*  Phase II Study of Panitumumab with Fluorouracil in Patients With KRAS Wild-type Metastatic Colorectal Cancer(PF Study) -...
This trial is investigating the efficacy and tolerability of panitumumab + fluorouracil in patients with metastatic KRAS wild-type colorectal cancer.
  http://adisinsight.springer.com/trials/700213020
*  KRAS Wild-type Metastatic Colorectal Cancer Trial - Full Text View - ClinicalTrials.gov
Vectibix® (panitumumab) is a FDA approved drug (BLA-125147) indicated as a single agent for the treatment of EGFR-expressing metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy regimens. Approval is based on progression-free survival; no data demonstrate an improvement in disease-related symptoms or increased survival.. DRUG DESCRIPTION Vectibix® (panitumumab) is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). Panitumumab has an approximate molecular weight of 147 kDa. Panitumumab is produced in genetically engineered mammalian (Chinese Hamster Ovary) cells.. Panitumumab will be given on this study at 6 mg/kg, IV over 1 hr ...
  https://clinicaltrials.gov/show/NCT00879385
*  Study of AUY922 and Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer - Full Text View - ClinicalTrials.gov
Any continuous-dosing (i.e. daily dosing, every-other-day dosing, Monday-Wednesday-Friday dosing, weekly etc.) of systemic anti-cancer treatment for which the recover period is not known, or investigational drugs (i.e. targeted agents) within a duration of ≤ 5 half lives of the agent and their active metabolites (if any ...
  https://clinicaltrials.gov/ct2/show/NCT01294826?recr=Open&cond=%22Rectal+Diseases%22&rank=11
*  Plus it
Purpose: Although cetuximab, an anti-EGF receptor (EGFR) monoclonal antibody, is an effective treatment for patients with KRAS wild-type metastatic colorectal cancer (mCRC), its clinical use is limited by onset of resistance.. Experimental Design: We characterized two colorectal cancer models to study the mechanisms of acquired resistance to cetuximab.. Results: Following chronic treatment of nude mice bearing cetuximab-sensitive human GEO colon xenografts, cetuximab-resistant GEO (GEO-CR) cells were obtained. In GEO-CR cells, proliferation and survival signals were constitutively active despite EGFR inhibition by cetuximab treatment. Whole gene expression profiling identified a series of genes involved in the hepatocyte growth factor (HGF)-MET-dependent pathways, which were upregulated in GEO-CR cells. Furthermore, activated, phosphorylated MET was detected in GEO-CR cells. ...
  http://clincancerres.aacrjournals.org/content/early/2013/11/13/1078-0432.CCR-13-0423
*  ASPECCT: A Study of Panitumumab Efficacy and Safety Compared to Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal...
The EQ-5D is a standardized instrument for use as a generic measure of health outcome. The health state index measures the following 5 health dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension contains 3 levels of response to reflect degree of problems participants have experienced: no problem (1), some problem (2) and extreme problems (3). The health states for each respondent are converted into a single index number using a specified set of weights. Resulting scores can range from 1.0 and -0.594. A higher score indicates a more preferred health status with 1.0 representing perfect health and 0 representing death. Negative scores are possible and represent health states regarded as less preferable than death (0). Repeated measures mixed model includes treatment, geographic region, ECOG score, assessment week, and treatment by assessment week interaction as fixed effects, and participants a random effect ...
  https://clinicaltrials.gov/show/NCT01001377
*  Plus it
Somatic genetic mutation in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene has been linked to poor prognosis and resistance to various targeted therapeutics in Non Small Cell Lung Cancer (NSCLC). Therapeutic strategies that target tumors harboring these mutations represent an unmet medical need. In this study, we investigated the relationship between antifolate sensitivity and KRAS mutation/amplification status in NSCLC.. Human NSCLC cell lines (KRAS wild type, KRAS mutant non-amplified and KRAS mutant amplified) were treated with Methotrexate (MTX) or Pemetrexed (PEM) and assayed for proliferation after 72h. In these studies, 5 out of 7 ...
  http://mct.aacrjournals.org/content/10/11_Supplement/PR-2
*  Randomized Phase II Study of AZD6244 (Mitogen-activated Protein Kinase Inhibitor) MEK-Inhibitor With Erlotinib in KRAS Wild...
Background:. AZD6244 (ARRY-142886) is an investigational anticancer drug that is designed to block a critical component (MEK (methyl ethyl ketone)) of a pathway (MAP (mitogen-activated protein) kinase pathway) that causes some lung cancer cells to grow. The MAP kinase pathway could be overactive in a proportion of lung cancers, including some which also have another mutation in a protein known as KRAS (Kirsten rat sarcoma viral oncogene homolog). Approximately 20% of lung cancers have KRAS mutations which can make some cancer treatments including erlotinib, a standard anticancer treatment drug less effective. Researchers are interested in determining whether AZD6244 is effective in treating advanced NSCLC (non small cell lung cancer), including KRAS mutated lung cancer that has not responded to standard therapy.. ...
  https://clinicaltrials.gov/ct2/show/NCT01229150?term=AZD6244%2FErlotinib%3A+NSCLC&rank=1
*  Randomized Phase II Study of AZD6244 (Mitogen-activated Protein Kinase Inhibitor) MEK-Inhibitor With Erlotinib in KRAS Wild...
Background:. AZD6244 (ARRY-142886) is an investigational anticancer drug that is designed to block a critical component (MEK (methyl ethyl ketone)) of a pathway (MAP (mitogen-activated protein) kinase pathway) that causes some lung cancer cells to grow. The MAP kinase pathway could be overactive in a proportion of lung cancers, including some which also have another mutation in a protein known as KRAS (Kirsten rat sarcoma viral oncogene homolog). Approximately 20% of lung cancers have KRAS mutations which can make some cancer treatments including erlotinib, a standard anticancer treatment drug less effective. Researchers are interested in determining whether AZD6244 is effective in treating advanced NSCLC (non small cell lung cancer), including KRAS mutated lung cancer that has not responded to standard therapy.. ...
  https://clinicaltrials.gov/ct2/show/record/NCT01229150
*  Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Acute Myeloid Leukemia - Full Text View - ClinicalTrials.gov
Positive for RAS mutation (neuroblastoma RAS viral [v-ras] oncogene homolog [NRAS] codon 12, 13, 61 mutation or Kirsten rat sarcoma viral oncogene homolog [KRAS] codon 12, 13, 61 mutation) at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory prior to study entry; mutational testing will be performed on bone marrow sample and/or peripheral blood; patients with previously known RAS mutations prior to study entry may be considered positive for RAS mutation for eligibility prior to a CLIA-certified laboratory confirmation of such a mutation at the discretion of the investigator; (appropriate blood and/or bone marrow samples must be taken ...
  https://clinicaltrials.gov/ct2/show/NCT01907815?term=acute+myelomonocytic+leukemia&recr=Open&rank=20
*  A Trial of Maintenance ADAPT Therapy With Capecitabine and Celecoxib in Patients With Metastatic Colorectal Cancer - Full Text...
PRIMARY OBJECTIVES:. I. To determine the rate of complete response 2 years following the initiation of first line 5-FU (fluorouracil) based chemotherapy in patients with initially unresected metastatic colorectal cancer who are then treated on the activating cancer stem cells (CSCs) from dormancy and priming them for subsequent targeting (ADAPT) protocol.. SECONDARY OBJECTIVES:. I. To determine overall survival, relapse free survival (if complete response [CR]) based on intent to treat (ITT) analysis.. II. To determine quality of life while on ADAPT therapy.. III. To determine the effects of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) mutation status, resection and radiation on response to ADAPT therapy.. OUTLINE:. Patients proceed to surgery, radiation therapy with ADAPT therapy followed by maintenance ADAPT therapy, or ADAPT therapy. Eligible patients undergo surgical ...
  https://clinicaltrials.gov/ct2/show/study/NCT01729923?view=results
*  A Trial of Maintenance ADAPT Therapy With Capecitabine and Celecoxib in Patients With Metastatic Colorectal Cancer - Full Text...
PRIMARY OBJECTIVES:. I. To determine the rate of complete response 2 years following the initiation of first line 5-FU (fluorouracil) based chemotherapy in patients with initially unresected metastatic colorectal cancer who are then treated on the activating cancer stem cells (CSCs) from dormancy and priming them for subsequent targeting (ADAPT) protocol.. SECONDARY OBJECTIVES:. I. To determine overall survival, relapse free survival (if complete response [CR]) based on intent to treat (ITT) analysis.. II. To determine quality of life while on ADAPT therapy.. III. To determine the effects of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) mutation status, resection and radiation on response to ADAPT therapy.. OUTLINE:. Patients proceed to surgery, radiation therapy with ADAPT therapy followed by maintenance ADAPT therapy, or ADAPT therapy. Eligible patients undergo surgical ...
  https://clinicaltrials.gov/show/NCT01729923
*  BAY 43-9006 Plus Cetuximab to Treat Colorectal Cancer - Tabular View - ClinicalTrials.gov
Background:. Colorectal cancer (CRC) is a major public health problem; 5-year survival with widespread metastatic disease is less than 5%. Expression of epidermal growth factor receptor (EGFR) or up-regulation of the gene occurs in 60-80% of cases. Therapies targeting EGFR, like cetuximab, have shown activity in the treatment of solid tumors like CRC.. Cetuximab is Food and Drug Administration (FDA) approved for the treatment of EGFR-expressing CRC, but clinical responses to cetuximab are seen in only 10% of EGFR-expressing CRC. Recent data strongly implicate KRAS (Kirsten rat sarcoma viral oncogene homolog) mutations as a mechanism of resistance to anti-EGFR antibody therapies such as cetuximab.. Another major pathway implicated in colon carcinogenesis is the vascular endothelial growth factor (VEGF) pathway, which is involved in angiogenesis and is a validated target for therapy in CRC. BAY 43-9006 is both a Raf kinase ...
  https://clinicaltrials.gov/ct2/show/record/NCT00326495
*  S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent...
PRIMARY OBJECTIVES:. I. To compare overall survival (OS) in the entire study population. II. To compare progression-free survival (PFS) by institutional review of epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH)-positive patients.. SECONDARY OBJECTIVES:. I. To compare OS and PFS by centralized review in EGFR FISH-positive patients. II. To compare PFS by centralized image review and by institutional review in the entire study population.. III. To compare the response rate (confirmed plus unconfirmed, complete and partial responses) in a subset of patients with measurable disease in EGFR FISH-positive patient and the entire study population.. IV. To assess the toxicities of these treatment regimens. V. To prospectively test EGFR FISH as a predictive marker for the selection of patients for cetuximab plus chemotherapy.. III. To evaluate the role of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ...
  https://clinicaltrials.gov/ct2/show/record/NCT00946712
*  OriGene - KRAS (NM 004985) Human ORF cDNA Clone
KRAS - KRAS mutant (Q61R), Myc-DDK-tagged ORF clone of Homo sapiens v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), transcript variant b as transfection-ready DNA available for purchase from OriGene - Your Gene Company.
  http://www.origene.com/orf_clone/Search/retrieve_results.mspx?sku=RC400114
*  Ras subfamily - Wikipedia
Ras is a family of related proteins which is expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells (cellular signal transduction). Ras is the prototypical member of the Ras superfamily of proteins, which are all related in 3D structure and regulate diverse cell behaviours. When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation and survival. Mutations in ras ...
  https://en.wikipedia.org/wiki/Ras_subfamily
*  Gene expression profiling of laterally spreading tumors | BMC Gastroenterology | Full Text
The morphological features of tumors are closely related to their growth patterns [8]. Polypoid tumors are believed to exhibit a predominantly vertical growth pattern, rather than a horizontal growth pattern, while non-polypoid tumors are believed to exhibit the opposite pattern, resulting in horizontal growth. Although there are some reports that LSTs have distinct biological characteristics compared to polypoid tumors [9, 10], the mechanism by which the LST conformation is generated remains unknown.. LSTs are believed to have distinct characteristics in terms of histological and genetic features [11]. Several molecular characteristics of LSTs have been described, including alteration of the adenomatous polyposis coli (APC) gene or β-catenin [12-14] affecting the WNT/APC/β-catenin signaling pathway, mutation of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) [12, 15-20]. However, the molecular ...
  https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-015-0295-1
*  Biomarker - Panitumumab Response With KRAS Wild Type MCC - Full Text View - ClinicalTrials.gov
Colon cancer affects 20,000 Canadians a year. Despite efforts to improve screening, 8,500 patients will die of the disease (1). The agents used in both the adjuvant and metastatic setting have dramatically changed over the past ten years. Even with the optimal treatment and careful follow-up many patients will develop metastasis. For most this is an incurable condition and the median survival for these patients is only 2 years (2).. Therapy with 5-Fluorouracil (FU)/Leucovorin, oxaliplatin and irinotecan with or without bevacizumab are conventionally used as first and second line therapy for metastatic colorectal cancer. Third line therapy options are limited to anti-epidermal growth factor receptor (EGFR) therapy Cetuximab or Panitumumab either as monotherapy or in combination with Irinotecan. Recent data (see Table 1) has demonstrated that KRAS mutation status is a predictor of benefit to anti-EGFR therapy, with wild-type tumours demonstrating a response ...
  https://clinicaltrials.gov/ct2/show/NCT00853931
*  Efficacy and Safety Study of Imprime PGG With Cetuximab in Subjects With Stage IV KRAS-Mutated Colorectal Cancer - Full Text...
Study BT-CL-PGG-CRC0821 is a Phase 2, open-label, multicenter, efficacy and safety study. It will be conducted using a two-stage design with the intention of determining the initial efficacy of Imprime PGG in combination with a monoclonal antibody (MAb; cetuximab) in the treatment of KRAS-mutant colorectal cancer (CRC). Both stages will be conducted in subjects with Stage IV CRC demonstrating the KRAS gene mutation. All subjects will receive Imprime PGG at 4 mg/kg and standard doses of cetuximab; Imprime PGG and cetuximab will be administered in 6-week cycles. Subjects will dose until progression of disease or discontinuation from the study for other reasons; e.g., safety, non-compliance. The initial cetuximab dose will be 400 mg/m2 on Cycle 1/Day1 and subsequent doses of cetuximab will be 250 mg/m2 weekly. Imprime PGG will be dosed weekly at 4 mg/kg. Tumor measurements and determination of tumor responses ...
  https://clinicaltrials.gov/ct2/show/NCT00912327
*  Efficacy and Safety Study of Imprime PGG With Cetuximab in Subjects With Stage IV KRAS-Mutated Colorectal Cancer - Tabular View...
Study BT-CL-PGG-CRC0821 is a Phase 2, open-label, multicenter, efficacy and safety study. It will be conducted using a two-stage design with the intention of determining the initial efficacy of Imprime PGG in combination with a monoclonal antibody (MAb; cetuximab) in the treatment of KRAS-mutant colorectal cancer (CRC). Both stages will be conducted in subjects with Stage IV CRC demonstrating the KRAS gene mutation. All subjects will receive Imprime PGG at 4 mg/kg and standard doses of cetuximab; Imprime PGG and cetuximab will be administered in 6-week cycles. Subjects will dose until progression of disease or discontinuation from the study for other reasons; e.g., safety, non-compliance. The initial cetuximab dose will be 400 mg/m2 on Cycle 1/Day1 and subsequent doses of cetuximab will be 250 mg/m2 weekly. Imprime PGG will be dosed weekly at 4 mg/kg. Tumor measurements and determination of tumor responses ...
  https://clinicaltrials.gov/ct2/show/record/NCT00912327
*  Plus it
RAS mutations are found in one-third of all human cancers. Among the three RAS isoforms - HRAS, KRAS and NRAS, KRAS is the most commonly mutated gene (in 86% of RAS-driven cancers) and the mutations are often detected in pancreatic, colorectal and lung cancers. RAS proteins function as molecular switches by alternating between inactive GDP-bound and active GTP-bound states. The active or inactive state of RAS proteins is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In the GTP-bound state, ...
  http://cancerres.aacrjournals.org/content/77/13_Supplement/1366
*  SMART: Secondary literature for RAS domain
Ras proteins are members of a superfamily of small GTPases that are involved in many aspects of cell growth control. The ras p21 protooncogene products, H-ras, K-ras, and N-ras, transmit signals from growth factor receptors to a cascade of protein kinases that begins with the Raf protooncogene product, and leads to alterations in transcription factors and cell cycle proteins in the nucleus. This cascade is controlled at several points: Ras p21 proteins are regulated by GAPs and by exchange factors, whose activities are altered by growth factor receptor activation (Boguski and McCormick, 1993: Nature 366:643-654). Transmission of signals from ...
  http://smart.embl.de/smart/show_secondary.cgi?domain=RAS
*  KRAS2 - v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog) - aka: Ki-ras, ...
Standard faecal occult blood testing for colorectal cancer has the benefit of being non-invasive, however, there are problems with sensitivity (tumours may bleed intermittently or not at all) and specificity. Since DNA is continuously released into the faecal stream there is potential for developing new screening tests to detect mutations in tumour DNA. KRAS mutations in tumours can be detected in stools some patients with colorectal cancer. Detection of KRAS mutations alone may be limited as theses occur in less than half of all colorectal cancers and may occur in pancreatic hyperplasia and other non-malignant conditions. However, research into developing tests for multiple DNA alterations, including KRAS, may offer great potential for new non-invasive screening for colorectal cancer with high levels of sensitivity and specificity ...
  http://www.cancerindex.org/geneweb/KRAS2.htm
*  A requirement for wild-type Ras isoforms in mutant KRas-driven signalling and transformation | Biochemical Journal
The mutant forms of KRas, NRas and HRas drive the initiation and progression of a number of human cancers, but less is known about the role of WT (wild-type) Ras alleles and isoforms in cancer. We used zinc-finger nucleases targeting HRas and NRas to modify both alleles of these genes in the mutant KRas-driven Hec1A endometrial cancer cell line, which normally expresses WT copies of these genes. The disruption of either WT isoform of Ras compromised growth-factor-dependent signalling through the ERK (extracellular-signal-regulated kinase) ...
  http://www.biochemj.org/content/452/2/313
*  OriGene - HRAS (NM 176795) cDNA Clone
HRAS - HRAS (untagged)-Human v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS), transcript variant 2 available for purchase from OriGene - Your Gene Company.
  http://www.origene.com/cdna/trueclone/accession/NM_176795/SC320717.aspx