infiltration, immune evasion or immunotherapy response remains limited and warrants further investigation. Recent studies further highlight that cancer‑associated lncRNAs function within complex and multilayered regula‑ tory networks rather than through isolated linear pathways.
Late-stage diagnoses and therapy resistance remain significant challenges in female-related cancers. The complex and multifactorial pathogenesis of gynecologic cancers poses a challenge for diagnosis and treatment. Identifying novel molecular targets and biomarkers is essential to address these challenges.
LncRNA CCAT2 role in female-related cancer progression and diagnosis: a comprehensive review · 2026 · DOILong-term survival rates for AML patients remain suboptimal, particularly among elderly patients and those with relapsed or refractory disease. The molecular mechanism of AML is complex and not fully understood. Finding new therapeutic targets for AML is challenging.
LncRNA SNHG25 promotes proliferation, migration, and invasion of acute myeloid leukemia by competitively binding to miR-205-5p · 2026 · DOIThe function of lncRNA SNHG25 in acute myeloid leukemia remains unclear. The molecular mechanism of AML and new therapeutic targets need to be explored.
LncRNA SNHG25 promotes proliferation, migration, and invasion of acute myeloid leukemia by competitively binding to miR-205-5p · 2026 · DOIFuture studies should define how these regulatory modes are coordinated under physiological and pathological conditions and determine whether specific lncRNA–protein interfaces can be selectively targeted to modulate innate immunity without broadly disrupting the functions of their associated proteins. Therapeutically, these mechanisms suggest several levels of intervention.
LncRNA–protein interactions: molecular switches for the precise regulation of innate immunity · 2026 · DOIPreliminary experiments suggest it may play a role in neovascularization, although the precise mechanism and its potential as a therapeutic target for DR remain to be explored. ATP2B2-IT2 showed potential relevance based on the exploratory SHAP analysis; however, its biological function and underlying mechanisms remain unclear and require further investigation.
Identification of novel lncRNAs potentially associated with diabetic retinopathy based on machine learning prediction · 2026 · DOICommonly used biomarkers, including alpha‑fetoprotein, carcinoem‑ bryonic antigen (CEA), carbohydrate antigen (CA)19‑9, human epidermal growth factor receptor 2 and programmed death‑ligand 1 (PD‑L1), provide clinical value in selected cancer types but remain limited by inadequate sensitivity, high false‑positive rates and inconsistent prognostic perfor‑ mance.
Comprehensive landscape and future perspectives of PIWI‑interacting RNAs in cancer (Review) · 2026 · DOIWhile the precise contribution of IL-6 within this system remains unclear, its increased expression may represent a compensatory cellular response to oxidative stress and ferroptosis sensitization.
Long Non-Coding RNA LINC01614 Promotes Aggressive Phenotypes and Ferroptosis Resistance in Papillary Thyroid Cancer Through a Putative miR-4521/IGF2/PI3K-AKT Signaling Axis · 2026 · DOIFuture research should move beyond descriptive transcriptomic studies toward mechanistic, translational, and clinically oriented investigations.
While recognized as a key mediator of treatment resistance in DLBCL, the molecular underpinnings of RTX resistance remain incompletely characterized39.
lncRNA SNHG29-RPS-CYLD axis is mitochondrially localized and mediates apoptosis in rituximab-resistant DLBCL · 2026 · DOIFor human-specific lncRNAs, conservation of sequence, expression, interacting partners, and function should be evaluated separately. Complementary testing in human tumor models, relevant immune or stromal co-cultures, and normal human tissue models would help address limitations that cannot be resolved by a single experimental system.
Long non-coding RNA-mediated stress adaptation and immune remodeling in non-small cell lung cancer: molecular mechanisms and therapeutic implications · 2026 · DOIThe molecular mechanism of gastric cancer MDR remains unclear. The role of LINC00657 and miR-218-2-3p in gastric cancer chemoresistance is unknown. The relationship between miR-218-2-3p and cyclin D1 in gastric cancer MDR is not well understood.
Long intergenic non-protein coding RNA 00657/miR-218-2-3p/cyclin D1 axis drives gastric cancer chemoresistance · 2026 · DOILncRNAs, traditionally characterized by their non-coding nature, have not been thoroughly explored for their potential coding roles. They harbor sORFs capable of encoding peptides, as well as numerous microproteins that possess secondary structures and can undergo conformational changes.
Beyond the Transcript: Translating Non-Coding RNAs and Their Impact on Cellular Regulation · 2025 · DOIIn spite of its likely importance in cellular physiology, the role of C328 in cancer progression and in determining the cancer stem cell phenotype has not been investigated before.
A single cysteine residue in vimentin regulates long non-coding RNA XIST to suppress epithelial–mesenchymal transition and stemness in breast cancer · 2025 · DOIIntroduction Increasing evidence indicates that long non‑coding RNAs (lncRNAs) play diverse roles in multiple stages of normal cellular biology and pathological processes (1). LncRNAs are transcripts exceeding 200 nucleotides in length that cannot encode proteins due to the absence of open reading frames (2).
KRAS remains one of the most challenging yet promising therapeutic targets in NSCLC. Growing knowledge of KRAS-dependent signalling networks, mutation-specific biology, epigenetic regulation, and post-translational modifications has substantially improved our understanding of tumour development and therapeutic vulnerabilities. The emergence of selective KRAS inhibitors has transformed the treatment landscape.
The Role of KRAS in Non-Small Cell Lung Cancer: From Molecular Background to Precision Medicine · 2026 · DOIAdvances propelled by the Human Genome Project, together with rapid progress in high‑throughput technologies, have characterised numerous piRNAs with previously undefined functions. Evidence suggests that piRNAs contribute to tumour initiation and progression by regulating key molecules and downstream signalling pathways through epigenetic, transcriptional and post‑transcriptional mechanisms.
Comprehensive landscape and future perspectives of PIWI‑interacting RNAs in cancer (Review) · 2026 · DOIFinally, the functional relationship between TGCB, CHASERR, and CHD2 is not yet defined, and mechanistic studies will be required to determine whether TGCB contributes directly to CHD2 dosage control or to broader processes.
The progression from MASLd to Hcc is a complex, multifac‑ torial pathological process driven by the interplay of metabolic dysregulation, chronic inflammation, oxidative stress, immune dysfunction and gut microbiota imbalance. The present review systematically highlights the central regulatory roles of ncRNAs, including miRNAs, lncRNAs and circRNAs, across this disease continuum.
Emerging role of non‑coding RNAs in the progression of MASLD‑driven hepatocellular carcinoma (Review) · 2026 · DOIIntroduction Metabolic dysfunction‑associated steatotic liver disease (MASLd), affecting ~25% of the global population, is one of the most prevalent chronic liver diseases and is closely associated with metabolic dysregulation.
Emerging role of non‑coding RNAs in the progression of MASLD‑driven hepatocellular carcinoma (Review) · 2026 · DOIOn the one hand, available detection methods are still not sensitive enough to provide reliable results on ncRNA expression—especially in the case of cf-ncRNAs—which makes standardization difficult for routine diagnostics.
The role of lncRNAs in CSCs, chemoresistance, and metastasis has been widely investigated in the past decade. By regulating gene expression through interaction with DNA, RNA, and proteins, lncRNAs play key roles in the regulation of tumor EMP via diverse signaling pathways, thereby modulating cancer stemness and tumor progression.
Long Non-Coding RNAs: Key Regulators of Tumor Epithelial/Mesenchymal Plasticity and Cancer Stemness · 2025 · DOIMany of the ncRNAs described in this review have been shown to be involved in other conditions, both cardiac-related and non-cardiac-related diseases. For example, the lncRNA PVT1 has been shown to promote gallbladder cancer progression by targeting miR-18b-5p. miR-107 has been shown to partake in Alzheimer’s disease through regulating amyloid-β levels.
Investigating the role of CCAT2 in other types of cancer, - Elucidating the underlying molecular mechanisms of CCAT2 in female-related cancers, - Exploring the potential of CCAT2 as a therapeutic…
LncRNA CCAT2 role in female-related cancer progression and diagnosis: a comprehensive review · 2026 · DOIIn conclusion, our study establishes cscRNAs as functionally relevant contributors to gastric cancer pathogenesis and identifies exploratory associations with tumor immune microenvironment features, positioning cscRNA‐based signatures as promising candidate biomarkers for risk stratification and motivating further investigation of cscRNA–immune interactions.
Cross‐Strand Chimeric RNA Signature Predicts Prognosis and Identifies Tumor Immune Microenvironment Associations in Gastric Cancer · 2026 · DOI
Most-cited papers in Cancer-related molecular mechanisms research
- Landscape of transcription in human cells · Nature · 2012 · 4,556 citations
- Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis · Nature · 2010 · 4,430 citations
- RNA velocity of single cells · Nature · 2018 · 4,301 citations
- Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals · Nature · 2009 · 3,552 citations
- The landscape of long noncoding RNAs in the human transcriptome · Nature Genetics · 2015 · 2,407 citations
- UALCAN: An update to the integrated cancer data analysis platform · Neoplasia · 2022 · 2,224 citations
- RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription · Science · 2007 · 2,163 citations
- Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA · Nature · 2000 · 2,018 citations
- RNA-mediated epigenetic regulation of gene expression · Nature Reviews Genetics · 2015 · 1,006 citations
- Machine learning-based integration develops an immune-derived lncRNA signature for improving outcomes in colorectal cancer · Nature Communications · 2022 · 708 citations
Most recent work
- HiGLDP: a hierarchical graph neural network for predicting lncRNA-disease associations through multi-omic integration · BMC Biology · 2026
- Accurate isoform quantification in bulk and single-cell RNA-seq by integrating multi-platform sequencing data and sequence-to-expression models · bioRxiv · 2026
- The long noncoding RNA AC093895.1 promotes ovarian cancer formation and metastasis through a positive feedback network dependent on the transcription factor SOX4 · Cell Death and Disease · 2026
- Long non-coding RNA TTN-AS1 promotes acute liver injury in sepsis: A novel potential monitoring and therapeutic target · European Journal of Pharmacology · 2026
- Genetic variation reveals a homeotic long noncoding RNA that modulates human hematopoietic stem cells · Cell · 2026
- BRRIAR lncRNA alters breast cancer risk by modulating interferon signaling in cis and in trans · Molecular Cancer · 2026
- Cisplatin disrupts OCT1-DNMT1-piRNA epigenetic regulatory axis to suppress GAB2-mediated aggressiveness in OSCC · Archives of Biochemistry and Biophysics · 2026
- Multi-layered gene regulation by long non-coding RNAs: from chromatin to genome architecture · BMB Reports · 2026
- SNP calling, haplotype phasing and allele-specific analysis with long RNA-seq reads · Nature Methods · 2026
- HpMiX: A Disease ceRNA biomarker prediction framework driven by graph topology-constrained Mixup and hypergraph residual enhancement · Neural Networks · 2026
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