Therapy For Advanced Colorectal Cancer Research Articles

Broad Detection of Alterations Predicted to Confer Lack of Benefit From EGFR Antibodies or Sensitivity to Targeted Therapy in Advanced Colorectal Cancer.

A KRAS mutation represented the first genomic biomarker to predict lack of benefit from anti-epidermal growth factor receptor (EGFR) antibody therapy in advanced colorectal cancer (CRC). Expanded RAS testing has further refined the treatment approach, but understanding of genomic alterations underlying primary and acquired resistance is limited and further study is needed. We prospectively analyzed 4,422 clinical samples from patients with advanced CRC, using hybrid-capture based comprehensive genomic profiling (CGP) at the request of the individual treating physicians. Comparison with prior molecular testing results, when available, was performed to assess concordance. We identified a RAS/RAF pathway mutation or amplification in 62% of cases, including samples harboring KRAS mutations outside of the codon 12/13 hotspot region in 6.4% of cases. Among cases with KRAS non-codon 12/13 alterations for which prior test results were available, 79 of 90 (88%) were not identified by focused testing. Of 1,644 RAS/RAF wild-type cases analyzed by CGP, 31% harbored a genomic alteration (GA) associated with resistance to anti-EGFR therapy in advanced CRC including mutations in PIK3CA, PTEN, EGFR, and ERBB2. We also identified other targetable GA, including novel kinase fusions, receptor tyrosine kinase amplification, activating point mutations, as well as microsatellite instability. Extended genomic profiling reliably detects alterations associated with lack of benefit to anti-EGFR therapy in advanced CRC, while simultaneously identifying alterations potentially important in guiding treatment. The use of CGP during the course of clinical care allows for the refined selection of appropriate targeted therapies and clinical trials, increasing the chance of clinical benefit and avoiding therapeutic futility. Comprehensive genomic profiling (CGP) detects diverse genomic alterations associated with lack of benefit to anti-epidermal growth factor receptor therapy in advanced colorectal cancer (CRC), as well as targetable alterations in many other genes. This includes detection of a broad spectrum of activating KRAS alterations frequently missed by focused molecular hotspot testing, as well as other RAS/RAF pathway alterations, mutations shown to disrupt antibody binding, RTK activating point mutations, amplifications, and rearrangements, and activating alterations in downstream effectors including PI3K and MEK1. The use of CGP in clinical practice is critical to guide appropriate selection of targeted therapies for patients with advanced CRC.

Targeted therapy of advanced colorectal cancer

Targeted agents for advanced colorectal cancer mainly include inhibitors of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Studies show that bevacizumab and cetuximab can improve the prognosis of advanced colorectal cancer patients, but there is slight difference in the choice of chemotherapy regimens when combined with them. Bevacizumab and cetuximab can improve the overall survival of K-ras wild-type colorectal cancer patients similarly. The emergence of new targeted drugs such as aflibercept, regorafenib provides more choices for the targeted therapy of advanced colorectal cancer patients. Key words: Colorectal neoplasms; Molecular targeted therapy

Target hepatic artery regional chemotherapy and bevacizumab perfusion in liver metastatic colorectal cancer after failure of first-line or second-line systemic chemotherapy.

Colorectal cancer liver metastasis (CRLM) is a refractory disease after failure of first-line or second-line chemotherapy. Bevacizumab is recommended as first-line therapy for advanced colorectal cancer, but is unproven in CRLM through the hepatic artery. We report favorable outcomes with targeted vessel regional chemotherapy (TVRC) for liver metastatic gastric cancer. TVRC with FOLFOX and bevacizumab perfusion through the hepatic artery was attempted for CRLM for efficacy and safety evaluation. In a single-institution retrospective observational study, 246 patients with CRLM after at least first-line or second-line failure of systemic chemotherapy received TVRC with FOLFOX (i.e. oxaliplatin, leucovorin, and 5-fluorouracil). Of 246 patients, 63 were enrolled into two groups: group 1 (n=30) received bevacizumab and TVRC following tumor progression during previous TVRC treatments; group 2 (n=33) received TVRC plus bevacizumab for CRLM on initiating TVRC. There were no significant differences in the median survival time (14.7 vs. 13.2 months, P=0.367), although the median time to progression was significant (3.3 vs. 5.5 months, P=0.026) between groups. No severe adverse events related to TVRC plus bevacizumab perfusion occurred. Target vessel regional chemotherapy with FOLFOX plus bevacizumab perfusion through the hepatic artery was effective and safe in CRLM. The optimal combination of TVRC and bevacizumab needs further confirmation in future phase II-III clinical trials.

Targeting FGF receptors in colorectal cancer: from bench side to bed side.

Successful management of advanced colorectal cancer has been a challenging job for practicing oncologists as well as a priority for the oncology research community. The better understanding of the underlying patho-biology and critical pathway targets in this disease has contributed to major developments in that direction. In this review, we will revise the different biological and clinical aspects related to the use of FGFR pathway-targeted therapies in advanced colorectal cancer with particular focus on future perspectives in that regard.

UGT1A1 genotype and irinotecan therapy: general review and implementation in routine practice.

Irinotecan is a major drug in the treatment of advanced colorectal cancer. Its active form is the SN38 metabolite, which is cleared by the biliary route after glucuronidation by uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). UGT1A1 activity exhibits a wide intersubject variability, in part related to UGT1A1 gene polymorphisms. The present review on the impact of the deficient UGT1A1*28 variant on irinotecan efficacy and toxicity was produced by a French joint workgroup comprising the Group of Clinical Onco-pharmacology (GPCO-Unicancer) and the National Pharmacogenetics Network (RNPGx). It clearly emerges that for irinotecan doses at least equal to 180mg/m(2) , patients homozygous for the UGT1A1*28 allele are at increased risk of developing hematological and/or digestive toxicities. Irinotecan dose reduction is thus recommended in homozygous *28/*28 patients. In addition, this personalized medicine strategy aims to secure high-dose irinotecan administration (≥240mg/m(2) ) that have proven to be safe in homozygous *1/*1 patients only. The clinical relevance of this test is discussed in terms of treatment efficacy improvement, as increasing the irinotecan dose appears to be safe in patients not bearing a deficient allele. Best execution practices, cost-effectiveness, and result interpretation are discussed with the aim of facilitating the implementation of this analysis in clinical practice. The existence of networks of laboratories performing this test in routine hospital treatment, as in France, offers the prospect of widespread screening, thus guaranteeing equal access to safe treatment and optimized therapy for patients receiving irinotecan-based therapy in advanced colorectal cancer.

Growth pattern of colorectal liver metastasis as a marker of recurrence risk.

Despite improved therapy of advanced colorectal cancer, the median overall survival (OS) is still low. A surgical removal has significantly improved survival, if lesions are entirely removed. The purpose of this retrospective explorative study was to evaluate the prognostic value of histological growth patterns (GP) in chemonaive and patients receiving neo-adjuvant therapy. Two-hundred-fifty-four patients who underwent liver resection of colorectal liver metastases between 2007 and 2011 were included in the study. Clinicopathological data and information on neo-adjuvant treatment were retrieved from patient and pathology records. Histological GP were evaluated and related to recurrence free and OS. Kaplan-Meier curves, log-rank test and Cox regression analysis were used. The 5-year OS was 41.8% (95% CI 33.8-49.8%). Growth pattern evaluation of the largest liver metastasis was possible in 224 cases, with the following distribution: desmoplastic 63 patients (28.1%); pushing 77 patients (34.4%); replacement 28 patients (12.5%); mixed 56 patients (25.0%). The Kaplan-Meier analyses demonstrated that patients resected for liver metastases with desmoplastic growth pattern had a longer recurrence free survival (RFS) than patients resected for non-desmoplastic liver metastases (p=0.05). When patients were stratified according to neo-adjuvant treatment in the multivariate Cox regression model, hazard ratios for RFS compared to desmoplastic were: pushing (HR=1.37, 95% CI 0.93-2.02, p=0.116), replacement (HR=2.16, 95% CI 1.29-3.62, p=0.003) and mixed (HR=1.70, 95% CI 1.12-2.59, p=0.013). This was true for chemonaive patients as well as for patients who received neo-adjuvant treatment.

The nationwide genomic screening project for gastrointestinal cancer in Japan (GI-SCREEN): Simultaneous identification of KRAS, NRAS, BRAF, and PIK3CA mutation in advanced colorectal cancer (aCRC) (GI-SCREEN 2013-01).

578 Background: Recent studies confirmed that minor KRAS or NRAS mutations are associated with the resistance to anti-EGFR therapy for advanced colorectal cancer (aCRC). Although the impact of BRAF or PIK3CA mutation on efficacy of anti-EGFR therapy is still controversial, targeting agents for these mutations are under developing. Efficient screening systems for these relatively minor mutations with short turnaround time are necessary for the successful development of targeted therapies. Methods: This study was initiated in February 2014 as one of new nationwide genomic screening projects for advanced gastrointestinal cancer patients in Japan. Patients with aCRC who are planned to receive systemic chemotherapy were eligible. A total of 36 mutations of KRAS codon 61, 146, NRAS codon 12, 13, 61, BRAF codon 600, PIK3CA codon 542, 545, 546 and 1047 in genomic DNA of cancer cells were simultaneously analyzed at a quality-controlled central laboratory using Luminex (xMAP) technology in a single reaction using 50 ng of DNA. Results: As of August 31, 2014, this study is ongoing with the participation of 16 major cancer centers in Japan. A total of 437 aCRC patients were enrolled to this study and 361 tumor samples has been analyzed with success rate for genomic analysis of 100%. Among the 237 patients with KRAS exon 2 wild type, 28 patients (11.8%) had other RAS mutations and 15 patients (6.3%) had BRAF mutation. Twenty-seven of 437 patients had PIK3CA mutations (6.2%). One patient with BRAF mutation was enrolled in early clinical trials of BRAF inhibitors in combination with anti-EGFR antibody and most of other patients are still treated with standard chemotherapies, which may become future candidates for early clinical trials. Conclusions: From our preliminary results, this nationwide screening system enabled to detect rare mutations using limited amounts of samples from aCRC, which may facilitate the enrollment of patients in IND registration trials for targeted therapies as well as optimal individualized treatment.

Prognostic factors for survival with bevacizumab-based therapy in colorectal cancer patients: a systematic review and pooled analysis of 11,585 patients.

First-line chemotherapy+bevacizumab (BEV) is one of the standards of care in advanced colorectal cancer (CRC). Contrary to anti-EGFR agents, it is currently not possible to identify the ideal candidate for BEV-based chemotherapy due to the lack of predictors of outcomes. The aim of this study was to perform a systematic review of risk factors for survival after B-based chemotherapy for CRC. We performed a meta-analysis by searching on the databases PubMed, EMBASE, Web of Science and SCOPUS for a published series that focused on prognostic factors for BEV-based therapy in advanced CRC. Pooled hazard ratios (HR) were calculated by using a random-effects model for parameters that could be considered as potential prognostic factors in ≥3 papers. Twenty-nine studies, which included a total of 11,585 patients, were considered in this analysis. Five parameters were associated with survival in ≥3 papers: (1) a longer progression-free interval [PFS: HR 0.87, 95% confidence interval (CI) 0.78-0.97; P=0.01]; (2) a single site of metastases (HR 0.63, 95% CI 0.56-0.71; P<0.00001); (3) elevated lactate dehydrogenase (LDH: HR 2.08, 95% CI 1.69-2.57; P<0.00001); (4) KRAS mutation (HR 1.66, 95% CI 1.36-2.03; P<0.00001); and (5) poor performance status (PS: HR 1.99, 95% CI 1.41-2.82; P<0.0001). Clinical variables associated with prolonged survival, after first-line treatment with chemotherapy+BEV for metastatic CRC patients, included long PFS, low LDH levels, KRAS wild-type status, good PS and a single site of metastasis. They should be considered when stratifying patients for inclusion in randomized trials. Investigations into new prognostic factors based on tumor biology are needed and of high priority.

Role of First-Line Anti–Epidermal Growth Factor Receptor Therapy Compared With Anti–Vascular Endothelial Growth Factor Therapy in Advanced Colorectal Cancer: A Meta-Analysis of Randomized Clinical Trials

BackgroundMonoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy in combination with chemotherapy in the first-line therapy of advanced colorectal cancer (CRC). Data from randomized studies comparing these monoclonal antibodies as initial therapy is conflicting, and their comparative efficacy remains unclear. We aimed to evaluate the impact of these targeted therapies on patient outcomes by combining the data from randomized clinical trials. Materials and MethodsMEDLINE, PubMed, EMBASE, and meeting proceedings within the past 12 months were searched to identify relevant studies. All randomized phase II/III clinical trials of advanced CRC comparing an anti-EGFR therapy with an anti-VEGF agent in the first-line setting were included. Data were extracted on sample size, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). ResultsThree randomized studies comprising 2014 participants were included in the meta-analysis. For patients with KRAS wild type (KRAS-WT) CRC, the ORR was superior in patients who received first-line anti-EGFR therapy compared with those who received anti-VEGF therapy (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.09-1.58; P = .004). This effect was even stronger for all RAS-WT patients (OR, 1.46; 95% CI, 1.13-1.90; P = .004). There was no difference in PFS overall irrespective of the KRAS-WT (HR, 1.03; 95% CI, 0.93-1.13; P = .61) or all RAS-WT (HR, 0.92; 95% CI, 0.71-1.18; P = .50) status. The OS was significantly longer in the patients who received first-line anti-EGFR therapy compared with those who received anti-VEGF therapy (KRAS-WT: HR, 0.79; 95% CI, 0.65-0.97; P = .026; all RAS-WT: HR, 0.77; 95% CI, 0.63-0.95; P = .016). ConclusionThe results of our research show superior ORR and OS with first-line anti-EGFR therapy compared with anti-VEGF therapy in both KRAS-WT and all RAS-WT patients with advanced CRC. These results suggest that anti-EGFR monoclonal antibodies may be a real alternative to anti-VEGF therapy as initial treatment of advanced CRC.

Which strategy after first-line therapy in advanced colorectal cancer?

Second-line therapy for advanced colorectal cancer is an integral part of the treatment strategy that needs to be set from the beginning for each patient, bearing in mind the expected toxicities of chosen treatments, the patient's clinical condition, comorbidities, preferences, the aims of the treatment and the molecular status. Furthermore, the distinction between lines of therapy is no longer absolute. The perspective of "continuum of care" includes switching chemotherapy prior to disease progression, maintenance therapy, drug "holidays" if needed, surgical resection of metastases in selected patients, and seems to allow a tailored treatment, in which patients are more likely to benefit from exposure to all active agents, which is known to correlate with overall survival. The scenario of second-line treatment has changed dramatically over the years and could currently benefit from several options including chemotherapy with a single agent or in combination and the addition of molecular-targeted agents developed in the last decade, such as epidermal growth factor receptor antibodies (cetuximab, panitumumab) and vascular endothelial growth factor-targeting agents (bevacizumab, aflibercept), with the possibility of bevacizumab use even beyond first progression. The purpose of this review is to summarize the most important scientific data supporting the use of chemotherapy and the new biologic agents in the second-line setting in advanced colorectal cancer.

Intérêt du génotypage de l’UGT1A1 dans le cadre du traitement des cancers digestifs par irinotécan

Irinotecan is a cytotoxic agent administered by IV infusion in the treatment of advanced colorectal cancer. Its anticancer activity results from its bioactivation into SN-38 metabolite, which is cleared through glucuronidation by the hepatic enzyme uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). In the general population, there is wide inter-subject variability in UGT1A1 enzyme activity related to UGT1A1 gene polymorphisms. The French joint workgroup coming from the National Pharmacogenetic Network (RNPGx) and the Group of Clinical Oncologic Pharmacology (GPCO) herein presents an updated review dealing with efficacy and toxicity clinical studies related to UGT1A1 genetic variants. From a critical analysis of this review it clearly emerges that, for doses higher than 180mg/m2, hematologic and digestive irinotecan-induced toxicities could be prevented in daily clinical practice by generalizing the use of a simple pharmacogenetic test before starting treatment. The clinical relevance of this test is also discussed in terms of treatment efficacy improvement, with the possibility of increasing the irinotecan dose in patients not bearing the deleterious allele. This test involves using a blood sample to analyze the promoter region of the UGT1A1 gene (UGT1A1*28 allele). Best execution practices, laboratory costs, as well as results interpretation are described with the aim of facilitating the implementation of this analysis in clinical routine. The existence of a French laboratories network performing this test in clinical routine makes it possible to generalize UGT1A1 deficiency screening, so as to guarantee equal access to safe treatment and optimized irinorecan-based therapy for the many patients receiving irinotecan-based therapy in advanced colorectal cancer.

Biomarkers for immunotherapy: Results from the analysis of an HLA-status double-blind, biologically randomized phase II study of five therapeutic epitope-peptides with oxaliplatin-based chemotherapy as first-line therapy for advanced colorectal cancer (FXV study).

3038 Background: Biomarkers to predict the efficacy of immunotherapy have been awaited. A phase II study of five therapeutic epitope-peptides with oxaliplatin-based chemotherapy as first-line thera...

Mechanism underlying increased serum iron levels during FOLFOX/FOLFIRI therapy.

e14608 Background: We previously reported a significant transient increase in serum iron levels during FOLFOX and FOLFIRI therapies in advanced colorectal cancer (CRC) patients. Moreover, serum iro...

Combined epiregulin (EREG) and amphiregulin (AREG) expression levels as a biomarker of prognosis and panitumumab benefit in RAS-wt advanced colorectal cancer (aCRC).

3520 Background: RNA expression of epiregulin (EREG) ligands EREG and/or amphiregulin (AREG) has shown correlation with the efficacy of EGFR-targeted therapy in advanced colorectal cancer (aCRC). T...

Laparoscopic Surgery for Stage IV Colorectal Cancer

Laparoscopic surgery (Lap) is a feasible therapy in advanced colorectal cancer (CRC) without distant metastasis. Resection of primary lesion in stage IV CRC is now recognized as part of multimodal therapy. However, technical safety and invasiveness of Lap in stage IV CRC remain controversial. The feasibility of Lap in stage IV CRC was determined. Clinical outcomes were compared in primary colorectal resection using Lap, open surgery (Opn), and radical Lap for stages I to III CRC. No difference was observed regarding estimated blood loss and operative time between procedures. Postoperative recovery time and time to subsequent secondary therapy in the stage IV Lap group were significantly shorter than those in the Opn group. Similar results were observed for the 3-year overall survival rate. Lap for stage IV CRC is feasible and preferable in terms of technical safety and invasiveness. It may be useful in multimodal therapy for stage IV CRC.

The Challenge to Optimize Medical Therapy for Advanced Colorectal Cancer

The Challenge to Optimize Medical Therapy for Advanced Colorectal Cancer

Krabbamein í ristli og endaþarmi - yfirlitsgrein

Colorectal cancer is the third most common cancer in the Western hemisphere and the incidence increases with increasing age. Most colorectal cancers are localized with or without lymph node metastases. Up to 20% of patients present with metastatic disease, most commonly to the liver. Surgery is the only curative therapy for localized colorectal cancer and adjuvant chemotherapy is usually recommended for patients with lymph node metastases. Surgery, radiation therapy and chemotherapy are the key components of rectal cancer therapy. Selected patients with recurrent and metastatic disease can be salvaged with surgery but chemotherapy remains the mainstay of therapy for advanced colorectal cancer. Substantial progress has been observed in the treatment of metastatic colorectal cancer in recent years.

Effectiveness and safety of s-1-based therapy compared with 5-Fluorouracil-based therapy for advanced colorectal cancer: a meta-analysis.

Objectives. The aim of our study was to compare the efficacy and safety of S-1-based therapy (SBT) versus 5-fluorouracil-based therapy (FBT) for advanced colorectal cancer (ACRC). Methods. A meta-analysis of all eligible randomized controlled trials (RCTs) was performed using RevMan 5.1.0 software. Results. A total of 1625 patients from twelve RCTs including 820 patients in the SBT group and 805 patients in the FBT group were available for analysis. The meta-analysis of overall survival (hazards ratio HR = 0.94, 95% CI = 0.80–1.10), progression-free survival (HR = 1.03, 95% CI = 0.91–1.18), and overall response rate (odds ratio OR = 1.23, 95% CI = 1.00–1.53) showed no statistical significance between SBT group and FBT group. The statistically significant differences in the meta-analysis indicated less incidence of graded 3-4 neutropenia (OR = 0.49, 95% CI = 0.35–0.68) and nausea/vomit (OR = 0.41, 95% CI = 0.23–0.72) in the SBT group, and there was no statistically significant difference in the incidence of grade 3-4 anemia, thrombocytopenia, leucopenia, diarrhea, and treatment-related deaths between two groups. Conclusions. SBT had similar efficacy and better safety than FBT and was an attractive alternative to FBT for patients of ACRC, but further investigations in different populations would be needed to confirm it.

Novel cancer vaccines in combination with oxaliplatin-based chemotherapy as first-line therapy in advanced colorectal cancer: A randomized phase II study.

3006 Background: A phase I cancer vaccination trial using five novel HLA-A24-binding peptides derived from not only three oncoantigens, RNF43 (ring finger protein 43), TOMM34 (34 kDa translocase of the outer mitochondrial membrane), and KOC1 (IMP-3; IGF-II mRNA binding protein 3) but also antiangiogenic cancer vaccine targeting VEGFR1 (vascular endothelial growth factor receptor 1) and VEGFR2 had revealed safety and immunogenicity in advanced colorectal cancer (CRC) as presented at 2011 ASCO Oral Abstract Session (No. 2510). We further performed a phase II trial to evaluate the benefit of the cancer vaccination in combination with oxaliplatin-based chemotherapy as first-line therapy. Methods: Ninety-six chemotherapy naïve CRC pts were enrolled to evaluate primarily response rates (RR), and secondarily OS and PFS. Each of the five peptides (3 mg each) was mixed with 1.5 ml of IFA and subcutaneously administered weekly for 12 weeks and after then biweekly. Chemotherapy was performed simultaneously as mFOLFOX6 or XELOX with/without bevacizumab. All enrolled pts had received the therapy without knowing HLA-A status double-blindly, and the HLA genotype were key-opened at analysis point and then, the endpoints are evaluated between HLA-A*2402 positive and HLA-A*2402 negative group. Results: Between February 2009 and November 2012, a total of 96 pts were enrolled in this study. The cutoff date for the main analysis was January 31, 2013 (median duration of follow-up of 26.5months). mFOLFOX6 and XELOX were administered to 93 and 3 pts, respectively. Bevacizumab was used for 5 pts. RR, the primary study end point, was 61.5% (CR 1, PR 58, SD 33, PD 4). It seemed superior as compared to other reports. The median duration to reach the best responses (14 weeks; range 8-69) was surprisingly long and indicated the delayed effect of vaccination. PFS and OS were 8.2 m and 20.7 m, respectively. The HLA genotype will be key-opened at March 2013 and the endpoints will be presented between HLA-A*2402 positive and negative group at the meeting. Conclusions: The phase II cancer vaccine therapy demonstrated the promising response, and warrants further clinical studies. Clinical trial information: UMIN000001791.

Abstract 4914: ABCB5 expression in colorectal cancer circulating tumor cells correlates with metastatic disease progression.

Abstract Targeted personalized treatment approaches are critical for the development of successful therapies for advanced colorectal cancer (CRC). In this regard, circulating tumor cells (CTC) are of foremost interest as potential predictors of metastatic disease progression and patient therapeutic response. We have previously demonstrated that ATP-binding cassette member B5 (ABCB5) is expressed by cancer stem cells (CSC) in several human malignancies, including CRC, and that ABCB5 identifies therapy-refractory tumor subpopulations in CRC patients that correlate with disease progression. In order to evaluate the potential role of ABCB5 as a clinically relevant CTC marker, we utilized a human-to-mouse xenograft model system to examine the relationship of ABCB5-positive CRC-CTC to CRC metastasis. Human CRC tumor cells were grafted subcutaneously into immunocompromized NSG mice. 7 weeks after xenotransplantation, peripheral blood mononuclear cells and lungs were evaluated by qPCR for expression of human ABCB5 and GAPDH mRNAs. Expression analysis of these specimens revealed a significant positive correlation between peripheral blood human ABCB5 mRNA expression and aggregate metastatic disease load as determined by human GAPDH mRNA expression levels in lungs (r=0.8994, P=0.0147). Remarkably, no significant correlation existed between peripheral blood human GAPDH mRNA expression and metastatic disease load, indicating a unique and essential role of ABCB5-positive CSC-CTC in colorectal cancer metastatic disease progression. Significantly increased peripheral blood ABCB5 expression was also observed in a clinical series of UICC stages I-III colorectal cancer patients (n=105) compared to healthy controls (P&amp;lt;0.001). Thus, our results identify the CSC antigen ABCB5 as a novel molecular marker of metastasis-associated CRC-CTC and point to potential utility of ABCB5 as a prognostic indicator and predictor of therapeutic response in patients with advanced colorectal cancer. Citation Format: Qin Guo, Jie Ma, Brian J. Wilson, Martin Gasser, Ana Maria Waaga-Gasser, Markus H. Frank, Natasha Y. Frank. ABCB5 expression in colorectal cancer circulating tumor cells correlates with metastatic disease progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4914. doi:10.1158/1538-7445.AM2013-4914