Evidence map›Paper›PMID 39984334›Full record

ArticleAcademic radiology2026

MRS and Optical Imaging Studies of Therapeutic Response to Combination Therapy Targeting BRAF/MEK in Murine Melanomas.

Pradeep Kumar Gupta, Lin Z Li, Dinesh Kumar Singh, Skyler Nova, Fernando Arias-Mendoza, Stepan Orlovskiy, Sanjeev Chawla, David S Nelson, Michael D Farwell, Kavindra Nath

Abstract read
In one paragraph

Article in Academic radiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Pradeep Kumar GuptaDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.K.G., L.Z.L., D.K.S., S.N., F.A.M., S.O., S.C., D.S.N., M.D.F., K.N.).
Lin Z LiDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.K.G., L.Z.L., D.K.S., S.N., F.A.M., S.O., S.C., D.S.N., M.D.F., K.N.); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (L.Z.L., K.N.); Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania (L.Z.L., K.N.).
Dinesh Kumar SinghDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.K.G., L.Z.L., D.K.S., S.N., F.A.M., S.O., S.C., D.S.N., M.D.F., K.N.).
Skyler NovaDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.K.G., L.Z.L., D.K.S., S.N., F.A.M., S.O., S.C., D.S.N., M.D.F., K.N.).
Fernando Arias-MendozaDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.K.G., L.Z.L., D.K.S., S.N., F.A.M., S.O., S.C., D.S.N., M.D.F., K.N.); Advanced Imaging Research, Inc. Cleveland, Ohio (F.A.M.).
Stepan OrlovskiyDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.K.G., L.Z.L., D.K.S., S.N., F.A.M., S.O., S.C., D.S.N., M.D.F., K.N.).
Sanjeev ChawlaDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.K.G., L.Z.L., D.K.S., S.N., F.A.M., S.O., S.C., D.S.N., M.D.F., K.N.).
David S NelsonDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.K.G., L.Z.L., D.K.S., S.N., F.A.M., S.O., S.C., D.S.N., M.D.F., K.N.).
Michael D FarwellDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.K.G., L.Z.L., D.K.S., S.N., F.A.M., S.O., S.C., D.S.N., M.D.F., K.N.).
Kavindra NathDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.K.G., L.Z.L., D.K.S., S.N., F.A.M., S.O., S.C., D.S.N., M.D.F., K.N.); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (L.Z.L., K.N.); Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania (L.Z.L., K.N.). Electronic address: Kavindra.Nath@pennmedicine.upenn.edu.

Funding

Phenotypic Diversity in COVID-19UL1TR001878 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2016 to 2025
$102.4M
Metabolic Imaging of Targeted Therapies in CancerR01CA268601 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Kavindra Nath, MARIUSZ A. WASIK · 2022 to 2026
$3.0M
Label-Free Optical Redox Imaging for Pretreatment Prognosis of Early-Stage Triple Negative Breast CancerR01CA277037 · NCI · UNIVERSITY OF PENNSYLVANIA · PI LIN Z LI · 2023 to 2026
$2.6M
Metabolic Biomarkers of Response of Mantle Cell Lymphoma to Bruton Tyrosine Kinase InhibitionR01CA228457 · NCI · UNIVERSITY OF PENNSYLVANIA · PI NATH, KAVINDRA, WASIK, MARIUSZ A. · 2020 to 2024
$2.5M
Melanoma: Metabolic Biomarkers of Response to Targeted TherapyR01CA250102 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BLAIR, IAN ALEXANDER, NATH, KAVINDRA · 2020 to 2024
$2.4M
Translation of Noninvasive Metabolic Biomarkers to Targeted Therapy for CancerR21CA280523 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ARIAS-MENDOZA, FERNANDO, NATH, KAVINDRA · 2024 to 2025
$418k
NCATS NIH HHS UL1 TR001878NCI NIH HHS R01 CA228457NCI NIH HHS R01 CA250102NCI NIH HHS R01 CA268601NCI NIH HHS R01 CA277037NCI NIH HHS R21 CA280523
6 · The paper itself

Abstract

RATIONALE AND

objectivesMelanoma, an aggressive skin cancer, often harbors BRAFV600E mutations driving tumor progression via the mitogen-activated protein kinase (MAPK) pathway. While targeted therapies like BRAF (dabrafenib) and MEK (trametinib) inhibitors have improved outcomes, resistance linked to metabolic reprogramming remains a challenge. This study investigates metabolic changes induced by dual BRAF/MEK inhibition in a BRAFV600E-mutant murine melanoma model using magnetic resonance spectroscopy (MRS), optical redox imaging (ORI), and biochemical assays. We aim to identify metabolic biomarkers for predicting therapeutic response or resistance. MATERIALS AND

methodsYUMM1.7 murine melanoma cells and tumored mice were treated with dabrafenib and trametinib. ORI assessed mitochondrial redox status by measuring reduced nicotinamide adenine dinucleotide (NADH), oxidized flavoproteins (Fp), and the redox ratio (Fp/(NADH+Fp)) in vitro. Glucose consumption and lactate production were analyzed using a YSI Biochemical Analyzer. In vivo metabolic changes were monitored via ¹H and ³¹P MRS, evaluating lactate, alanine, pH, βNTP/Pi, and total NAD(P)(H), which represents combined oxidized nicotinamide adenine dinucleotide (NAD

resultsUnder the combined therapeutic regimen of dabrafenib and trametinib, YUMM1.7 murine melanoma cells exhibited significant inhibition of lactate generation, non-significant reduction of glucose utilization, decreased intracellular levels of NADH and total NAD(P)(H), and more oxidized redox status in vitro, which can be interpreted as inhibition of the Warburg effect and improved OXPHOS efficiency by targeting BRAF/MEK signaling activities. Furthermore, YUMM1.7 mouse tumors demonstrated less tissue acidification and improved bioenergetics (βNTP/Pi), in agreement with the in vitro data.

conclusionMRS, ORI, and biochemical assays identified critical metabolic changes, highlighting potential biomarkers and supporting the integration of metabolic inhibitors with MAPK-targeted therapies to improve clinical outcomes.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsMelanomaMelanoma, ExperimentalOptical ImagingProto-Oncogene Proteins B-rafSkin NeoplasmsAnimalsCell Line, TumorImidazolesMagnetic Resonance SpectroscopyMiceOximesPyridonesPyrimidinonesTreatment OutcomeBraf protein, mousedabrafenibImidazolesOximesProto-Oncogene Proteins B-rafPyridonesPyrimidinonestrametinib(1)H and (31)P Magnetic Resonance SpectroscopyBRAFMEKMelanomaOptical Redox Imaging

Identifiers

PMID39984334
PMCPMC12758412

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.