Comparison of plasma ctDNA and tissue/cytology-based techniques for the detection of EGFR mutation status in advanced NSCLC: Spanish data subset from ASSESS.

PURPOSE: The analysis of epidermal growth factor receptor (EGFR) mutations in many patients with advanced non-small-cell lung cancer (aNSCLC) has provided the opportunity for successful treatment with specific, targeted EGFR tyrosine kinase inhibitors. However, this therapeutic decision may be challenging when insufficient tumor tissue is available for EGFR mutation testing. Therefore, blood surrogate samples for EGFR mutation analysis have been suggested. METHODS: Data were collected from the Spanish cohort of patients in the large, non-interventional, diagnostic ASSESS study (NCT01785888) evaluating the utility of circulating free tumor-derived DNA from plasma for EGFR mutation testing. The incidence of EGFR mutation in Spain and the level of concordance between matched tissue/cytology and plasma samples were evaluated. RESULTS: In a cohort of 154 eligible patients, EGFR mutations were identified in 15.1 and 11.0% of tumor and plasma samples, respectively. The most commonly used EGFR mutation testing method for the tumor tissue samples was the QIAGEN Therascreen® EGFR RGQ PCR kit (52.1%). Fragment Length Analysis + PNA LNA Clamp was used for the plasma samples. The concordance rate for EGFR mutation status between the tissue/cytology and plasma samples was 88.8%; the sensitivity was 45.5%, and the specificity was 96.7%. CONCLUSIONS: The high concordance between the different DNA sources for EGFR mutation testing supports the use of plasma samples when tumor tissue is unavailable.

Production of fructanase by a wild strain of Saccharomyces cerevisiae on tequila agave fructan.

A new wild strain of Saccharomyces cerevisiae (CF3) isolated from tequila must was evaluated for production of fructanase on Agave tequilana Weber fructan (FT). Fructanase activity (F) was assessed by a 3(3) factorial design (substrate, temperature and pH). High enzymatic activity (31.1 U/ml) was found at 30 °C, pH 5, using FT (10 g/l) as substrate. The effect of initial substrate concentration on F (FT0, 5.7-66 g/l) was studied and it was found that F was highest (44.8 U/ml) at FT0 25 g/l. A 2(2) factorial experimental design with five central points was utilized to study the effect of stirring and aeration on fructanase activity; stirring exhibited a stronger effect on F. The ratio fructanase to invertase (F/S) was 0.57, which confirms that the enzymes are fructanase. Crude fructanase reached high substrate hydrolysis (48 wt%) in 10 h. It is shown that S. cerevisiae CF3 was able to produce large amounts of fructanase by growing it on fructan from A. tequilana.

C-MET as a new therapeutic target for the development of novel anticancer drugs.

MET is a tyrosine kinase receptor that, upon binding of its natural ligand, the hepatocyte growth factor (HGF), is phosphorylated and subsequently activates different signalling pathways involved in proliferation, motility, migration and invasion. MET has been found to be aberrantly activated in human cancer via mutation, amplification or protein overexpression. MET expression and activation have been associated with prognosis in a number of tumour types and predict response to MET inhibitors in preclinical models. Here we review the HGF/MET signalling pathway, its role in human cancer and the different inhibitory strategies that have been developed for therapeutic use.

Aromatase inhibitors and male breast cancer.

The majority of breast cancers in male patients are hormone receptor positive. Tamoxifen has proven to be successful in both adjuvant and metastatic settings and remains the standard of care. Given the improved outcomes in female patients with aromatase inhibitors (AI), these drugs have become a potential therapeutic tool for male patients. Preliminary data show effective suppression of oestradiol levels in males treated with AI and some reports have demonstrated objective responses. Here we report a case of a male patient with metastatic breast cancer treated with letrozole who achieved clinical response associated with a decrease in blood oestradiol levels.

p53 protein overexpression and response to induction chemoradiation therapy in patients with locally advanced rectal adenocarcinoma.

BACKGROUND: The association between mutations in the p53 gene and prognosis in colorectal cancer remains controversial. This report evaluates the role of p53 protein to predict the response of neoadjuvant chemoradiation therapy in patients with primary locally advanced rectal adenocarcinoma. METHODS: Between January 1993 and December 1994, 26 patients were seen with locally advanced primary rectal adenocarcinoma, located between 0 and 10 cm from the anal verge, demonstrated clinically and by CT scan. Each received 45 Gy of preoperative radiation therapy (RT) concomitantly with bolus infusion of 5-fluorouracil (5-Fu) (450/mg/m2 on days 1 to 5 and 28 to 33 of RT). Surgery was performed between 4 and 8 weeks later. All the primary tumors were mapped and sliced. The response rate was divided according to the percentage of malignant cells in the rectal wall and perirectal fat. Lymph nodes were studied with the manual or modified clearing technique. p53 mutant status was assessed immunohistochemically from sections of the formalin-fixed, paraffin-embedded pretreatment biopsy and the resected specimen. RESULTS: There were 14 females and 12 males, with a mean age of 54 years. All received the scheduled treatment. An abdominoperineal resection (n = 10), low anterior resection (n = 10), and pelvic exenteration (n = 6) were performed. The stages of tumors were as follows: no residual tumor (n = 4); T2 (n = 6); T3-4 (N = 9); and T3-4, N1,2 (n = 7). Fourteen specimens (54%) had mutated p53, and 10 (71%) had >50% of residual tumor, whereas only two (17%) of the specimens with normal p53 had >50% of residual tumor (P = .018). Eight of the 10 low anterior resections were performed in patients whose specimens expressed normal p53. CONCLUSION: Our results suggest that the determination of p53 is a factor in predicting tumor response in patients who undergo preoperative chemoradiation therapy for rectal adenocarcinoma.