ACT-Discover: identifying karyotype heterogeneity in pancreatic cancer evolution using ctDNA.

Background: Liquid biopsies and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution.

Strategies to design clinical studies to identify predictive biomarkers in cancer research.

The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated.

A critical review of HER2-positive gastric cancer evaluation and treatment: from trastuzumab, and beyond.

Identification of the importance of human epidermal growth factor receptor-2 (HER2) status, biomarker testing and the development of anti-HER2 treatments have changed the prognosis of breast and gastric cancers. The addition of trastuzumab to chemotherapy has improved outcomes for patients with HER2-positive metastatic adenocarcinoma of the stomach and gastroesophageal junction, but some relevant issues remain to be elucidated or will emerge with new drugs. This article reviews the current state of HER2 in gastric cancer focusing on diagnostic and anti-HER2 targeted treatment issues and the role of trastuzumab in localized disease, and its combination or integration with new therapies.

Prognostic role of host cyclooxygenase and cytokine genotypes in a Caucasian cohort of patients with gastric adenocarcinoma.

Background: Genetic factors influencing the prognosis of gastric adenocarcinoma (GAC) are not well known. Given the relevance of cytokines and other pro-inflammatory mediators in cancer progression and invasiveness, we aimed to assess the prognostic role of several functional cytokine and cyclooxygenase gene polymorphisms in patients with GAC.

Methodology: Genomic DNA from 380 Spanish Caucasian patients with primary GAC was genotyped for 23 polymorphisms in pro-inflammatory (IL1B, TNFA, LTA, IL6, IL12p40), anti-inflammatory (IL4, IL1RN, IL10, TGFB1) cytokine, and cyclooxygenase (PTGS1 and PTGS2) genes by PCR, RFLP and TaqMan assays.

Relevance of GSTM1, GSTT1, and GSTP1 gene polymorphisms to gastric cancer susceptibility and phenotype.

Human glutathione S-transferases (GSTs) are phase II metabolizing enzymes that play a key role in protecting against cancer by detoxifying numerous potentially cytotoxic/genotoxic compounds. The genes encoding the human GST isoenzymes GSTM(mu)1, GSTT(theta)1 and GSTP(pi)1 harbour polymorphisms, which have been considered important modifiers of the individual risk for environmentally induced cancers such as gastric cancer (GC). However, results are inconsistent among studies from different geographic areas and ethnic groups.

SEOM clinical guidelines for using molecular markers in clinical practice.

Nowadays, treatment selection for most types of cancers is based on anatomical, histological and clinical criteria, which are defi ned by the selection criteria used in registration phase III trials. However, different cancers present distinct molecular features, so the current approach results in a lack of specificity of cancer therapy, which is associated with decreased efficacy and unnecessary toxicities and costs. Molecular diagnostics has proved able to predict the efficacy of selected targeted therapies.

Serum markers and prognosis in locally advanced breast cancer.

Background: Locally advanced breast cancer (LABC) represents a heterogeneous subgroup of breast cancer with an often dismal outcome. Identifying prognostic factors has acquired great significance for the selection of optimal treatment in individual patients.

Methods: Between January 1993 and December 1997, 103 patients were treated in our institution with multimodality treatment consisting of neoadjuvant chemotherapy followed by surgery, adjuvant chemotherapy and radiotherapy; tamoxifen was added in hormone receptor-positive cases.

Toxic epidermal necrolysis in patients receiving anticonvulsants and cranial irradiation: a risk to consider.

Toxic epidermal necrolysis (TEN) is an infrequent disease but with a high mortality rate. It is a mucocutaneous reaction resulting from hypersensitivity to a variety of agents including most anticonvulsants. Many patients with primary or metastatic intracranial tumours receive anticonvulsants for seizure prophylaxis despite their efficacy not having been clearly demonstrated.