Targeted Treatment against Cancer Stem Cells in Colorectal Cancer.

The cancer stem cell (SC) theory proposes that a population of SCs serves as the driving force behind fundamental tumor processes, including metastasis, recurrence, and resistance to therapy. The standard of care for patients with stage III and high-risk stage II colorectal cancer (CRC) includes surgery and adjuvant chemotherapy. Fluoropyrimidines and their combination with oxaliplatin increased the cure rates, being able to eradicate the occult metastatic SC in a fraction of patients.

Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study.

Purpose: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies.

Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study.

Background: Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT.

Methods: This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment.

Evolution of Mutations in Cell-Free DNA of Patients with Tissue Wild-Type Metastatic Colorectal Cancer Receiving First-Line Treatment: The PERSEIDA Study.

The serial analysis of cell-free DNA (cfDNA) enables minimally invasive monitoring of tumor evolution, providing continuous genetic information. PERSEIDA was an observational, prospective study assessing the cfDNA (/) mutational status evolution in first-line, metastatic CRC, wild-type (according to baseline tumor tissue biopsy) patients. Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression.

Effect of aflibercept plus FOLFIRI and potential efficacy biomarkers in patients with metastatic colorectal cancer: the POLAF trial.

Background: Aflibercept is an antiangiogenic drug against metastatic colorectal cancer (mCRC) combined with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI); however, no antiangiogenic biomarker has yet been validated. We assessed aflibercept plus FOLFIRI, investigating the biomarker role of baseline vascular endothelial growth factor A (VEGF-A) and angiotensin-converting enzyme (ACE).

Methods: Phase II trial in oxaliplatin-treated mCRC patients who received aflibercept plus FOLFIRI.

Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD).

Introduction: Retrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy.

Patients And Methods: Survival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling.

Relationships Between Köhne Category/Baseline Tumor Load and Early Tumor Shrinkage, Depth of Response, and Outcomes in Metastatic Colorectal Cancer.

Background: In metastatic colorectal cancer (mCRC), there are limited data on associations between early tumor shrinkage (ETS), depth of response (DpR), and patient characteristics.

Methods: Data from patients with RAS wild-type mCRC who had participated in the PRIME (NCT00364013) and PEAK (NCT00819780) studies were analyzed retrospectively. ETS and DpR were assessed by baseline Köhne category/BRAF status (PRIME) and baseline tumor load (pooled PRIME and PEAK).

First-Line Biological Agents Plus Chemotherapy in Older Patients with Metastatic Colorectal Cancer: A Retrospective Pooled Analysis.

Background: Biologicals, in combination with chemotherapy, are recommended as first-line treatment of metastatic colorectal cancer (mCRC); however, evidence guiding the appropriate management of older patients with mCRC is limited.

Objective: This study was undertaken to compare the efficacy and safety outcomes in older versus younger patients with mCRC who received first-line biological therapy.

Methods: This retrospective analysis used pooled data from five trials undertaken by the Spanish Cooperative Group for the Treatment of Digestive Tumours.

Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: the BIBABRAX study.

Purpose: To evaluate the health-related quality of life (HRQoL), global health status (GHS), and deterioration-free survival of an elderly population (> 70 years) with unresectable locally advanced (LAPC) or metastatic pancreatic cancer (mPC) treated with nab-paclitaxel in combination with gemcitabine.

Methods: In this open-label, single-arm, multicenter, phase II trial, patients received 4-week cycles of intravenous (i.v.

First-line panitumumab plus capecitabine for the treatment of older patients with wild-type RAS metastatic colorectal cancer. The phase II, PANEL study.

Background: Despite the high morbidity and mortality of metastatic colorectal cancer (mCRC) in older patients, they have been underrepresented in clinical trials and their optimal treatment is yet to be determined. This open-label phase II study evaluated the benefits of panitumumab and capecitabine as a first-line chemotherapy regimen in older patients with wild-type [WT] RAS mCRC.

Patients And Methods: Patients (≥70 years; ECOG≤2) received 3-week cycles of panitumumab (9 mg/kg on day 1) plus capecitabine (850 mg/m twice daily on days 1-14) until disease progression or unacceptable toxicity.

A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients.

Background: Targeted agents are standard treatment for RAS wild-type metastatic colorectal cancer in the first- and second-line settings. This phase 2 study determined the benefit of targeting the epidermal growth factor receptor (EGFR) with panitumumab plus irinotecan in irinotecan-refractory patients.

Methods: KRAS exon-2 wild-type patients failing prior irinotecan received panitumumab (6 mg/kg) and irinotecan (180 mg/m²) every 2 weeks.

Anti-proliferative and Anti-invasive Effect of Polysaccharide-rich Extracts from in Colon Cancer Cells.

Colorectal cancer (CRC) is one of leading causes of mortality in western countries and novel treatment strategies are required. The medicinal application of mushrooms has been used in traditional medicine in many oriental countries. Polysaccharide-rich extracts obtained from certain medicinal mushroom species have shown antitumor effects in different experimental models.

A Randomized Phase II Study of Axitinib as Maintenance Therapy After First-line Treatment for Metastatic Colorectal Cancer.

Introduction: The aim of this study was to evaluate the efficacy and safety of maintenance therapy with axitinib versus placebo following induction therapy in patients with metastatic colorectal cancer (mCRC).

Patients And Methods: In this double-blinded, phase II trial, patients with mCRC who had not progressed after 6 to 8 months of first-line chemotherapy were randomized to receive axitinib (5 mg twice a day) (arm A) or placebo (arm B).

Results: Forty-nine patients were included: 25 in arm A and 24 in arm B.

Exploratory pooled analysis evaluating the effect of sequence of biological therapies on overall survival in patients with wild-type metastatic colorectal carcinoma.

Background: The aim of this study was to evaluate the optimal sequence of targeted therapies (epidermal growth factor receptor inhibitors (EGFRi) and vascular endothelial growth factor inhibitors (VEGFi)), combined with chemotherapy, in patients with wild-type (WT) metastatic colorectal carcinoma (mCRC). Exploratory analyses of overall survival (OS) for patients treated with either first-line panitumumab (EGFRi) and second-line VEGFi therapy, or first-line bevacizumab (VEGFi) and second-line EGFRi, were conducted.

Methods: Patients from PEAK (NCT00819780), PRIME (NCT00364013) and Study 181 (NCT00339183), with WT or WT/ WT tumours, were included in the analyses.

Hakai overexpression effectively induces tumour progression and metastasis in vivo.

At early stages of carcinoma progression, epithelial cells undergo a program named epithelial-to-mesenchymal transition characterized by the loss of the major component of the adherens junctions, E-cadherin, which in consequence causes the disruption of cell-cell contacts. Hakai is an E3 ubiquitin-ligase that binds to E-cadherin in a phosphorylated-dependent manner and induces its degradation; thus modulating cell adhesions. Here, we show that Hakai expression is gradually increased in adenoma and in different TNM stages (I-IV) from colon adenocarcinomas compared to human colon healthy tissues.

Author Correction: Exploratory analyses assessing the impact of early tumour shrinkage and depth of response on survival outcomes in patients with RAS wild-type metastatic colorectal cancer receiving treatment in three randomised panitumumab trials.

The authors would like to include the following changes in the published article.

Exploratory analyses assessing the impact of early tumour shrinkage and depth of response on survival outcomes in patients with RAS wild-type metastatic colorectal cancer receiving treatment in three randomised panitumumab trials.

Purpose: To report exploratory analyses of early tumour shrinkage (ETS) and depth of response (DpR) in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), receiving the first-line treatment in three randomised panitumumab trials.

Methods: Data from the PRIME (NCT00364013), PEAK (NCT00819780) and PLANET (NCT00885885) studies were included. Median DpR, the proportion of patients achieving ETS ≥ 20% or ≥ 30% at week 8, and the impact of ETS and DpR (including by category) on outcome were analysed.

Proteomic Analysis of the E3 Ubiquitin-Ligase Hakai Highlights a Role in Plasticity of the Cytoskeleton Dynamics and in the Proteasome System.

Carcinoma, the most common type of cancer, arises from epithelial cells. The transition from adenoma to carcinoma is associated with the loss of E-cadherin and, in consequence, the disruption of cell-cell contacts. E-cadherin is a tumor suppressor, and it is down-regulated during epithelial-to-mesenchymal transition (EMT); indeed, its loss is a predictor of poor prognosis.

Prognostic and predictive markers of response to treatment in patients with locally advanced unresectable and metastatic pancreatic adenocarcinoma treated with gemcitabine/nab-paclitaxel: Results of a retrospective analysis.

Background: Recent studies support the use of gemcitabine and nab-paclitaxel in adults with locally advanced unresectable or metastatic pancreatic adenocarcinoma although insufficient data are available on prognostic and predictive markers of response to treatment.

Objective: The objective of this study is to identify treatment response markers in patients with locally advanced unresectable or metastatic pancreatic adenocarcinoma.

Materials And Methods: This is an observational, retrospective, and multicenter study.

First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD).

Background: In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations.

Methods: Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI.

Current controversies in the management of metastatic colorectal cancer.

The factors affecting the decisions for the treatment for patients with metastatic colorectal cancer (mCRC) are related to the patient, the tumor, and the treatment itself. Both cetuximab and panitumumab are anti-EGFR monoclonal antibody options for patients with RAS wild-type tumors. Several trials comparing these agents with bevacizumab are analyzed in this paper.

Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach.

Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity.

Circulating miR-200c and miR-141 and outcomes in patients with breast cancer.

Background: The deregulation of microRNAs in both tumours and blood has led to the search for microRNAs to indicate the presence of cancer and predict prognosis. We hypothesize the deregulation of miR-200c/miR-141 in the whole blood can identify breast cancer (BC), and could be developed into a prognostic signature.

Methods: The expression of miR-200c and miR-141 were examined in bloods (57 stage I-IV BC patients and 20 age-matched controls) by quantitative reverse-transcription PCR.