Open research questions in Cancer Research and Treatments
47 unresolved questions extracted from the limitations and future-work sections of 152 Cancer Research and Treatments papers in our library. Each links back to the study that raised it.
What the literature leaves open
The study highlights the challenges of characterizing the research landscape and knowledge base in a rapidly evolving field. The study notes the challenges of translating intratumoral microbiota research into clinical practice. The study emphasizes the need for rigorous and systematic approaches to bibliometric and visualization analyses.
Global research trends and emerging frontiers of intratumoral microbiota in cancer immunotherapy: a bibliometric and visualization analysis · 2026 · DOIThe paper identifies a gap in the understanding of the mechanisms by which Enterococcus modulates the immune system. It highlights the need for further research on the double-edged sword effect of Enterococcus on malignant tumor therapy.
The distinction between protumorigenic and antitumorigenic effects of Enterococcus depends on strain genotype, host immune status, and therapeutic intervention. The development of novel microbiome-based therapies is challenging due to the complexity of the gut microbiota. The double-edged sword effect of Enterococcus on malignant tumor therapy requires further research to fully understand.
Gut microbiota-derived metabolites have recently emerged as modulators of cancer immunometabolism, however, their role in PCa progression and immunotherapy is poorly understood.
Lactobacillus plantarum-derived indole-3-lactic acid inhibits prostate cancer progression through ASF1B/ENO1 axis and remodels the tumor microenvironment to enhance anti-PD-1 therapy · 2026 · DOIThe findings of our investigation lay a foundation for further research into the roles of tumor microbe-derived metabolites in cancer.
Genome Mining of the Tumor Microbiome Reveals Biosynthetic Diversity and Potential Tumor-modulating Metabolites · 2026 · DOIThe understanding of intratumoral microbiota is funda- mentally reshaping current views of gastrointestinal cancer biology. Tumor-associated microbes exhibit diverse origins, substantial inter-individual variability, and distinct organ- and tissue-specific distribution patterns. However, based on avail- able evidence, knowledge of intratumoral microbiota remains incomplete. This emerging field holds considerable promise but is also accompanied by significant challenges. Rational utilization of intratumoral microbiota may enable the devel- opment of new frameworks for early cancer diagnosis, multi- modal treatment strategies, and assessment of prognosis and therapeutic response, which represent central directions for future research. At present, many studies rely on relatively low-resolution detection approaches and limited sample sizes to character- ize disease-associated changes in intratumoral microbiota. As a result, conclusions drawn from such studies may not fully capture the true biological landscape. Future investigations should apply advanced technologies, including metagen- omic sequencing, spatial transcriptomics, and microbial in situ imaging, to achieve high-resolution and comprehensive profiling of intratumoral microbiota and the interactions with host cells in large-scale, multicenter cohorts. Many existing studies primarily describe associations between intratumoral microbiota composition and clini- cal phenotypes or outcomes, while underlying mechanisms remain largely unexplored. Future work should integrate experimental models, such as organoids and xenograft sys- tems with germ-free animals, to mechanistically define how specific microbes or the components drive tumorigenesis, immune modulation or evasion, and therapy resistance. Such approaches will be essential for identifying concrete molecular mechanisms and actionable therapeutic targets. The ultimate objective is to develop precise and personal- ized therapies targeting intratumoral microbiota. With deeper functional insight into intratumoral microbial activity, a new generation of precision microecologic therapies may emerge. Potential strategies include engineered phages designed to selectively eliminate pro-carcinogenic bacteria, as well as bac- teria-drug combination therapies aimed at reversing treat- ment resistance through microbiota modulation. In addition, intratumoral microbiota shows promise as a biomarker for predicting therapeutic response and guiding patient stratifica- tion. Nevertheless, translation of these approaches into clini- cal practice will require high-quality prospective studies with larger cohorts and extended follow-up periods.
Tumor-resident bacteria in gastrointestinal cancers: from regulatory mechanisms to clinical implications · 2026 · DOIWhile the bacterial microbiome is a recognized modulator of the tumor microenvironment (TME), the non-bacterial oncobiome, comprising the mycobiome (fungi) and virome (viruses), represents a critical but under-explored frontier in cellular adaptability.
Results have remained inconsistent, possibly due to differences in metabolic adaptations across molecular breast cancer subtypes. Gene expression does not necessarily correlate directly to protein expression.
Current evidence remains limited by small studies, heterogeneous endpoints, and insufficient long-term follow-up. The evolution and timeline of major discoveries for living cancer therapeutics are not fully understood.
Oncobiotics in urinary bladder cancer. A narrative review of living cancer therapeutics · 2026 · DOIThere is a need for innovative therapeutic strategies to overcome the limitations of conventional cancer therapies. The current evidence on living cancer therapeutics in urinary bladder cancer is limited by small studies and heterogeneous endpoints.
Oncobiotics in urinary bladder cancer. A narrative review of living cancer therapeutics · 2026 · DOIInvestigation of the mechanisms underlying the associations between microbial and metabolic changes and treatment response and toxicity - Development of personalized medicine approaches based on individual microbiome and metabolome profiles
Fecal microbiome and metabolome dynamics during immunotherapy-based total neoadjuvant therapy in rectal cancer: associations with treatment response and toxicity · 2026 · DOILimited understanding of the dynamics of the fecal microbiome and metabolome during iTNT - Need for non-invasive biomarkers and functional clues for optimizing iTNT
Fecal microbiome and metabolome dynamics during immunotherapy-based total neoadjuvant therapy in rectal cancer: associations with treatment response and toxicity · 2026 · DOIInvestigation of the mechanisms by which the microbiome regulates MHC-II expression in colon cancer cells. Development of novel therapies that target the microbiome to enhance anti-tumor immunity. Exploration of the applicability of the study's approach to other types of cancer.
Microbial induction of MHC-II expression in colon cancer cells overcomes immunotherapy resistance and limits metastasis · 2026 · DOIThe lack of understanding of the mechanisms that convert poorly inflamed tumors into lesions capable of supporting productive antitumor immunity. The need to identify novel approaches to sensitize microsatellite-stable colorectal cancer to immune checkpoint blockade immunotherapy.
Microbial induction of MHC-II expression in colon cancer cells overcomes immunotherapy resistance and limits metastasis · 2026 · DOIThe prognosis and quality of life for patients with advanced disease remain suboptimal. Current treatment strategies have limitations, and new approaches are needed.
Phytochemicals remodel antitumor immunity via the “microbiota–metabolite–receptor” axis: focus on colorectal cancer and immunotherapy · 2026 · DOIThe current treatment strategies for CRC have limitations, and new approaches are needed. The role of phytochemicals in remodeling antitumor immunity via the microbiota-metabolite-receptor axis is not fully understood.
Phytochemicals remodel antitumor immunity via the “microbiota–metabolite–receptor” axis: focus on colorectal cancer and immunotherapy · 2026 · DOIexploration of microbiota-directed interventions, - development of adoptive cell therapies based on innate immune cells, - investigation of the potential context-dependent roles of SOCS1.
Gastrointestinal acute graft versus host disease: a translational perspective from pathogenesis to precision prevention and treatment · 2026 · DOIThe need for a better understanding of the effects of microbiome-derived metabolites on host physiology. The need for standardized methods for analyzing and interpreting microbiome data. The need for further research on the potential therapeutic applications of microbiome-derived metabolites.
Microbiome-derived bioactive molecules regulate host signaling and therapeutic responses in cancer and metabolic diseases · 2026 · DOIMechanistic studies should connect tumor-intrinsic signaling to immune, stromal, metabolic, and stress-response programs. Biomarker development should progress from single-gene markers to multidimensional signatures. Emerging approaches to TME remodeling and precision treatment should be further developed.
Editorial: Progress in molecular mechanisms and targeted therapies for solid tumor microenvironments · 2026 · DOIThe interactions between tumor-intrinsic alterations and stromal, immune, metabolic, and stress-response programs are not well understood. Prior work has focused on individual signaling pathways, but a more holistic approach is needed.
Editorial: Progress in molecular mechanisms and targeted therapies for solid tumor microenvironments · 2026 · DOIThe evidence is not yet strong enough to support the sweeping claim that bacteria are stable and biologically decisive constituents across cancers in general. The study acknowledges that the data remain primarily associative and should be described at the threshold they actually reach.
The effort to establish more effective cancer prevention and diagnosis methods is complicated by ethical and accessibility challenges. Sophisticated animal models are needed to provide more preclinical evidence.
Sophisticated animal models are needed to provide more preclinical evidence. Interdisciplinary approaches are necessary to quantitatively understand the relationship between microbes in tumours and tumour formation and development.
Doxazosin is known to inhibit cell migration and invasion in several cancer cell types; however, the precise mechanisms underlying doxazosin’s anticancer effects in TNBC have not been fully elucidated.
Abstract 4037: Doxazosin exerts anti-metastatic potential in triple-negative breast cancer via impairment of cancer stem-like features · 2023 · DOIHowever, its causal relationship with immunotherapeutic efficacy remains unclear, which promoted us to explore if and how probiotic Lacticaseibacillus rhamnosus Probio-M9 manipulates gut microbiome for expected outcomes.
Lacticaseibacillus rhamnosus Probio-M9 enhanced the antitumor response to anti-PD-1 therapy by modulating intestinal metabolites · 2023 · DOI
Most-cited papers in Cancer Research and Treatments
- Commensal <i>Bifidobacterium</i> promotes antitumor immunity and facilitates anti–PD-L1 efficacy · Science · 2015 · 3,503 citations
- Intratumoural microbiota: a new frontier in cancer development and therapy · Signal Transduction and Targeted Therapy · 2024 · 205 citations
- <i>Fusobacterium nucleatum</i> and cancer · Periodontology 2000 · 2022 · 174 citations
- Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia · Nature Communications · 2024 · 166 citations
- Probiotic neoantigen delivery vectors for precision cancer immunotherapy · Nature · 2024 · 158 citations
- Folate Receptor Alpha—A Novel Approach to Cancer Therapy · International Journal of Molecular Sciences · 2024 · 104 citations
- Peptostreptococcus anaerobius mediates anti-PD1 therapy resistance and exacerbates colorectal cancer via myeloid-derived suppressor cells in mice · Nature Microbiology · 2024 · 101 citations
- Promising dawn in tumor microenvironment therapy: engineering oral bacteria · International Journal of Oral Science · 2024 · 92 citations
- Colibactin-driven colon cancer requires adhesin-mediated epithelial binding · Nature · 2024 · 69 citations
- Campylobacter jejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis · Cell Host & Microbe · 2024 · 48 citations
Most recent work
- Local gene editing of fibroblasts in tumors reveals a new cancer-associated fibroblast state · The Journal of Experimental Medicine · 2026
- Genome-resolved metagenomics of the tumour microbiome: From strain diversity to functional cancer ecology · Pathology - Research and Practice · 2026
- Carboxylesterase 2-Engineered Stem Cell Therapy Shows Superior Efficacy over Cytosine Deaminase in Castration-Resistant Prostate Cancer · Biomedicines · 2026
- Abstract 4889: Distinct tumor microbiome profiles in triple negative breast cancer compared to other breast cancer subtypes: A pilot study · Cancer Research · 2026
- A novel recombinant arginine deiminase from Limosilactobacillus reuteri DSM 20016 demonstrates anticancer activity against colon cancer cells · Molecular Biology Reports · 2026
- An Endoplasmic Reticulum-Anchored Bioorthogonal Therapeutic System Induces Visualized ER Stress in Tumor Cells · CCS Chemistry · 2026
- Tumor-resident bacteria in gastrointestinal cancers: from regulatory mechanisms to clinical implications · Cancer Biology & Medicine · 2026
- The interaction between microbes and cytokines in cancer: unraveling the underlying effects · Journal of Translational Medicine · 2026
- Living Microbial Drugs · Chemistry – A European Journal · 2026
- Tumor-targeted aptamer-conjugated engineered bacteria for CXCL9 cytokine delivery in non-small cell lung cancer immunotherapy · Journal of Translational Medicine · 2026
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