Cancer Family
Malignant Digestive System Neoplasm
CI-CAN-00000229Explore in graph →
Loading cancer entity…
Cancer Family
CI-CAN-00000229Explore in graph →
Variants & evidence
1,218 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| SMAD4 Underexpression1 | ||||||||
| (prognostic) | Malignant Pancreatic Neoplasm | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID6445Using univariate analysis, the results showed that underexpression of SMAD4 had a strong relationship with poor OS in pancreatic cancer patients. More specifically, the underexpression of SMAD4 was re… (full text at CIViC) PMID 26947875 · Shugang et al., 2016 · Open in CIViC | civic |
| SPRY2 UNDEREXPRESSION1 | ||||||||
| (prognostic) | Gastric Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID6455The correlation between FGFR2/SPRY2 and clinicopathologic factors was analyzed by Chi-square to screen the FGFR2/SPRY2-relevant factors. SPRY2 low expression was demonstrated to be significantly assoc… (full text at CIViC) PMID 28002800 · Xu et al., 2017 · Open in CIViC | civic |
| STK11 D194E1 | ||||||||
| Everolimus | Malignant Pancreatic Neoplasm | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID1617Case study of a 46-year old male patient with Peutz-Jeghers Syndrome and pancreatic cancer. A germline STK11 D194E mutation was identified with LOH in the tumor sample. phospho-S6 ribosomal protein st… (full text at CIViC) PMID 21189378 · Klümpen et al., 2011 · Open in CIViC | civic |
| STK11 Loss1 | ||||||||
| Roflumilast | Pancreatic Ductal Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID12555In a preclinical study using STK11/LKB1-deficient pancreatic ductal adenocarcinoma (PDAC) cell lines (TB 32047, PANC-1, SUIT2, SU86.86, KPC792) and C57BL/6 orthotopic mouse models (n = 5 per group), t… (full text at CIViC) PMID 38461159 · Zhang et al., 2024 · Open in CIViC | civic |
| ALK Fusion1 | ||||||||
| Ceritinib | Colon Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID5952Patients with metastatic colorectal cancer with STRN-ALK fusion, sporadic microsatellite instability high (MSI-H) and KRAS R164Q received ALK inhibitor ceritinib. After pts received ceritinib perinumb… (full text at CIViC) PMID 26933125 · Yakirevich et al., 2016 · Open in CIViC | civic |
| THBS2 UNDEREXPRESSION1 | ||||||||
| (prognostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID974172 patients treated with neoadjuvant concurrent chemoradiotherapy (CCRT) were retrospectively analyzed for expression of thrombospondin 2 (THBS2) using IHC (discovery set with 46 rectal cancer patien… (full text at CIViC) PMID 26807188 · Lin et al., 2015 · Open in CIViC | civic |
| High5 | ||||||||
| (prognostic) | Rectal AdenocarcinomaALIAS | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID13211This study evaluated genomic biomarkers associated with treatment response and clinical outcomes in patients with locally advanced rectal adenocarcinoma (LARC) treated with neoadjuvant chemoradiation … (full text at CIViC) PMID 37260182 · Lee et al., 2023 · Open in CIViC | civic |
| 〃 | Colon Adenocarcinoma | Prognostic | B | Supports Better Outcome | 3 | accepted | EID13242In a single-center observational study of 102 patients with microsatellite stable (MSS) metastatic colon cancer receiving standard treatments, high tumor mutational burden (TMB ≥10 mutations/Mb) was a… (full text at CIViC) PMID 39639373 · Di Mauro et al., 2024 · Open in CIViC | civic |
| (diagnostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Diagnostic | ||||||
| TNC TNC-L2 | ||||||||
| (prognostic) | Malignant Pancreatic Neoplasm | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID9604In a clinical study including 106 patients, over expression of TNC-L is significantly associated with decreased OS by a multivariate analysis (p = 0.0005). PMID 31463696 · Hagiwara et al., 2020 · Open in CIViC | civic |
| Gemcitabine | Malignant Pancreatic Neoplasm | Predictive | D | Supports Resistance | 4 | submitted | EID9603In an in vitro study, an increased gemcitabine IC50 significantly correlated with increased concentration of TNfnA-D (TNC-L). Resistance reached a platform at 20 ug/ml (p < 0.01). PMID 20686216 · Gong et al., 2010 · Open in CIViC | civic |
| TOP1 Amplification2 | ||||||||
| Cetuximab + FOLFIRI RegimenCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12143The OncoBird framework utilizes data from the open-label, randomized phase III FIRE-3 trial, which involved patients with metastatic colorectal carcinoma who received either cetuximab or bevacizumab i… (full text at CIViC) PMID 37666855 · Ohnmacht et al., 2023 · Open in CIViC | civic |
| Irinotecan | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 1 | accepted | EID888FFPE tumor samples from 78 patients with colorectal cancer, who had received irinotecan monotherapy were analyzed with a FISH dual-probe. TOP1 gain was nonsignificantly associated with objective respo… (full text at CIViC) PMID 24256029 · Nygård et al., 2014 · Open in CIViC | civic |
| TOP1 EXPRESSION1 | ||||||||
| Irinotecan | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID912498 patients were retrospectively analyzed for topoisomerase 1 expression (IHC). In the subgroup of patients treated with irinotecan (38% of the 498), those patients expressing Topoisomerase I had a b… (full text at CIViC) PMID 19775480 · Kostopoulos et al., 2009 · Open in CIViC | civic |
| TP53 L3 Domain Mutation1 | ||||||||
| (prognostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID3041A prospective study was performed using tumor and normal tissue from 160 colorectal cancer patients undergoing resection. 68 of 160 patients showed tumor p53 mutation, and 18 of 68 cases showed mutati… (full text at CIViC) PMID 12433709 · Russo et al., 2002 · Open in CIViC | civic |
| TP53 Mutation4 | ||||||||
| (prognostic) | Esophageal Squamous Cell CarcinomaALIAS | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID519In a retrospective study of patients with esophageal carcinoma, those with mutations in TP53 had worse overall survival. PMID 19941080 · Yamasaki et al., 2010 · Open in CIViC | civic |
| Chemotherapy | Gastric Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID850In this meta-analysis of 13 studies (564 patients) p53 positivity as defined by high protein expression and/or p53 mutation was associated with improved response to chemotherapy (risk ratio [RR] = 0.7… (full text at CIViC) PMID 24740294 · Xu et al., 2014 · Open in CIViC | civic |
| Cisplatin + Doxorubicin + EtoposideCombination | Gastric CarcinomaALIAS | |||||||
| TP53 Overexpression1 | ||||||||
| Cisplatin + Etoposide + MitomycinCombination | Malignant Gastric Neoplasm | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID2799In a Phase II trial of 25 patients with metastaic gastric cancer, patients received preoperative high dose chemotherapy (HDCT) consisting of etoposide, cisplatin and mitomycin. Patients with greater t… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC | civic |
| TP53 R175H1 | ||||||||
| EAP Protocol | Gastric CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | — | accepted | EID2310In a study of 25 patients with advanced gastric cancer, mutations in TP53 were identified in 32% of primary tumors. TP53 mutations were associated with an improved response to preoperative treatment o… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC | civic |
| TP53 R213P1 | ||||||||
| EAP Protocol | Gastric CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | — | accepted | EID2819In a study of 25 patients with advanced gastric cancer, mutations in TP53 were identified in 32% of primary tumors. TP53 mutations were associated with an improved response to preoperative treatment o… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC | civic |
| TP53 R273C1 | ||||||||
| Cisplatin + Etoposide + MitomycinCombination | Gastric CarcinomaALIAS | Predictive | C | Does Not Support Sensitivity Response | 3 | accepted | EID2292A female patient taking part in a 25 patient gastric cancer trial was diagnosed at age 46, and received preoperative high dose chemotherapy (HDCT). Japanese Society for Gastric Cancer Response Score w… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC | civic |
| TP53 G245S + TP53 R213* + TP53 R273C1 | ||||||||
| Pazopanib + VorinostatCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID12732In the phase I study of pazopanib and vorinostat in 36 patients with advanced solid tumors, detection of hotspot TP53 mutation was associated with a higher rate of SD ≥6 months/PR, longer median PFS (… (full text at CIViC) PMID 25669829 · Fu et al., 2015 · Open in CIViC | civic |
| TP53 R282L1 | ||||||||
| EAP Protocol | Gastric CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | — | accepted | EID2818In a study of 25 patients with advanced gastric cancer, mutations in TP53 were identified in 32% of primary tumors. TP53 mutations were associated with an improved response to preoperative treatment o… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC | civic |
| TP53 V143A1 | ||||||||
| (diagnostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Diagnostic | C | Supports N/A | 2 | submitted | EID2890TP53 mutations were identified in 38/80 colorectal cancer subjects at a Taiwanese hospital. One patient harbored the V143A mutation, and the authors note this is the first identification of V143A in c… (full text at CIViC) PMID 12795343 · Chang et al., 2003 · Open in CIViC | civic |
| TP53 V197E1 | ||||||||
| (predisposing) | Esophageal Squamous Cell CarcinomaALIAS | Predisposing | C | Supports Predisposition | 1 | submitted | EID9846Analysis of 77 esophageal squamous cell carcinoma tumor and normal samples for germline mutations revealed a rare TP53 V197E variant in a single patient. The V197E mutation is in the DNA-binding domai… (full text at CIViC) PMID 30833958 · Deng et al., 2019 · Open in CIViC | civic |
| TP53 Wildtype2 | ||||||||
| Capecitabine + Cetuximab + OxaliplatinCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID875In this retrospective biomarker analysis of the EXPERT-C trial, patients with TP53 wild-type status had a statistically significant better progression free survival (PFS) (89.3% vs 65.0% at 5 years; h… (full text at CIViC) PMID 24957073 · Sclafani et al., 2014 · Open in CIViC | civic |
| Chemotherapy | Esophageal Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID906Patients with p53 wild type (as defined by low expression and/or wild-type tp53 gene) had a higher response rate to chemotherapy-based treatment (total major response [MR]: risk ratio [RR] = 1.09, 95 … (full text at CIViC) PMID 23515910 · Zhang et al., 2013 · Open in CIViC | civic |
| TP53 Y220C1 | ||||||||
| Cisplatin + Etoposide + MitomycinCombination | Gastric CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID2306A male patient taking part in a 25 patient gastric cancer trial was diagnosed at age 50, harbored a TP53 mutation and received preoperative high dose chemotherapy (HDCT). Japanese Society for Gastric … (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC | civic |
| NTRK1 Fusion1 | ||||||||
| Larotrectinib + LestaurtinibSubstitutes | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID978NTRK1 fusions (one LMNA-NTRK1 and two TPM3-NTRK1) were identified in 2% of Korean colorectal cancer patients (147 patients). TrkA (NTRK1) protein expression was associated with presence of NTRK1 gene … (full text at CIViC) PMID 26716414 · Park et al., 2016 · Open in CIViC | civic |
| NTRK1 Fusion1 | ||||||||
| Larotrectinib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID11706A female patient, 43 presented with right lower quadrant pain, and was surgically treated for perforated appendicitis including segmental small-bowel resection. Invasive adenocarcinoma stage IIB (pT4a… (full text at CIViC) PMID 35815302 · Kasi et al., 2022 · Open in CIViC | civic |
| TYMS 3TRP/3TRP genotype1 | ||||||||
| Fluorouracil + IrinotecanCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID678The TYMS 5' 3TPR germline variant was significantly correlated with lower response to irinotecan plus 5-fluorouracil treatment in colorectal cancer patients. 149 metastatic CRC patients treated with i… (full text at CIViC) PMID 20628391 · Martinez-Balibrea et al., 2010 · Open in CIViC | civic |
| TYMS Amplification2 | ||||||||
| 5-Fluorouracil/Salicylic Acid Topical Solution | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID12097Genomic DNA from liver metastases of four different colorectal cancer patients who had previously undergone 5-FU-based adjuvant chemotherapy was evaluated using digital karyotyping. TYMS amplification… (full text at CIViC) PMID 14970324 · Wang et al., 2004 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID12098The TYMS DNA copy number was analyzed in 111 patient samples, divided into two groups: those exposed to 5-FU (n = 62) and those not exposed to 5-FU (n = 49). It was found that the 5-FU exposed group h… (full text at CIViC) PMID 20727737 · Watson et al., 2010 · Open in CIViC | civic |
| TYMS Decreased RNA expression1 | ||||||||
| Fluorouracil | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID13313Reduced TYMS expression by shRNA increased fluorouracil cytotoxicity in HCT-116, HT-29, and SW620 colorectal cancer cells, with approximately 3- to 8-fold enhancement of drug sensitivity. PMID 21449674 · Muhale et al., 2011 · Open in CIViC | civic |
| TYMS Overexpression1 | ||||||||
| Raltitrexed | Gastric Adenocarcinoma | Predictive | B | Supports Resistance | 2 | accepted | EID929In 125 gastric tumors, plasma and tissue mRNA levels of TYMS were lower in the raltitrexed sensitive group compared to the resistant group (p = 0.007 and 0.013, respectively). PMID 22422354 · Shen et al., 2012 · Open in CIViC | civic |
| UCK2 Decreased RNA expression1 | ||||||||
| Fluorouracil | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID13316shRNA-mediated reduction of UCK2 expression significantly sensitized HCT-116, HT-29, and SW620 colorectal cancer cells to fluorouracil, decreasing IC50 approximately 3- to 6-fold. PMID 21449674 · Muhale et al., 2011 · Open in CIViC | civic |
| UGT1A Overexpression1 | ||||||||
| Ganetespib | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID866Colorectal cancer cell lines were evaluated for response to the HSP90 inhibitor ganetespib. Correlating cell line-specific IC50s with the corresponding gene expression patterns revealed a possible re… (full text at CIViC) PMID 25210794 · Landmann et al., 2014 · Open in CIViC | civic |
| UMPS Decreased RNA expression1 | ||||||||
| Fluorouracil | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID13322shRNA-mediated reduction of UMPS expression increased resistance to fluorouracil by approximately twofold in HCT-116 and SW620 colorectal cancer cells, as measured by increased IC50. PMID 21449674 · Muhale et al., 2011 · Open in CIViC | civic |
| UNG Decreased RNA expression1 | ||||||||
| Fluorouracil | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID13319Reduction of UNG expression by shRNA significantly sensitized all three colorectal cancer cell lines to fluorouracil. Across the UNG, NME1, and RRM1 experiments, IC50 decreases ranged from approximate… (full text at CIViC) PMID 21449674 · Muhale et al., 2011 · Open in CIViC | civic |
| ALK Fusion1 | ||||||||
| Crizotinib | Colorectal Adenocarcinoma | Predictive | E | Supports Sensitivity Response | 1 | accepted | EID133426 colorectal adenocarcinoma samples were run on Affymetrix human Exon 1.0 arrays and a computational method that assessed differential 5' and 3' gene expression for each gene was used to find potenti… (full text at CIViC) PMID 19737969 · Lin et al., 2009 · Open in CIViC | civic |
| VEGFA Decreased Peri-therapeutic Expression1 | ||||||||
| Bevacizumab + Fluorouracil + Irinotecan + LevoleucovorinCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID818Decreased peri- and post-therapeutic expression of VEGFA were significantly associated with response to FOLFIRI plus bevacizumab in 57 patients with metastatic CRC. PMID 25973082 · Tsai et al., 2015 · Open in CIViC | civic |
| VEGFA low ratio of VEGF165b/VEGFtotal2 | ||||||||
| Bevacizumab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 5 | rejected | EID9296Tumor samples from the phase III trial of FOLFOX4 bevacizumab were assessed for VEGF165b and VEGFtotal by immunohistochemistry and scored relative to normal mucosal tissue. Low ratio of VEGF165b/VEG… (full text at CIViC) PMID 23104894 · Bates et al., 2012 · Open in CIViC | civic |
| 〃 | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID9358Tumor samples with low ratio of VEGF165b/VEGFtotal treated with bevacizumab compared to placebo showed a trend toward improved PFS (HR 0.49; 95% CI, 0.26 to 0.93). The trend was not significant with p… (full text at CIViC) PMID 23104894 · Bates et al., 2012 · Open in CIViC | civic |
| VEGFA Overexpression1 | ||||||||
| Bevacizumab | Malignant Gastric Neoplasm | Predictive | B | Supports Sensitivity Response | 2 | submitted | EID7216Patients with high baseline plasma VEGF-A levels showed a trend toward improved overall survival (hazard ratio [HR], 0.72; 95% CI, 0.57 to 0.93) versus patients with low VEGF-A levels (HR, 1.01; 95% C… (full text at CIViC) PMID 22565005 · Van Cutsem et al., 2012 · Open in CIViC | civic |
| VEGFA Overexpression of VEGF121 and VEGF1101 | ||||||||
| Bevacizumab | Malignant Gastric Neoplasm | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID9298In a clinical trials of 774 patients, patients with high plasma VEGF121 and VEGF110 levels treated with bevacizumab compared to placebo showed a trend toward improved OS (HR 0.72; 95% CI, 0.57 to 0.93… (full text at CIViC) PMID 22565005 · Van Cutsem et al., 2012 · Open in CIViC | civic |
| VEGFA VEGF165b Overexpression1 | ||||||||
| Bevacizumab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | D | Supports Reduced Sensitivity | 4 | submitted | EID9289Nude mice were injected with VEGF165b-transfected LS174t colon cancer cells or control LS174t cells and treated with bevacizumab. VEGF165b expressing tumors grew faster than those not expressing VEGF1… (full text at CIViC) PMID 18349829 · Varey et al., 2008 · Open in CIViC | civic |
Data updated 16 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Does Not Support Negative |
| 2 |
| submitted |
EID12971Whole genome sequencing and staining of anti-CD3 and anti-CD8 antibodies were performed on fresh-frozen tissue from 6 Lynch syndrome associated microsatellite (MSI) colorectal cancer patients and 20 M… (full text at CIViC) PMID 41535448 · Martin et al., 2026 · Open in CIViC |
| civic |
| Durvalumab + TremelimumabCombination | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12042In this randomized phase II trial, 180 patients with microsatellite stable (MSS) colorectal cancer were treated with either a combination of durvalumab and tremelimumab (D+T; n=119) or best supportive… (full text at CIViC) PMID 38727700 · Loree et al., 2024 · Open in CIViC | civic |
| Pembrolizumab | Malignant Colorectal NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 1 | accepted | EID12574Microsatellite instability-high (MSI-H) colorectal cancers (CRC) respond to immune checkpoint inhibitors (ICPIs), but response rates vary, often < 50%, highlighting the need for better stratification.… (full text at CIViC) PMID 31038663 · Schrock et al., 2019 · Open in CIViC | civic |
| Predictive |
| C |
| Supports Sensitivity Response |
| 1 |
| accepted |
EID2820In a study of 25 patients with advanced gastric cancer, mutations in TP53 were identified in 32% of primary tumors. TP53 mutations were associated with an improved response to preoperative treatment o… (full text at CIViC) PMID 14514923 · Bataille et al., 2003 · Open in CIViC |
| civic |
| Gemcitabine | Malignant Pancreatic Neoplasm | Predictive | B | Supports Sensitivity Response | 2 | submitted | EID8282In this retrospective analysis, tumor samples from 101 patients from the CONKO-001 trial, who received curatively intended surgery for pancreatic adenocarcinoma (PDAC) followed by adjuvant chemotherap… (full text at CIViC) PMID 32234756 · Sinn et al., 2020 · Open in CIViC | civic |