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Free Content Editorial [Hot Topic: Ion Channels and Cancers (Guest Editor: Robert Kiss)]

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Despite worldwide research and major development efforts in oncology therapeutics, approximately 50% of cancer patients remain associated with dismal prognoses. More than 85% of the current chemotherapeutics that are used by oncologists to fight cancer are proapoptotic agents; however these cancers display intrinsic resistance to pro-apoptotic stimuli. In addition, metastatic cancer cells are naturally resistant to pro-apoptotic agents because they must resist ano├»kis during their metastatic progression. Another major obstacle to the effective treatment of cancer is multidrug resistance (MDR), which is exhibited by many cancers and is either an intrinsic property of certain cancers or an acquired property during chronic chemotherapy. Recent published data indicate several findings: i) various cancer cell types overexpress specific ion channels compared to the respective normal cells that are derived from the same tissue and ii) inhibition of these overexpressed ion channels can be detrimental for these cancer cells. The current special issue entitled “Ion Channels and Cancers” provides an overview of this novel and exciting findings to combat cancers that are associated with dismal prognoses and reveals a large set of chemical families that could be derivatized / optimized to specifically target overexpressed ion channels in cancers.

Robert Kiss and colleagues contribute a review entitled “Targeting the Na+/K+-ATPase to combat multidrug resistant (MDR) cancers and/or cancers displaying intrinsic resistance to pro-apoptotic stimuli”. This review provides an overview about the types of cancers that overexpress the Na+/K+-ATPase (NaK) and an in-depth discussion on the structure-activity-relationship (SAR) between NaK and its ligands (cardenolides versus bufadienolides) that display anticancer activities in vitro and in vivo, including in cancer patients.

Christian Stock and colleagues present a review entitled “Is the multifunctional Na+/H+ exchanger isoform 1 a potential therapeutic target in cancer?”.

The Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitously expressed transporter that mediates many physiological tasks in the cell. NHE1 is upregulated and/or overexpressed in a number of tumor cells. In many cases, elevated NHE1 activity correlates with increased cell motility and malignancy. In the current article, different NHE1 inhibitors are compared, and possible clinical exploitations of NHE1 inhibition are discussed.

Antonio Felipe and colleagues provide a review entitled “Targeting the voltage-dependent K+ channels Kv1.3 and Kv1.5 as tumor biomarkers for cancer detection and prevention”. This article discusses potassium channels (KChs) and focuses on the largest sub-group of voltage-dependent potassium (Kv) channels. Many studies have reported the involvement of KChs in cancer progression. The current article demonstrates that the expression patterns of Kv1.3 and Kv1.5 are remodeled in cancers. Unlike Kv1.5, Kv1.3 is characterized by a selective and potent pharmacology, which may lead to specific pharmacological targeting in specific types of cancers.

Luis Pardo and colleagues contribute a review entitled “Diagnostic and therapeutic approaches targeting KV10.1 open a novel therapeutic window”. KV10.1 is ectopically expressed in the majority of solid tumors. Due to its cell-surface accessibility, KV10.1 may be potentially used for tumor treatment and diagnosis. The current article provides an overview of the current data linking KV10.1 to cancer and proposes strategies that are suitable for the design of KV10.1-targeted drugs with a wider therapeutic window.

Annarosa Arcangeli and colleagues enclose a review entitled “Targeting ion channels in leukemias: a new challenge for treatment”. This article focuses on Kv11.1 (also known as hERG1), a Kv channel that modulates cell adhesion to the extracellular matrix (ECM). Kv11.1 forms multiprotein membrane complexes with integrin receptors in acute myeloid leukemias (AML) and acute lymphoblastic leukemias (ALL). Blocking Kv11.1 in mice has a protective effect in acute leukemias. In ALL cells, hERG1 inhibitors abrogate the protective effect of bone marrow stromal cells and enhance the cytotoxicity of some common antileukemic drugs. The current review focuses on how ion channel modulators overcome chemoresistance in acute leukemias.....

Document Type: Research Article


Publication date: February 1, 2012

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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