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• W2024886071 abstract "Targeted therapy is the “holy grail” sought to achieve efficacy and reduce toxicity in cancer treatment. It is difficult nowadays to avoid reference to the word “targeted” or “personalized” in publications describing “novel” strategies for treating cancer. During the last decade, spectacular advances in genomics have brought the realization of targeted therapy closer to the bedside in treating patients with hematologic and solid tumors. Remarkable progress based on our understanding of aberrant genes and signaling has led to novel strategies for targeted therapy, understanding efficacy in select patients, and possible mechanisms leading to development of resistance. However, the absence of durable responses, rapid development of resistance to treatment, and dose limiting toxicity continue to be major hurdles that hamper progress. The focus of this seminar in Urologic Oncology is certainly timely given the availability of drugs and pathways that can be targeted in the treatment of urologic malignancies. To accompany this article, we have 2 excellent essays that provide a comprehensive and informative review on the current status and the future of targeted therapy in bladder cancer and renal cancer. Although it is unfortunate that we do not have an essay on prostate cancer where targeted therapy has led to remarkable progress in the clinical management of metastatic disease, in this editorial, the theme of targeted therapy in prostate cancer is addressed because evolving paradigms with this disease are relevant in understanding why we have successes or failures. Although chemotherapy with classical cytotoxic drugs does not often directly address putative drug targets that govern efficacy or toxicity in therapy, targeting of specific aberrant genes/pathways with small molecule inhibitors in cancer represents a more rational approach. However, similar to chemotherapy with cytotoxic drugs, presence of a presumed target per se does not necessarily assure efficacy, and we face similar problems with several of the small molecule–targeted drugs that are active clinically in select malignancies. Moreover, in this era of targeted therapy, the age-old problem of “intrinsic” and “acquired resistance” is an issue that continues to be poorly understood. Drugs that target specific mutations can be aided with a companion test to achieve selectivity, but this luxury does not exist with aberrant signaling pathways, e.g., angio" @default.
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• W2024886071 date "2014-01-01" @default.
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• W2024886071 title "Pharmacogenomics: New paradigms for targeted therapy based on individual response to drugs" @default.
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• W2024886071 doi "https://doi.org/10.1016/j.urolonc.2013.08.027" @default.
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