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• W2464567583 abstract "In the last few years, technical development of sequencing technologies has made comprehensive genetic analysis available for clinical routine. In addition, collaborative projects such as The Cancer Genomic Atlas (TCGA) have performed comprehensive molecular analyses in a large number of various tumors and made their huge data sets available to the wider research community. This has provided insight into the molecular architecture of the most prevalent tumors and led to the identification of numerous therapeutically relevant, targetable genetic alterations. As a consequence, current cancer treatment is rapidly shifting from empirical therapy with cytotoxic anticancer drugs to rationale-based, genotype-directed therapy using molecular targeted agents. This is especially true for rare tumors, for which recommendations for empirical therapies are often missing because of a lack of prospective randomized studies. In this issue of European Urology, Collazo-Lorduy et al. [1] report on a patient with urachal adenocarcinoma (UrC) who was treated using a genotype-directed treatment strategy. After failure of two lines of cytotoxic chemotherapy, targeted and whole-exome sequencing of archival primary tumor tissue revealed the presence of EGFR amplification and the absence of KRAS, NRAS, and BRAF mutations. EGFR overexpression is a potential positive predictor, while activating KRAS, NRAS, and BRAF mutations are negative predictors for anti-EGFR therapy. On the basis of this genetic constellation, patient was treated with anti-EGFR therapy resulting in a durable partial response for 8 mo, indicating clear activity in this case with strong disease progression. This observation is in line with a study by Goss et al. [2], who administered gefitinib (another anti-EGFR agent) to 28 patients with various solid tumors including breast, colon, cervix, and ovary cancers, as well as one patient with lymph node metastatic UrC. Notably, the most significant decrease in tumor size was observed in the UrC patient. This radiographic response was accompanied by a biological response, as evidenced by a significant decrease in Ki67 proliferation index on post-treatment tumor biopsy. These data together indicate the potential beneficial effect of antiEGFR therapy in UrC. UrC is an extremely rare cancer, frequently detected by its invasion of the urinary bladder on progression, when systemic therapy is required. Because of its low incidence, clinical evidence regarding systemic treatment of cases with disease progression is lacking, which is reflected in the heterogeneity of treatment decisions. A proportion of UrC patients — similar to urothelial bladder cancer — receive cisplatin-based regimens, while others are treated with 5-fluorouracil (5-FU)–containing therapy, which is used as standard in colorectal cancer (CRC). The first strategy considers the predominant urinary bladder involvement of UrC, while the second is based on the known histologic similarity between UrC and CRC. Comparison of mutational patterns between various cancers may provide further valuable information for therapeutic decision-making. Next-generation sequencing technologies provided the opportunity for extensive genomic comparisons between different tumor entities and opened the way for genomic/ molecular tumor taxonomy. In this context, genetic" @default.
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• W2464567583 date "2016-11-01" @default.
• W2464567583 modified "2023-10-17" @default.
• W2464567583 title "Clinical Sequencing-guided Therapy of Urachal Carcinoma: New Perspective for a Rare Cancer" @default.
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• W2464567583 doi "https://doi.org/10.1016/j.eururo.2016.07.004" @default.
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