Search results for "Oncogene"

Tumour Shrinkage and Response Outcomes During Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment

2014

ABSTRACT Aim: Tumour shrinkage/response are important outcomes for patients (pts) with metastatic colorectal cancer (mCRC) as they may delay progression and ultimately improve survival. Here we report tumour response data for pts with RAS WT mCRC treated with FOLFIRI ± pmab. Methods: 181 was a phase 3 randomised study of second-line pmab + FOLFIRI vs FOLFIRI alone in pts with previously treated mCRC. KRAS exon 2 wild-type (WT) samples from this study were tested for mutations in KRAS exons 3/4 and NRAS exons 2/3/4 via bidirectional Sanger sequencing and WAVE-based SURVEYOR® to identify pts with RAS WT tumours (no mutations in KRAS/NRAS exons 2, 3 or 4). Objective response rates (ORRs) and m…

KRAS/NRAS and BRAF Mutations in the 20050181 Study of Panitumumab + FOLFIRI for the 2ND-Line Treatment of Metastatic Colorectal Cancer: Updated Analy…

2014

Validation of the High-Risk Prognostic Score Defined By the Presence of Mutations in NRAS or TP53 in a Cohort of 497 Patients with Acute Myeloid Leuk…

2020

INTRODUCTION Older AML patients have a different mutational landscape compared to younger patients. The prognostic classification of AML proposed by the European Leukemia Net (2017) is based on the presence of mutations in FLT3 (ITD), NPM1, CEBPA, RUNX1, ASXL1 and TP53. However, our group has identified a high-risk prognostic score in older patients with AML, who are undergoing treatment with azacitidine or low-dose cytarabine plus fludarabine, which predict a shorter survival. OBJECTIVE Validation of the previously identified high-risk prognostic score, defined by the presence of mutations in NRAS or TP53, in 3 cohorts of patients with AML who have been studied by NGS with a custom panel i…

Peripheral neuroblastic tumors with genotype-phenotype discordance: A report from the Children's Oncology Group and the International Neuroblastoma P…

2012

Background Of 4,706 peripheral neuroblastic tumors (pNTs) registered on the Children’s Cancer Group and Children’s Oncology Group Neuroblastoma Study between 1989 and 2010, 51 cases (1.1%) had genotype-phenotype discordance characterized by MYCN amplification (indicating poor prognosis) and Favorable Histology (indicating better prognosis).

Integrative clinical transcriptome analysis reveals TMPRSS2-ERG dependency of prognostic biomarkers in prostate adenocarcinoma.

2019

In prostate adenocarcinoma (PCa), distinction between indolent and aggressive disease is challenging. Around 50% of PCa are characterized by TMPRSS2‐ERG (T2E)‐fusion oncoproteins defining two molecular subtypes (T2E‐positive/negative). However, current prognostic tests do not differ between both molecular subtypes, which might affect outcome prediction. To investigate gene‐signatures associated with metastasis in T2E‐positive and T2E‐negative PCa independently, we integrated tumor transcriptomes and clinicopathological data of two cohorts (total n = 783), and analyzed metastasis‐associated gene‐signatures regarding the T2E‐status. Here, we show that the prognostic value of biomarkers in PCa…

Radiotherapy with BRAF inhibitor therapy for melanoma: progress and possibilities.

2015

The introduction of small molecule BRAFV600 kinase inhibitors represents a milestone in the targeted therapy of patients with metastatic melanoma by a significant increase in therapeutic efficacy in terms of overall and progression-free survival compared with conventional chemotherapy. Beside BRAFV600 inhibitor treatment, radiotherapy is a further mainstay for the therapy of metastatic melanoma and thus a concomitant or sequential application of BRAFV600 inhibitors and radiotherapy is inevitable. Recent reports show a significant radiosensitization of the irradiated healthy tissue in patients with melanoma after the combination of radiotherapy and BRAFV600 inhibitors, evoking concern in cl…

Pharmacogenomics of cetuximab in metastatic colorectal carcinoma

2014

Cetuximab is a chimeric monoclonal antibody that has revolutionized the treatment of metastatic colorectal cancer. Knowledge of the mechanisms that underlie its effectiveness, as well as the primary and secondary resistance mechanisms, have led to important developments in the understanding of cetuximab biology. In light of knowledge gained from recent trials, the efficacy of cetuximab has been clearly demonstrated to depend upon RAS mutational status, moreover cetuximab should only be used in a subset of patients who may benefit. In this article, we critically review clinical and pharmacogenetic issues of cetuximab, focusing on the cost–effectiveness involved with the use of the drug.

The prevalent KRAS exon 2 c.35 G > A mutation in metastatic colorectal cancer patients: a biomarker of worse prognosis and potential benefit of bevac…

2015

Bevacizumab-containing chemotherapy differently predict increased efficacy in KRAS exon 2 mutant and wild-type metastatic colorectal cancer (MCRC) patients. Mutant compared to wild-type status did not significantly affect progression-free survival (PFS) and overall survival (OS) in patients fit for first line bevacizumab-containing FIr-B/FOx regimen, and after progression. In patients unfit for intensive regimens, mutant status significantly affected PFS, while not OS. Codon 12 KRAS mutations differentially affect GTPase function, and confer worse clinical behaviour. Prognostic relevance of the prevalent c.35 G. >. A KRAS mutation was retrospectively evaluated. Fit c.35 G. >. A mutant patie…

New molecular targets in bone metastases.

2010

Bone metastases have a major impact on morbidity and on mortality in cancer patients. Despite its clinical relevance, metastasis remains the most poorly elucidated aspect of carcinogenesis. The biological mechanisms leading to bone metastasis establishment have been referred as " vicious circle," a complex network between cancer cells and the bone microenvironment. This review is aimed to underline the new molecular targets in bone metastases management other than bisphosphonates. Different pathways or molecules such as RANK/RANKL/OPG, cathepsin K, endothelin-1, Wnt/DKK1, Src have recently emerged as potential targets and nowadays preclinical and clinical trials are underway. The results fr…

Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clin…

2014

Abstract: Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of 'oncogene addiction', with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment. Some studies evaluated the main differences between these drugs both for direct comp…