title: Targeted chemotherapy in drug-resistant tumors, noninvasive imaging of P-glycoprotein-mediated functional transport in cancer, and emerging role of Pgp in neurodegenerative diseases.
abstract: Multidrug resistance (MDR) mediated by overexpression of P-glycoprotein (Pgp) is one of the best characterized transporter-mediated barriers to successful chemotherapy in cancer patients and is also a rapidly emerging target in the progression of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Therefore, strategies capable of delivering chemotherapeutic agents into drug-resistant tumors and targeted radiopharmaceuticals acting as ultrasensitive molecular imaging probes for detecting functional Pgp expression in vivo could be expected to play a vital role in systemic biology as personalized medicine gains momentum in the twenty-first century. While targeted therapy could be expected to deliver optimal doses of chemotherapeutic drugs into the desired targets, the interrogation of Pgp-mediated transport activity in vivo via noninvasive imaging techniques (SPECT and PET) would be beneficial in stratification of patient populations likely to benefit from a given therapeutic treatment, thereby assisting management of drug resistance in cancer and treatment of neurodegenerative diseases. Both strategies could play a vital role in advancement of personalized treatments in cancer and neurodegenerative diseases. Via this tutorial, authors make an attempt in outlining these strategies and discuss their strengths and weaknesses.
authors: Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University Medical School, St. Louis, MO, USA.
authors: Jothilingam
authors: J
authors: Sivapackiam
authors: Seth T
authors: ST
authors: Gammon
authors: Scott E
authors: SE
authors: Harpstrite
authors: Vijay
authors: V
authors: Sharma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D018450:Disease Progression; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D057054:Molecular Imaging / Q000379:methods*; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents