Evidence map›Paper›PMID 42439655›Full record

ArticleCells2026

IVMT-Rx-3 Microemulsion as Low-Dose Metronomic Chemotherapy for Melanoma Metastasis.

Rudra Pangeni, Padmanabhan Mannangatti, Ehsan Kaffash, Madeline Gunawardena, Nitai D Mukhopadhyay, Mark C Mochel, Swadesh K Das, Qingguo Xu, Paul B Fisher

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Rudra PangeniDepartment of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Padmanabhan MannangattiVCU Institute of Molecular Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Ehsan KaffashDepartment of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-1903-6690
Madeline GunawardenaDepartment of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0009-0007-9279-0896
Nitai D MukhopadhyayDepartment of Biostatistics, School of Public Health, Virginia Commonwealth University, Richmond, VA 23298, USA.
Mark C MochelDepartment of Pathology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Swadesh K DasVCU Institute of Molecular Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Qingguo XuDepartment of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0003-3191-0771
Paul B FisherVCU Institute of Molecular Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Renato Martins · 1985 to 2026
$51.0M
Modulating growth, progression and metastasis in breast cancer by inhibiting MDA-9R01CA280194 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Swadesh K Das, PAUL B FISHER · 2024 to 2026
$3.1M
Novel Targeted Combinatorial Therapy for Hepatocellular CarcinomaR01CA244993 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B, SARKAR, DEVANAND · 2020 to 2024
$2.7M
Interplay between tumor and microenvironment in bone metastasisR01CA259599 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B, WANG, XIANG-YANG SHAWN · 2021 to 2025
$2.3M
NCI NIH HHS P30 CA016059NCI NIH HHS R01 CA244993NCI NIH HHS R01 CA259599NCI NIH HHS R01 CA280194
6 · The paper itself

Abstract

The pro-metastatic gene MDA-9/Syntenin-1 and its tandem PDZ domains (PDZ1 and PDZ2) provide established targets for intervening in tumor progression and metastasis. Recently, we generated and validated MDA-9/Syntenin-1 antagonists targeting a single PDZ domain (PDZ1i) or both PDZ domains (IVMT-Rx-3) in carcinomas and melanoma. Data reveal that IVMT-Rx-3 possesses immunomodulatory and anti-angiogenic properties, in addition to its well-established anti-invasive capabilities. Despite its significant druggable properties, it cannot be delivered orally, limiting its clinical potential. Here, we characterized an oral microemulsion (ME) formulation of IVMT-Rx-3, IVMT-Rx-3-ME to enhance intestinal permeability, bioavailability, and therapeutic efficacy. Physicochemical analyses demonstrated that the optimized formulation produced a stable IVMT-Rx-3-ME with high drug content (>90%). In vitro permeability and dissolution assays confirmed improved membrane transport and solubility compared with the free drug dispersion control. Pharmacokinetic studies in rats revealed that the ME enabled rapid absorption and sustained systemic exposure, whereas the free drug showed negligible bioavailability. In murine metastatic melanoma models, oral IVMT-Rx-3-ME suppressed tumor growth and lung metastases, and when combined with anti-PD-L1 antibody, produced synergistic antitumor effects with minimal toxicity. Collectively, these findings highlight IVMT-Rx-3-ME as a potent and viable oral metronomic chemotherapy platform for metastatic melanoma, with enhanced combinatorial translational potential with immunotherapies.

Indexed as

Antineoplastic AgentsMelanomaAdministration, MetronomicAdministration, OralAnimalsBiological AvailabilityCell Line, TumorEmulsionsFemaleHumansMaleMiceNeoplasm MetastasisRatsAntineoplastic AgentsEmulsionsbioavailabilityMDA-9/Synteninmelanomametastasisoral formulationPD-L1

Identifiers

PMID42439655
PMCPMC13359644

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.