A Review and Meta-analysis on Trastuzumab Resistance in Patients with HER2+ Breast Cancer.

BACKGROUND: Trastuzumab is a monoclonal antibody that revolutionized the treatment of HER2+ breast cancer. However, about 30% of patients demonstrate resistance to this drug. OBJECTIVE: The purpose of this study is to identify the mechanisms involved in resistance to treatment. with trastuzumab in women undergoing HER2+ breast cancer treatment. METHODS: A wide review and meta-analysis were performed in the PubMed and Scielo databases up to January 2022. All articles that analyzed the efficacy of the drug in HER2+ human patients treated with trastuzumab were selected, except reviews, meta-analyses, and reports. Egger's test was applied to verify publication bias. Forest plot and PRISMA flowchart were employed. RESULTS: 60 articles were selected for the review and 15 included in the meta-analysis. A total of 102 resistance mechanisms were identified, 73 of which are different from each other. The mechanisms have been classified into 5 different categories. The main resistance mechanisms found are in the PI3K/Akt/mTOR pathway or related to low HER2, often resulting from failure to assess HER2 status. Both groups presented statistical significance. The two groups were not significantly different from each other. CONCLUSION: Drug resistance is the main challenge of trastuzumab-based treatment. To overcome this challenge, it is important to continue efforts to understand the mechanisms of cancer drug resistance, identify therapies that can treat refractory cancer to current therapies, and possibly create a panel of genes that predict resistance, avoiding symptomatic and economic costs. The main limitation of this study was the selection and population bias.

DNA barcoding reveals the mislabeling of fish in a popular tourist destination in Brazil.

The consumption of raw fish has increased considerably in the West, since it is said to be potentially healthier than processed fish (for containing omega 3 and 6, essential amino acids and vitamins). However this potential benefit, as well as the taste, value and even the risk of extinction are not the same for all species of fish, constituting grounds for fraud. Using the principles of the DNA barcode we revealed mislabelling of fish in Japanese restaurants and fishmarkets in Florianópolis, a popular tourist capital in Brazil. We sequenced the COI gene of 65 samples from fisheries and 80 from restaurants and diagnosed 30% of mislabeled samples in fisheries and 26% in restaurants. We discussed that frauds may have occurred for different reasons: to circumvent surveillance on threatened species; to sell fish with sizes smaller than allowed or abundant species as being a much rarer species (law of supply); to induce product consumption using species with better taste. It should be noted that some substitutions are derived from incorrect identification and are not a fraud per se; they are due to confusion of popular names or misunderstanding by the sellers. Therefore, we suggest the implementation of a systematic regulatory program conducted by governmental agencies to reduce mislabelling in order to avoid further damage to the community (in health and financial issues) and fish stocks.