Targeted chemotherapy in drug-resistant tumors, noninvasive imaging of P-glycoprotein-mediated functional transport in cancer, and emerging role of Pgp in neurodegenerative diseases.
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.
Sivapackiam
Jothilingam
J
Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University Medical School, St. Louis, MO, USA.
Gammon
Seth T
ST
Harpstrite
Scott E
SE
Sharma
Vijay
V
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents