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    BIOMARKER:

    APC mutation

    i
    Other names: APC, APC Regulator Of WNT Signaling Pathway, Protein Phosphatase 1, Regulatory Subunit 46, APC, WNT Signaling Pathway Regulator, Adenomatous Polyposis Coli Protein, Deleted In Polyposis 2.5, DP2.5, Adenomatosis Polyposis Coli Tumor Suppressor, Epididymis Secretory Sperm Binding Protein, Truncated Adenomatosis Polyposis Coli, Adenomatous Polyposis Coli (APC), WNT Signaling Pathway Regulator, Adenomatosis Polyposis Coli, Adenomatous Polyposis Coli, Protein APC, PPP1R46, BTPS2, DP2, DP3
    Entrez ID:
    324
    Related biomarkers:
    Mutation
    Others
    2d
    Effect of EPA-FFA on Polypectomy in Familial Adenomatous Polyposis (clinicaltrials.gov)
    P3, N=204, Active, not recruiting, S.L.A. Pharma AG | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jul 2024 | Trial primary completion date: Dec 2023 --> Jun 2024
    Enrollment closed • Trial completion date • Trial primary completion date
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    APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    10d
    Correlation between NGS panel-based mutation results and clinical information in colorectal cancer patients. (PubMed, Heliyon)
    Mutated genes were enriched in signaling pathways associated with CRC. The present findings have important implications for improving the personalized treatment of patients with CRC in China.
    Journal • Next-generation sequencing • MSi-H Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • APC (APC Regulator Of WNT Signaling Pathway)
    |
    TP53 mutation • KRAS mutation • MSI-H/dMMR • BRAF mutation • PIK3CA mutation • TP53 wild-type • APC mutation • SMAD4 mutation
    14d
    Management of Desmoid Disease in Familial Adenomatous Polyposis. (PubMed, Clin Colon Rectal Surg)
    Palliative surgical treatments are often considered in management of desmoid disease. Intestinal transplantation for severe desmoid disease is an emerging and promising option, though long-term data on efficacy and survival is limited.
    Review • Journal
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    APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    17d
    Altered lipid metabolism in APC-driven colorectal cancer: the potential for therapeutic intervention. (PubMed, Front Oncol)
    Furthermore, the downstream effects of this collaborative effort between aberrant Wnt/beta-catenin signaling and lipid metabolism are enhanced stemness, cellular proliferation, prooncogenic signaling, and survival. Understanding the mechanistic link between APC inactivation and alterations in lipid metabolism may foster identification of new therapeutic targets to enable development of more efficacious strategies for prevention and/or treatment of colorectal cancer.
    Review • Journal
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    APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    22d
    Telomere dysfunction alters intestinal stem cell dynamics to promote cancer. (PubMed, Dev Cell)
    Correspondingly, in this mouse model, GSK3β inhibition countered the actions of Wnt antagonists on intestinal stem cells, resulting in impaired adenoma formation of telomere dysfunctional Apc-mutant cells. Thus, telomere dysfunction contributes to cancer initiation through altered stem cell dynamics, identifying an interception strategy for human APC-mutant cancers with shortened telomeres.
    Journal
    |
    APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    1m
    The frequency of NRAS mutation in stool samples of Iranian colorectal cancers compared to Finnish patients. (PubMed, J Res Med Sci)
    Mutations in NRAS and FGFR3 were observed only in the Iranian cohort, while APC mutations were exclusive for the Finnish cohort. Genes involved in MAPK and PI3K-MAPK pathways showed a higher frequency of mutations in Iranian patients which may have therapeutic implications.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • STK11 (Serine/threonine kinase 11) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • APC (APC Regulator Of WNT Signaling Pathway) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • STK11 mutation • KIT mutation • APC mutation • AKT1 mutation
    1m
    Microenvironmental changes in familial adenomatous polyposis during colorectal cancer carcinogenesis. (PubMed, Cancer Lett)
    When compared with those in the sporadic CRC microenvironment, the composition and function of each cell type in the FAP-derived CRC microenvironment had differences. Our findings indicate that an immunosuppressive microenvironment is constructed from a precancerous stage in FAP.
    Journal
    |
    CD8 (cluster of differentiation 8)
    |
    APC mutation
    1m
    Colorectal cancer cells secreting DKK4 transform fibroblasts to promote tumour metastasis. (PubMed, Oncogene)
    Reduced β-catenin activity by a chemical inhibitor MSAB promoted the CRC metastasis. Our findings demonstrate why reduced β-catenin activity is needed for CRC progression and provide a mechanism by which interactions between CRC cells and stromal cells affect disease promotion.
    Journal
    |
    APC (APC Regulator Of WNT Signaling Pathway) • DKK4 (Dickkopf WNT Signaling Pathway Inhibitor 4)
    |
    APC mutation
    1m
    Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer. (PubMed, Cancer Cell)
    Furthermore, a machine learning approach attributing individual mutations to colibactin reveals that patients with colibactin-induced mutations are diagnosed at a younger age and that colibactin can induce a specific APC mutation. These approaches allow the sensitive detection of colibactin-induced mutations in ∼12% of CRC genomes and even in whole exome sequencing data, representing a crucial step toward pinpointing the mutagenic activity of distinct pks+E. coli strains.
    Journal
    |
    APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    1m
    Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis. (PubMed, Acta Pharm Sin B)
    In summary, we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin signaling. Chondroitin sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.
    Journal
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    APC (APC Regulator Of WNT Signaling Pathway) • TLE3 (TLE Family Member 3, Transcriptional Corepressor)
    |
    APC mutation
    2ms
    Differences in genomic, transcriptomic and immune landscape of prostate cancer (PCa) based on site of metastasis (mets) (AUA 2024)
    This study highlights distinct molecular profiles in metastatic prostate cancer (PCa) based on metastasis site, underlining the importance of personalized treatment strategies. The findings, particularly the variations in gene mutations and AR signaling, are crucial in tailoring management approaches for advanced PCa.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • BAP1 (BRCA1 Associated Protein 1) • IFNG (Interferon, gamma) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KMT2C (Lysine Methyltransferase 2C) • APC (APC Regulator Of WNT Signaling Pathway) • SPOP (Speckle Type BTB/POZ Protein)
    |
    TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • PTEN mutation • BAP1 mutation • APC mutation • AR mutation • AR splice variant 7
    |
    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    2ms
    Cancer-on-a-chip model shows that the adenomatous polyposis coli mutation impairs T cell engagement and killing of cancer spheroids. (PubMed, Proc Natl Acad Sci U S A)
    Realigning the CTL trajectories around localized killing cascades reveals that all CTLs transition to high engagement in the 2 h preceding the cascades, which confirms that the low engagement is the cause of reduced cytotoxicity. Beyond the study of APC mutations, this platform offers a robust way to compare cytotoxic cell efficiency of even closely related cell types, by relying on a multiscale cytometry approach to disentangle complex interactions and to identify the steps that limit the tumor destruction.
    Journal
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    APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    2ms
    Negative prognostic impact of Co-mutations in TGFβ and TP53 pathways in surgically resected rectal tumors following neoadjuvant chemoradiotherapy. (PubMed, Eur J Surg Oncol)
    Resected rectal tumor samples from patients without complete pathological response can be appropriately used to detect mutations. Co-mutations in the TGF-β and TP53 pathways may provide more prognostic information beyond commonly used clinical factors.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • APC (APC Regulator Of WNT Signaling Pathway) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    TP53 mutation • PIK3CA mutation • APC mutation
    2ms
    A Study of E7386 in Participants With Advanced Solid Tumor Including Colorectal Cancer (CRC) (clinicaltrials.gov)
    P1, N=70, Active, not recruiting, Eisai Co., Ltd. | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    RNF43 (Ring Finger Protein 43) • APC (APC Regulator Of WNT Signaling Pathway) • AXIN1 (Axin 1) • ZNRF3 (Zinc And Ring Finger 3)
    |
    APC mutation • CTNNB1 mutation • RNF43 mutation
    |
    E7386
    2ms
    Association between tumor genomic variants and the long term post surgical recurrence as detected by a tumor informed ctDNA assay (AACR 2024)
    These findings point to several genomic alterations that may underlie cancer recurrence after a long period of undetectable disease with a differential impact across different stages. This may allow, in the future, for a personalized surveillance strategy based on driver mutations and stage of the disease. Correlation of ctDNA positivity with clinical outcomes based on driver mutational status may inform to what extent tumor-specific characteristics drive patient outcomes following a successful surgery.
    Circulating tumor DNA
    |
    SMAD4 (SMAD family member 4) • APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation • SMAD4 mutation
    |
    Signatera™
    2ms
    Mucin phenotype and genetic alterations in non-V600E BRAF-mutated colorectal cancer. (PubMed, Hum Pathol)
    Considering the differences in mucin phenotype and genetic alterations, different modes of tumorigenesis are assumed for CRC with BRAF V600E mutation and non-V600E mutations. These findings are important in understanding the biology and treatment strategies for BRAF-mutant CRC.
    Journal
    |
    BRAF (B-raf proto-oncogene) • RNF43 (Ring Finger Protein 43) • APC (APC Regulator Of WNT Signaling Pathway) • MME (Membrane Metalloendopeptidase) • MUC2 (Mucin 2) • MUC5AC (Mucin 5AC) • MUC6 (Mucin 6)
    |
    BRAF V600E • APC mutation • RNF43 mutation • MUC5AC expression
    2ms
    Cepharanthine suppresses APC-mutant colorectal cancers by down-regulating the expression of β-catenin. (PubMed, Nat Prod Bioprospect)
    Moreover, CEP induced β-catenin transcription inhibition rather than the instability of β-catenin protein and mRNA contributes to reduction of β-catenin. Taken together, our findings identify CEP as the first β-catenin transcriptional inhibitor in the modulation of Wnt/β-catenin signaling and indicate CEP as a potential therapeutic option for the treatment of APC-mutated CRCs.
    Journal
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    CTNNB1 (Catenin (cadherin-associated protein), beta 1) • APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    2ms
    Aberrant β-Catenin Expression and Its Association With Epithelial-Mesenchymal Transition and Clinical Outcomes of Colorectal Cancer. (PubMed, Cureus)
    Conclusion This study underscores the importance of aberrant β-catenin expression in CRC progression, linked to APC mutations and EMT induction. Understanding these relationships could aid in developing targeted therapies for CRC.
    Clinical data • Journal
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    CTNNB1 (Catenin (cadherin-associated protein), beta 1) • APC (APC Regulator Of WNT Signaling Pathway) • CDH1 (Cadherin 1) • VIM (Vimentin) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
    |
    APC mutation • CDH1 expression • VIM expression • ZEB1 expression
    2ms
    A pair of primary colorectal cancer-derived and corresponding synchronous liver metastasis-derived organoid cell lines. (PubMed, Aging (Albany NY))
    IC50 assays confirmed that both cell lines were sensitive to 5-fluorouracil, oxaliplatin, SN-38, and sotorasib. The corresponding adherent cultured CWH22-2D/CLM22-2D cells were established and compared with commonly used CRC cell lines from the ATCC. Both organoids are publicly available to all researchers and will be useful tools for specific human CRC/CLM studies both in vitro and in vivo.
    Preclinical • Journal
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • SMAD4 (SMAD family member 4) • KMT2C (Lysine Methyltransferase 2C) • APC (APC Regulator Of WNT Signaling Pathway) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • CA 19-9 (Cancer antigen 19-9)
    |
    TP53 mutation • KRAS mutation • PIK3CA mutation • TP53 wild-type • APC mutation • SMAD4 mutation
    |
    5-fluorouracil • Lumakras (sotorasib) • oxaliplatin
    2ms
    Cribriform-morular Thyroid Carcinoma Arising in a Medulloblastoma Survivor: Two Metachronous Tumors Shared with the Activation of the Wnt Signaling Pathway. (PubMed, Int J Surg Pathol)
    She had no history of FAP and harbored an unexpected somatic mutation of the APC gene in the CMTC tumor. The potential agents involved in the pathogenesis of the two molecular-linked tumors other than FAP were discussed in this report.
    Journal
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    CTNNB1 (Catenin (cadherin-associated protein), beta 1) • APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    2ms
    Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer. (PubMed, Int J Cancer)
    By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • SMAD4 (SMAD family member 4) • CEACAM5 (CEA Cell Adhesion Molecule 5) • APC (APC Regulator Of WNT Signaling Pathway) • SYNE1 (Spectrin Repeat Containing Nuclear Envelope Protein 1)
    |
    KRAS mutation • BRAF mutation • APC mutation • SYNE1 mutation
    2ms
    Fibromatosis of the Breast: Clinicopathologic Features and Treatment Outcomes (USCAP 2024)
    β-catenin nuclear immunoreactivity is not a consistent feature in fibromatosis of the breast. Given that these lesions are managed via active surveillance, we in turn have relied less on β-catenin expression and more on morphologic assessment and, if needed, NGS to render the diagnosis of fibromatosis.
    Clinical
    |
    APC mutation • CTNNB1 mutation
    |
    Oncomine Focus Assay
    2ms
    Next-Generation Sequencing Experience of Colorectal Cancer at a Quebec Health Care Centre (USCAP 2024)
    Our study is concordant with larger CRC sequencing studies. Although, the main targetable mutations are covered by the Focus Panel, a considerable proportion of specimens had no identifiable mutations. As more treatments become available, more extensive panels are necessary.
    Next-generation sequencing
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
    |
    KRAS mutation • BRAF mutation • PIK3CA mutation • HER-2 mutation • APC mutation • PMS2 mutation
    |
    Illumina Focus Panel
    2ms
    Molecular and immunohistochemical study of APC exon 16 and its possible role in colorectal carcinoma development. (PubMed, Heliyon)
    Similarly, although not statistically significant, the percentage of APC positive staining increased with poorer tumor differentiation, rather than declining. Therefore, the APC exon 16 mutation and expression analysis provides insights into colorectal cancer progression, with the rs459552 mutation correlating with grade and may promoting aggression.
    Journal
    |
    APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    3ms
    β-catenin mediates growth defects induced by centrosome loss in a subset of APC mutant colorectal cancer independently of p53. (PubMed, PLoS One)
    Consistent with this notion, β-catenin inhibition using XAV939 or ICG-001 partially prevented centrinone-induced death and rescued the growth two APC-mutant organoid lines tested. Our study reveals a novel role for canonical WNT signaling in regulating centrosome loss-induced growth defect/death in a subset of APC-mutant colorectal cancer independently of the classical p53 pathway.
    Journal
    |
    CTNNB1 (Catenin (cadherin-associated protein), beta 1) • APC (APC Regulator Of WNT Signaling Pathway) • PLK4 (Polo Like Kinase 4)
    |
    TP53 mutation • APC mutation
    |
    foscenvivint (PRI724) • XAV-939
    3ms
    A Study of REC-4881 in Participants With Cancers Which Have an AXIN1 or APC Mutation (clinicaltrials.gov)
    P2, N=60, Recruiting, Recursion Pharmaceuticals Inc. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    APC (APC Regulator Of WNT Signaling Pathway) • RAS (Rat Sarcoma Virus) • AXIN1 (Axin 1)
    |
    APC mutation
    |
    REC-4881
    3ms
    Genetic specificity study using next-generation sequencing (NGS) of peritoneal metastatic colorectal cancer compared to primary colorectal cancer. (PubMed, Genes Genomics)
    The small number of surgical cases of peritoneal metastases was a limitation of our sample size. Nevertheless, we identified differences in the alterations of specific genes between primary and peritoneal metastases. Acquiring additional cases and collecting more data will provide deeper insights into these cancers.
    Journal • Next-generation sequencing • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • APC (APC Regulator Of WNT Signaling Pathway)
    |
    TP53 mutation • KRAS mutation • PIK3CA mutation • APC mutation
    3ms
    APC mutations disrupt β-catenin destruction complex condensates organized by Axin phase separation. (PubMed, Cell Mol Life Sci)
    Surprisingly, truncated APC did not affect the formation of condensates, and GSK 3β and CK1α were unsuccessfully recruited, preventing β-catenin phosphorylation and resulting in accumulation in the cytoplasm of CRCs. Besides, we propose that the phase separation ability of Axin participates in the nucleus translocation of β-catenin and be incorporated and concentrated into transcriptional condensates, affecting the transcriptional activity of Wnt signaling pathway.
    Journal
    |
    CTNNB1 (Catenin (cadherin-associated protein), beta 1) • APC (APC Regulator Of WNT Signaling Pathway) • AXIN1 (Axin 1)
    |
    APC mutation
    3ms
    Tissue-Predisposition to Cancer Driver Mutations. (PubMed, Cells)
    The frequency of cancer driver mutations among tissues is non-uniform: for instance, mutations in APC are particularly frequent in colorectal cancer, and 99% of chronic myeloid leukemia patients harbor the driver BCR-ABL1 fusion mutation, which is rarely found in solid tumors. Here, we provide a mechanistic framework that aims to explain how tissue-specific features, ranging from epigenetic underpinnings to the expression of viral transposable elements, establish a molecular basis for selecting cancer driver mutations in a tissue-specific manner.
    Review • Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    BCR-ABL1 fusion • APC mutation • BCR-ABL1 mutation
    3ms
    CYP26A1 Links WNT and Retinoic Acid Signaling: A Target to Differentiate ALDH+ Stem Cells in APC-Mutant CRC. (PubMed, Cancers (Basel))
    Notably, in wt-APC-CRCs, decreased CYP26A1 improved patient survival. These findings have strong potential for clinical translation.
    Journal
    |
    APC (APC Regulator Of WNT Signaling Pathway) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • CYP26A1 (Cytochrome P450 Family 26 Subfamily A Member 1)
    |
    APC mutation
    3ms
    A Study of REC-4881 in Participants With Cancers Which Have an AXIN1 or APC Mutation (clinicaltrials.gov)
    P2, N=60, Not yet recruiting, Recursion Pharmaceuticals Inc. | Initiation date: Oct 2023 --> Jan 2024
    Trial initiation date • Metastases
    |
    APC (APC Regulator Of WNT Signaling Pathway) • RAS (Rat Sarcoma Virus) • AXIN1 (Axin 1)
    |
    APC mutation
    |
    REC-4881
    3ms
    TUPELO: Evaluate REC-4881 in Patients With FAP (clinicaltrials.gov)
    P1/2, N=73, Recruiting, Recursion Pharmaceuticals Inc. | Phase classification: P2 --> P1/2 | N=37 --> 73
    Phase classification • Enrollment change
    |
    APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    |
    REC-4881
    3ms
    A novel molecular subtyping based on multi-omics analysis for prognosis predicting in colorectal melanoma: A 16-year prospective multicentric study. (PubMed, Cancer Lett)
    A machine learning algorithm named Support Vector Machine (SVM) was applied to predict the classification of CRM patients based on protein expression in the external testing cohort. Two subtypes of primary CRM with clinical and proteomic characteristics provides a reference for subsequent diagnosis and treatments.
    Journal
    |
    APC (APC Regulator Of WNT Signaling Pathway)
    |
    APC mutation
    3ms
    BET protein-dependent E2F pathway activity confers bell-shaped type resistance to tankyrase inhibitors in APC-mutated colorectal cancer. (PubMed, Cancer Lett)
    Combination of tankyrase and BET inhibitors significantly suppress tumor growth in a mouse xenograft model. These observations suggest that the combination of tankyrase and BET inhibitors may be a useful therapeutic approach to overcome the resistance of a subset of CRCs to tankyrase inhibitors.
    Journal
    |
    APC (APC Regulator Of WNT Signaling Pathway) • BRD3 (Bromodomain Containing 3)
    |
    KRAS mutation • APC mutation
    4ms
    NELF and PAF1C complexes are core transcriptional machineries controlling colon cancer stemness. (PubMed, Oncogene)
    Additionally, the chemical inhibition of CDK12 (a downstream transcription CDK of PAF1C) suppressed colon cancer stemness. These results suggest that NELF and PAF1C are the core transcriptional machineries that control expression of colon cancer stemness-inducing genes and may be therapeutic targets for colon cancer.
    Journal
    |
    CDK12 (Cyclin dependent kinase 12) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CDK9 (Cyclin Dependent Kinase 9) • CDC73 (Cell Division Cycle 73)
    |
    APC mutation
    4ms
    A Phase 1/2a Study of IMM-1-104 in Participants With Previously Treated, RAS-Mutant, Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=210, Recruiting, Immuneering Corporation | N=156 --> 210
    Enrollment change • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • HRAS (Harvey rat sarcoma viral oncogene homolog) • APC (APC Regulator Of WNT Signaling Pathway)
    |
    KRAS mutation • NRAS mutation • KRAS wild-type • RAS mutation • HRAS mutation • APC mutation
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium • IMM-1-104
    4ms
    Correlation of the Pro-Inflammatory Cytokines IL-1β, IL-6, and TNF-α, Inflammatory Markers, and Tumor Markers with the Diagnosis and Prognosis of Colorectal Cancer. (PubMed, Life (Basel))
    We also showed that the acute inflammatory markers of erythrocyte sedimentation rate, C-reactive protein, and fibrinogen, and the tumor markers of CEA and CA 19.9 can be useful in diagnosis and prognosis in patients with CRC. Considering the association between pro-inflammatory cytokines and CRC, the development of new targeted therapies against IL-1β, IL-6, and TNF-α can improve patient care and the CRC survival rate.
    Journal
    |
    IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CEACAM5 (CEA Cell Adhesion Molecule 5) • APC (APC Regulator Of WNT Signaling Pathway) • IL1B (Interleukin 1, beta) • CRP (C-reactive protein)
    |
    APC mutation
    4ms
    Differences in genomic, transcriptomic, and immune landscape of prostate cancer (PCa) based on site of metastasis (mets). (ASCO-GU 2024)
    We elucidate molecular and immunologic mechanisms of metastatic tropism in advanced PCa. These data may facilitate future drug development.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • BAP1 (BRCA1 Associated Protein 1) • IFNG (Interferon, gamma) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KMT2C (Lysine Methyltransferase 2C) • APC (APC Regulator Of WNT Signaling Pathway) • SPOP (Speckle Type BTB/POZ Protein)
    |
    TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • PTEN mutation • BAP1 mutation • APC mutation • AR splice variant 7
    |
    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    5ms
    Improved Drug-Response Prediction Model of APC Mutant Colon Cancer Patient-Derived Organoids for Precision Medicine. (PubMed, Cancers (Basel))
    However, there is no established correlation between oxaliplatin and drug-response prediction...However, clusterin induced apoptosis inhibition and cell survival, demonstrating a significant correlation with drug resistance. This study's findings are expected to contribute to increasing the accuracy of drug-response prediction in patient-derived APC mutant colorectal cancer organoids, thereby providing reliable precision medicine and improving patient survival rates.
    Journal
    |
    APC (APC Regulator Of WNT Signaling Pathway) • BIRC5 (Baculoviral IAP repeat containing 5) • CLU (Clusterin)
    |
    APC mutation • BIRC5 expression
    |
    5-fluorouracil • oxaliplatin • leucovorin calcium
    5ms
    Relationship Between Immunophenotypes, Genetic Profiles, and Clinicopathologic Characteristics in Small Bowel Adenocarcinoma. (PubMed, Am J Surg Pathol)
    The SBA immunophenotype correlated with tumor location, biological behavior, and genomic alterations. Our results suggest that the molecular pathway involved in carcinogenesis of gastric-type SBA differs from that of intestinal-type SBA.
    Journal
    |
    MUC1 (Mucin 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MME (Membrane Metalloendopeptidase) • MUC4 (Mucin 4, Cell Surface Associated) • CDX2 (Caudal Type Homeobox 2) • MUC2 (Mucin 2) • MUC5AC (Mucin 5AC) • MUC6 (Mucin 6)
    |
    APC mutation • CTNNB1 mutation • MUC1 expression • MUC4 expression • MUC5AC expression
    5ms
    High-resolution transcriptional signature to predict survival benefit in colorectal cancer (CRC) treated with EGFR inhibitors (EGFRi) independent of RAS/BRAF mutation status or tumor sidedness. (ASCO-GI 2024)
    Sponsored by NCI, NCI Background: Cetuximab (CTX) and Panitumumab (PMB) therapies directed at EGFR have been restricted to left-sided CRC harboring wild-type KRAS (KRASWT), limiting their utility. Our data suggest that CTX-S may predict longer survival on EGFRi, surprisingly independent of RAS/BRAF mutation status as well as tumor sidedness. Patients with high CTX-S had increased prevalence of CMS2 and harbored more APC and TP53 mutations. A strong EGFRi biomarker would likely expand the utility of EGFRi to right-sided tumors and possibly to RASMUT tumors.
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • APC (APC Regulator Of WNT Signaling Pathway) • RAS (Rat Sarcoma Virus)
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    TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • KRAS wild-type • BRAF wild-type • RAS mutation • RAS wild-type • APC mutation • RAS wild-type + BRAF wild-type • RNF43 mutation
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    MI Tumor Seek™
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    Erbitux (cetuximab) • Vectibix (panitumumab)
    5ms
    Comparison of colorectal cancer (CRC) characteristics across genetic ancestries: Implications for early cancer detection (ECD). (ASCO-GI 2024)
    These data confirm previous results in AFR populations, and reveal novel differences in the EAS and LAT populations. Findings from this study may provide information for developing risk stratification and prevention strategies for the early detection of cancer and provide rationale for precision treatment based on ancestry. >*p<0.05, **p<0.001
    Tumor mutational burden
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability)
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    TP53 mutation • KRAS mutation • BRAF mutation • PIK3CA mutation • APC mutation
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    Signatera™