title: Genomics and cancer drug resistance.
abstract: Cellular drug resistance is a major obstacle in cancer therapy. Mechanisms of resistance can be associated with altered expression of ATP-binding cassette (ABC) family of transporters on cell membrane transporters, the most common cause of multi-drug resistance (MDR), but can also include alterations of DNA repair pathways, resistance to apoptosis and target modifications. Anti-cancer treatments may be divided into different categories based on their purpose and action: chemotherapeutic agents damage and kill dividing cells; hormonal treatments prevent cancer cells from receiving signals essential for their growth; targeted drugs are a relatively new cancer treatment that targets specific proteins and pathways that are limited primarily to cancer cells or that are much more prevalent in cancer cells; and antibodies function by either depriving the cancer cells of necessary signals or by causing their direct death. In any case, resistance to anticancer therapies leads to poor prognosis of patients. Thus, identification of novel molecular targets is critical in development of new, efficient and specific cancer drugs. The aim of this review is to describe the impact of genomics in studying some of the most critical pathways involved in cancer drug resistance and in improving drug development. We shall also focus on the emerging role of microRNAs, as key gene expression regulators, in drug resistance. Finally, we shall address the specific mechanisms involved in resistance to tyrosine kinase inhibitors in chronic myeloid leukemia.
authors: CIGMH - Department of Genetics, Universidade Nova de Lisboa, Lisboa, Portugal. seba.gene@fcm.unl.pt
authors: Antonio S
authors: AS
authors: Rodrigues
authors: Joana
authors: J
authors: Dinis
authors: Marta
authors: M
authors: Gromicho
authors: Celia
authors: C
authors: Martins
authors: Antonio
authors: A
authors: Laires
authors: Jose
authors: J
authors: Rueff
mesh_terms: D055808:Drug Discovery / Q000379:methods; D019008:Drug Resistance, Neoplasm; D023281:Genomics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*