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Open research questions in Colorectal Cancer Treatments and Studies

128 gap statements mined from Colorectal Cancer Treatments and Studies papers in our 4.5M-paper local library, which holds 750 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

  • The study used a limited number of cell lines and xenograft models. The mechanisms underlying EHMT2-mediated 5-FU resistance may be complex and involve multiple factors.

    Targeting EHMT2 overcomes 5-fluorouracil resistance in colorectal cancer by modulating cell cycle and apoptosis · 2026 · DOI

  • The mechanisms underlying 5-FU resistance in CRC are not fully understood. The role of EHMT2 in 5-FU resistance has not been fully explored.

    Targeting EHMT2 overcomes 5-fluorouracil resistance in colorectal cancer by modulating cell cycle and apoptosis · 2026 · DOI

  • In the previous cohort study on CRLM conducted by our team, it was observed that integrated Chinese and Western medicine (ICWM) may offer advantages in treating CRLM, but high-level evidence is still lacking.

    Integrated Chinese and Western medicine prolong survival in colorectal cancer with liver metastasis: A retrospective cohort study · 2026 · DOI

  • There is limited evidence for the efficacy and safety of sorafenib therapy for advanced RCC in Japanese patients. The study aims to address this gap by analyzing data from daily clinical settings.

    Unveiling VARS1: a key driver of colorectal cancer progression and immune modulation · 2026 · DOI

  • Limited understanding of the predictors of chemotherapeutic efficacy in colon cancer.

    Predictive Value of Serum Trace Elements for Chemotherapeutic Efficacy in Gastric and Colon Cancer: A Cross-Sectional Study · 2026 · DOI

  • There is a need to identify reliable predictors of chemotherapeutic efficacy in colon cancer. The study addresses this gap by investigating the predictive value of baseline serum trace elements.

    Predictive Value of Serum Trace Elements for Chemotherapeutic Efficacy in Gastric and Colon Cancer: A Cross-Sectional Study · 2026 · DOI

  • The study has a limited sample size. The study only includes patients with RAS wild-type mCRC.

    Real-world practices in RAS wild-type metastatic colorectal cancer patients treated with targeted agents in the first-line a nationwide onco-colon Turkey registry · 2026 · DOI

  • There is a lack of real-world evidence on the efficacy of anti-EGFR agents in patients with RAS wild-type mCRC. Prior studies have primarily focused on clinical trials, and there is a need for real-world data.

    Real-world practices in RAS wild-type metastatic colorectal cancer patients treated with targeted agents in the first-line a nationwide onco-colon Turkey registry · 2026 · DOI

  • There is a need for novel approaches for the prevention and treatment of colorectal cancer. The molecular mechanisms associated with the combination treatment are not fully understood.

    Enhanced antitumor efficacy of sulfasalazine and mesalazine in colorectal cancer through modulatory action of Lacticaseibacillus rhamnosus GG · 2026 · DOI

  • How activated STAT3 in turn suppresses RBMS3 transcription remains to be fully elucidated; STAT3 is known to bind promoter regions of tumor suppressor genes and to recruit epigenetic repressors including DNMT3A and EZH2 to silence their expression.

    RBMS3 promotes ferroptosis in colorectal cancer and is suppressed by M2 tumor-associated macrophages via STAT3 activation · 2026 · DOI

  • Limited understanding of the molecular profiles of colorectal cancer liver metastases.

    Higher frequency of subclonal anti-EGFR resistance mutations in post-treatment samples from patients with colorectal cancer liver metastases following anti-EGFR-based conversion chemotherapy · 2026 · DOI

  • Although we found the strongest effects of HOM in young adulthood, future research is warranted to study NSCLC patients in adolescents or even pediatric NSCLC patient samples to fully reveal the role of HOM.

    Holistic oncologic management improves quality of life in driver gene negative advanced NSCLC a latent growth curve modeling study · 2026 · DOI

  • The specific impact of TAMs and their PD-L1 expression on post-treatment resistance and prognosis remains unclear. The spatial distribution and immunophenotypic characteristics of CD68+CD163+ M2-like TAMs and their association with post-treatment resistance and survival are not well understood.

    Association of intratumoral CD68+CD163+ M2-like macrophages with survival in metastatic colorectal cancer treated with chemotherapy plus bevacizumab · 2026 · DOI

  • The diagnostic role of CA 19-9 as a test for the detection of colorectal malignancy remains poorly defined because, as in other diagnostic modalities, the utility of CA 19-9 has several confounding limitations such as false-positive elevations in many benign conditions.

    Clinical Utility of Serum CA 19-9 Level in Colorectal Carcinoma Patients With Normal Serum Carcinoembryonic Antigen Levels: Correlation With Clinicopathological Features and Survival Outcomes · 2026 · DOI

  • The immune-related function of miR-6882-3p also remains unclear and needs further investigation. Whether circ_0027446 accelerates CRC progression through miRNA regulation had not been previously characterized.

    Circ_0027446: a novel biomarker and therapeutic target to combat colorectal cancer and enhance immune response · 2026 · DOI

  • The significance of specific mutation variants, particularly rare ones, in patients with colorectal cancer (CRC) and isolated liver metastases is insufficiently studied, while the possibility of achieving resectability is critical in the context of prognosis and survival.

    Prognostic significance of KRAS, NRAS, and BRAF mutations in patients with colorectal cancer and liver metastases: results of a single-center retrospective study · 2026 · DOI

  • There is a lack of studies on treatment delays among CRC patients in Uganda. The factors associated with treatment delay among CRC patients in Uganda are not well understood.

    Prevalence and factors associated with treatment delay among colorectal cancer patients at Mulago National Referral Hospital and the Uganda Cancer Institute: A cross-sectional study · 2026 · DOI

  • Finally, the analysis was conducted from the perspective of the Chinese healthcare system and may not be generalizable to other healthcare settings. Further comparative clinical and economic studies are warranted to better define the value of EGFR-targeted biosimilars in metastatic colorectal cancer.

    Economic evaluation of newly approved cetuximab biosimilars for first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer in China · 2026 · DOI

  • The precise role of UBC9 in colorectal cancer remains poorly understood. The exact mechanism and biological functions of UBC9 remain incompletely understood.

    UBC9 and PI3K Expression in Colorectal Cancer: Possible Prognostic Role · 2026 · DOI

  • There is a lack of direct comparisons between different therapeutic options. There is a need for more data on the sequence of tyrosine kinase inhibitors.

    Options for the third and subsequent lines of drug treatment for patients with metastatic colorectal cancer. A review · 2026 · DOI

  • Although recent work in gastric cancer highlighted the immunoregulatory and prognostic relevance of ITPRIPL1, it remains unclear whether such effects are conserved across anatomically related gastrointestinal malignancies or are restricted to specific tumor contexts(43).

    ITPRIPL1: A tumor immune-associated biomarker with prognostic and therapeutic implications in gastrointestinal cancer · 2026 · DOI

  • The incremental value of metabolomics for colorectal cancer risk prediction beyond clinical factors and polygenic risk scores is uncertain. Prior studies have not integrated metabolomics, clinical factors, and genetic risk for colorectal cancer risk prediction.

    Integrating metabolomics, clinical factors, and genetic risk for colorectal cancer risk prediction: Model development and internal-external cross-validation · 2026 · DOI

  • Although free oxaliplatin concentrations in such patients have been examined, few studies have conducted detailed pharmacokinetic profiling beyond day 1.

    Pharmacokinetic and pharmacogenomic profile of capecitabine and oxaliplatin in a patient with gastric cancer undergoing hemodialysis: a case report · 2026 · DOI

  • The study had a small sample size. The study was limited to patients with KRAS G12C mutated metastatic colorectal cancer. The study did not investigate other potential treatments.

    大腸癌 KRAS G12C 標靶來了:sotorasib、adagrasib 與 anti-EGFR 雙重打擊 · 2026 · DOI

  • Discovery of new anticancer molecular targets and identification of new therapeutic approaches are key strategies to improve the prognosis and treatment resistance of CRC patients, - Further studies on the exact mechanism and biological functions…

    UBC9 and PI3K Expression in Colorectal Cancer: Possible Prognostic Role · 2026 · DOI

Most-cited papers in Colorectal Cancer Treatments and Studies

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Open questions raised by papers listed on this page include: (1) The mechanisms underlying 5-FU resistance in CRC are not fully understood (“Targeting EHMT2 overcomes 5-fluorouracil resistance in colorectal cancer by…”, 2026); (2) There is limited evidence for the efficacy and safety of sorafenib therapy for advanced RCC in Japanese patients (“Unveiling VARS1: a key driver of colorectal cancer progression and immune…”, 2026); (3) There is a need to identify reliable predictors of chemotherapeutic efficacy in colon cancer (“Predictive Value of Serum Trace Elements for Chemotherapeutic Efficacy in…”, 2026); (4) There is a lack of real-world evidence on the efficacy of anti-EGFR agents in patients with RAS wild-type mCRC (“Real-world practices in RAS wild-type metastatic colorectal cancer patients…”, 2026); (5) There is a need for novel approaches for the prevention and treatment of colorectal cancer (“Enhanced antitumor efficacy of sulfasalazine and mesalazine in colorectal…”, 2026). 128 gap statements have been mined from Colorectal Cancer Treatments and Studies papers in our 4.5M-paper local library, which holds 750 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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