Overcoming nucleoside analog chemoresistance of pancreatic cancer: A therapeutic challenge

Mechanisms of Overcoming Intrinsic Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma through the Redox Modulation

“…The failure is attributable to many factors, including extrinsic (6) or intrinsic (7) resistance to the conventional therapeutic approaches of chemotherapy. The chemotherapeutic agent gemcitabine is usually the recommended first-line drug for patients with PDAC and is given alone or in combination with other agents (8). Unfortunately, a large number of patients are resistant to these therapies mainly because the dense tumor stroma functions as a barrier and extrinsic resistance (7).…”

Inhibitory effect of geraniol in combination with gemcitabine on proliferation of BXPC-3 human pancreatic cancer cells

“…1,2 The response rate of gemcitabine is <20%, however, due to the acquired or inherent drug resistance of pancreatic cancer cells, which results in poor therapeutic outcomes. [3][4][5][6] Geraniol is a natural acyclic monoterpene isolated from plants of Pelargonium, Cymbopogon spreng, Lauraceae Litsea and Rosaceae. 7 Geraniol is categorized as 'Generally Recognized as Safe' by the United States Food and Drug Administration for use as a food additive and insect repellent, and shows several pharmacological effects including inhibition of proliferation and growth in cancer cells and prevention of hepatotoxicity.…”

Molecular Imaging of Membrane Transporters’ Activity in Cancer: a Picture is Worth a Thousand Tubes

“…Tumors may also be poorly penetrable by drugs because of a massive stromal component and physical distance from blood vessels (9). Tumor cells themselves express a variety of uptake and efflux transporters which can affect the cellular distribution of drugs and probes and contribute to the development of drug resistance (1)(2)(3)(4). The majority of these transporters are also expressed in normal tissues involved in systemic drug disposition, such as the intes-tine, the liver, the kidneys, and the capillary endothelial cells that form the blood brain barrier (10,11).…”

“…Changes in transporter expression and their functional activity may result in altered uptake of nutrients by tumor cells and can also affect the distribution of chemotherapeutic drugs into their targets within tumors (1)(2)(3)(4). Hence, assessing transporter-related processes can potentially assist in tumor localization, monitoring, and predicting response to therapy and in drug development.…”