Description of Research Expertise
Improved therapeutic response via metabolic modulation
Development of a safe and reproducible method to selectively acidify and deenergize human cancers. Specifically, we seek to employ the natural tendency of cancers to convert glucose to lactate as a method for selective intracellular acidification, which is known to potentiate tumor response to chemotherapy, radiation therapy, hyperthermia, and photodynamic therapy. In vivo 31P and 1H MRS demonstrated that human cancer xenografts such as melanoma, breast, prostate, ovarian and glioma in immunosuppressed mice treated with metabolic modulators exhibit a sustained and tumor-selective decrease in pH, bioenergetics and increase in lactate and subsequent sensitization to chemo- and radiation therapy.
Metabolic Biomarkers of Response of lymphomas
Detection of metabolic biomarkers of the response of mantle cell lymphoma (MCL) and diffuse large B cell lymphoma to Bruton’s tyrosine kinase (BTK) and mTOR inhibitors. Changes in tumor metabolism occur earlier during BTK and mTOR inhibition and are more reliable predictors of sustained response than conventional methods based on tumor volume. Lymphomas are currently staged by FDG PET/CT imaging, and therapeutic response is measured mainly by changes in tumor volume. However, kinase inhibitors are often more cytostatic than cytotoxic producing delayed changes in tumor volume.
Selected Publications
Orlovskiy S, Gupta PK, Roman J, Arias-Mendoza F, Nelson DS, Koch CJ, Narayan V, Putt ME and Nath K*: Lonidamine Induced Selective Acidification and De-Energization
of Prostate Cancer Xenografts: Enhanced Tumor Response to
Radiation Therapy Cancers 16 (1384): 2024 *Corresponding Author.
Gupta PK, Orlovskiy S, Arias-Mendoza F, Nelson DS, Osborne A, Pickup S, Glickson JD, Nath K*: Metabolic Imaging Biomarkers of Response to Signaling Inhibition Therapy in Melanoma Cancers 16 : 365,2024. *Corresponding Author.
Gupta PK, Orlovskiy S, Roman J, Pickup S, Nelson DS, Glickson JD, Nath K*: pH-dependent structural characteristics of lonidamine: (1)H and (13)C NMR study RSC Adv 13 (29): 19813-19816,2023. *Corresponding Author.
Nath K, Arias-Mendoza F, Xu HN, Gupta PK, Li LZ: Feasibility of non-invasive measurement of tumor NAD(H) by in vivo phosphorus-31 magnetic resonance spectroscopy Adv Exp Med Biol 1395 : 237-242,2022 .
Chawla, S.; Shehu, V.; Gupta, P.K.; Nath, K.; Poptani, H: Physiological Imaging Methods for Evaluating Response to Immunotherapies in Glioblastomas Int. J. Mol. Sci 22 (8): 3867,2021.
Gupta A, Nath K, Bansal N, Kumar M: Role of metabolomics-derived biomarkers to identify renal cell carcinoma: a comprehensive perspective of the past ten years and advancements Expert Review of Molecular Diagnostics 1 : 5-18,2020.
Xu HN, Feng M, Nath K, Nelson DS, Roman J, Zhao H, Lin Z, Glickson JD, Li LZ: Optical Redox Imaging of Lonidamine Treatment Response of Melanoma Cells and Xenografts Molecular imaging and biology 21 (3): 426-435,2019.
Zhou R, Bagga P, Nath K, Hariharan H, Mankoff D and Reddy R: Glutamate-weighted Chemical Exchange Saturation Transfer (GluCEST) Magnetic Resonance Imaging Detects Glutaminase Inhibition in a Mouse Model of Triple Negative Breast Cancer Cancer research 78 (19): 5521-5526,2018.
*Nath K, Roman J, Nelson DS, Guo L, Lee SC, Orlovskiy S, Muriuki K, Heitjan DF, Leeper DB, Blair IA, Putt ME, Glickson JD: Effect of Differences in Metabolic Activity of Melanoma Models on Response to Lonidamine plus Doxorubicin Scientific reports 8 (1): 14654,2018 *Corresponding Author.
*Nath K, Nelson DS, Roman J, Putt ME, Lee SC, Leeper DB, Glickson JD: Effect of Lonidamine on Systemic Therapy of DB-1 Human Melanoma Xenografts with Temozolomide Anticancer research 37 (7): 3413-3421,2017 *Corresponding Author.
*Nath K, Nelson DS, Putt ME, Leeper DB, Garman B, Nathanson KL, Glickson JD: Comparison of the Lonidamine Potentiated Effect of Nitrogen Mustard Alkylating Agents on the Systemic Treatment of DB-1 Human Melanoma Xenografts in Mice PLoS One 11 (6): e0157125,2016 *Corresponding Author.
Academic Contact Information
Perelman School of Medicine at the University of Pennsylvania
Department of Radiology
Laboratory of Molecular Imaging
B6 Blockley Hall
423 Guardian Drive
Philadelphia,
PA
19104
Phone: 215-514-9179