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Article
Open AccessTargeted therapy of pyrrolo[2,3-d]pyrimidine antifolates in a syngeneic mouse model of high grade serous ovarian cancer and the impact on the tumor microenvironment
Novel therapies are urgently needed for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. In addition, therapies that target unique vulnerabilities in the tumor microenvironment (TME) of...
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Article
Lipid metabolism reprogramming in renal cell carcinoma
Metabolic reprogramming is recognized as a hallmark of cancer. Lipids are the essential biomolecules required for membrane biosynthesis, energy storage, and cell signaling. Altered lipid metabolism allows tumo...
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Article
Open AccessFolate transporter dynamics and therapy with classic and tumor-targeted antifolates
There are three major folate uptake systems in human tissues and tumors, including the reduced folate carrier (RFC), folate receptors (FRs) and proton-coupled folate transporter (PCFT). We studied the function...
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Article
Open AccessImpact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds
Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation.
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Article
Open AccessFolate receptors and transporters: biological role and diagnostic/therapeutic targets in cancer and other diseases
Folate receptors and transporters and one-carbon metabolism continue to be important areas of study given their essential roles in an assortment of diseases and as targets for treatment of cancer and inflammat...
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Article
Open AccessChronic p27Kip1 Induction by Dexamethasone Causes Senescence Phenotype and Permanent Cell Cycle Blockade in Lung Adenocarcinoma Cells Over-expressing Glucocorticoid Receptor
Dexamethasone (Dex), co-administered to lung adenocarcinoma patients with pemetrexed chemotherapy, protects against pemetrexed cytotoxicity by inducing reversible G1 arrest, reflected by the effect of Dex on F...
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Article
The promise and challenges of exploiting the proton-coupled folate transporter for selective therapeutic targeting of cancer
This review considers the “promise” of exploiting the proton-coupled folate transporter (PCFT) for selective therapeutic targeting of cancer. PCFT was discovered in 2006 and was identified as the principal fol...
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Article
Therapeutic targeting malignant mesothelioma with a novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate via its selective uptake by the proton-coupled folate transporter
We examined whether the novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate, compound 2, might be an effective treatment for malignant pleural mesothelioma (MPM), reflecting its selective membrane tr...
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Chapter
Biological Role, Properties, and Therapeutic Applications of the Reduced Folate Carrier (RFC-SLC19A1) and the Proton-Coupled Folate Transporter (PCFT-SLC46A1)
The mechanisms by which folates are transported across cell membranes have been an area of research interest for nearly five decades. Major transport systems include the facilitative carriers, the reduced fola...
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Chapter
Discovery of Novel Antifolate Inhibitors of De Novo Purine Nucleotide Biosynthesis with Selectivity for High Affinity Folate Receptors and the Proton-Coupled Folate Transporter Over the Reduced Folate Carrier for Cellular Entry
Lack of drug selectivity is one of the major causes of the failure of cancer chemotherapy. This Chapter describes studies that explore the concept of therapeutic targeting solid tumors using folate-receptor (F...
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Article
Preface
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Article
Human reduced folate carrier: translation of basic biology to cancer etiology and therapy
This review attempts to provide a comprehensive overview of the biology of the physiologically and pharmacologically important transport system termed the “reduced folate carrier” (RFC). The ubiquitously expre...
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Protocol
Structural Determinants of Folate and Antifolate Membrane Transport by the Reduced Folate Carrier
Besides its important role in folate homeostasis, membrane transport is a critical determinant of the antitumor activities of antifolate therapeutics used in cancer chemotherapy, such as methotrexate (MTX) and an...
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Chapter
Determinants of the Disparate Antitumor Effects of (6R)5,10-Dideaza-5,6,7,8-Tetrahydrofolate and Methotrexate Toward Methotrexate Resistant CCRF-CEM Cells, Characterized by Severely Impaired Antifolate Membrane Transport
The antifolate, (6R) 5,10-dideaza-5,6,7,8-tetrahydrofolate (DDATHF), derives its antitumor effects by inhibiting 5’-phosphoribosylglycinamide (GAR) transformylase1, the first folate-dependent enzyme in the de nov...
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Chapter
Biochemical Rationale for Selectivity in the Modulation of Methotrexate Activity During Leucovorin Rescue or Early Nucleoside Protection
The first successful modulation of the selectivity of an antineoplastic agent was demonstrated by Goldin and his coworkers in the 1950 ’s with the leucovorin rescue phenomenon as an approach to the enhancement...
