Evidence map›Paper›PMID 40347280›Full record

ReviewNaunyn-Schmiedeberg's archives of pharmacology2025

Combination therapies and novel delivery systems: a new frontier in overcoming TRAIL resistance in gastric cancer.

Paul Rodrigues, Abdulrahman T Ahmed, Majid Jabir, Khetam Habeeb Rasool, Soumya V Menon, Aryantika Sharma, M Ravi Kumar, Matheel D Al-Sabti, Sabrean F Jawad, Salah Hassan Zain Al-Abdeen

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In one paragraph

Review in Naunyn-Schmiedeberg's archives of pharmacology, 2025. 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

10 authors.

Paul RodriguesDepartment of Science, King Khalid University, Al-Faraa, Saudi Arabia.
Abdulrahman T AhmedCollege of Nursing, University of Al-Maarif, Al-Anbar, 31001, Iraq. Abdulrahman.dheyab@uoa.edu.iq.
Majid JabirDepartment of Applied Sciences, University of Technology, Baghdad, Iraq. majidjabir.ramadi@gmail.com.
Khetam Habeeb RasoolDepartment of Biology, College of Science, University of Mustansiriyah, Mustansiriyah, Iraq.
Soumya V MenonDepartment of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to Be University), Bangalore, Karnataka, India.
Aryantika SharmaChandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjeri, Mohali, 140307, Punjab, India.
M Ravi KumarDepartment of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra, Pradesh, India.
Matheel D Al-SabtiDepartment of Pharmacy, Al-Hikma University College, Baghdad, Iraq.
Sabrean F JawadDepartment of Pharmacy, Al-Mustaqbal University College, 51001, Hillah, Babylon, Iraq.
Salah Hassan Zain Al-AbdeenDepartment of Medical Laboratories Technology, AL-Nisour University College, Baghdad, Iraq.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gastric cancer (GC) presents a formidable challenge in oncology, mainly due to its inherent resistance to therapies such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This review delineates the multifaceted mechanisms underlying TRAIL resistance in GC, encompassing the deregulation of death receptors (DRs) and decoy receptors (DcRs), aberrant signaling pathways, and the influence of the tumor microenvironment (TME). Innovative strategies such as nanoparticle-based drug delivery systems and oncolytic viral therapies are being explored to counteract these challenges. Nanoparticles enhance TRAIL delivery and efficacy by exploiting the enhanced permeability and retention (EPR) effect, while oncolytic viruses can selectively target cancer cells and stimulate immune responses. Combination therapies, integrating TRAIL with conventional chemotherapeutics like paclitaxel, cisplatin, and 5-fluorouracil, have shown promise in overcoming resistance by modulating apoptotic pathways and downregulating multidrug resistance genes. Additionally, novel agents like cyclopamine, decitabine, and genistein have emerged as effective TRAIL sensitizers by modulating apoptotic pathways and enhancing DR5 expression. Furthermore, the integration of epigenetic modifiers can restore TRAIL sensitivity by demethylating DR4 and DR5 genes. This review emphasizes the need for a comprehensive understanding of the molecular underpinnings of TRAIL resistance and the potential of combination therapies and TRAIL delivery by nanoparticles and oncolytic viruses to enhance treatment outcomes in GC. Future research should focus on elucidating predictive biomarkers and optimizing therapeutic regimens to improve the clinical efficacy of TRAIL-based strategies in GC.

Indexed as

Antineoplastic AgentsDrug Delivery SystemsDrug Resistance, NeoplasmStomach NeoplasmsTNF-Related Apoptosis-Inducing LigandAnimalsCombined Modality TherapyHumansNanoparticlesAntineoplastic AgentsTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanCombination therapyGastric cancerNanoparticlesOncolytic virusesResistanceTRAIL

Identifiers

PMID40347280

What Socratic holds

Textmetadata
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.