# Exercise-derived extracellular vesicles in oncology: a new frontier for translational nanomedicine

**Authors:** Monica Silvestri, Cristina Fantini, Guglielmo Duranti, Elisa Grazioli, Daniela Caporossi, Carolina Balbi, Ivan Dimauro

PMC · DOI: 10.1186/s12967-026-07742-w · 2026-01-28

## TL;DR

Exercise-derived extracellular vesicles may offer new ways to treat cancer and protect the heart during therapy.

## Contribution

The paper introduces exercise-derived extracellular vesicles as a novel area in translational nanomedicine for oncology.

## Key findings

- ExEVs modulate cancer biology and enhance immune surveillance.
- ExEVs show potential as biomarkers and therapeutic agents in oncology.
- Challenges include vesicle heterogeneity and manufacturing complexities.

## Abstract

Exercise-derived extracellular vesicles (ExEVs) have emerged as pivotal mediators of the systemic benefits associated with physical activity (PA). Growing evidence highlights their involvement in modulating cancer biology, enhancing immune surveillance, and alleviating treatment-related toxicity.

Recent preclinical studies have begun to unravel the molecular composition and functional characteristics of ExEVs, suggesting considerable potential as both biomarkers and therapeutic agents in oncology and cardio-oncology. There is also increasing interest in the development of extracellular vesicle-inspired nanotherapeutics, with the goal of replicating the anticancer and cardioprotective benefits observed with PA in patients with cancer. While these approaches show promise, significant translational challenges persist, including heterogeneity among vesicle populations, manufacturing complexities, and unresolved regulatory questions.

To address these barriers, a coordinated strategy is necessary. This should include the establishment of standardized protocols, promotion of interdisciplinary collaboration, and integration with personalized oncology frameworks. Progress in the therapeutic application of ExEVs may ultimately facilitate the development of innovative, low-toxicity interventions for cancer care.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** PPARD (peroxisome proliferator activated receptor delta) [NCBI Gene 5467] {aka FAAR, NR1C2, NUC1, NUCI, NUCII, PPARB}, SOD2 (superoxide dismutase 2) [NCBI Gene 6648] {aka GC1, GClnc1, IPO-B, IPOB, MNSOD, MVCD6}, MAPK9 (mitogen-activated protein kinase 9) [NCBI Gene 5601] {aka JNK-55, JNK2, JNK2A, JNK2ALPHA, JNK2B, JNK2BETA}, HSP90B2P (heat shock protein 90 beta family member 2, pseudogene) [NCBI Gene 7190] {aka GRP94P1, GRP94b, HSP, HSPCP2, TRA1P1, TRAP1}, IL6ST (interleukin 6 cytokine family signal transducer) [NCBI Gene 3572] {aka CD130, CDW130, GP130, HIES4, HIES4A, HIES4B}, LAMP1 (lysosome associated membrane protein 1) [NCBI Gene 3916] {aka CD107a, LAMPA, LGP120}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], SPARC (secreted protein acidic and cysteine rich) [NCBI Gene 6678] {aka BM-40, OI17, ON, ONT}, MIR206 (microRNA 206) [NCBI Gene 406989] {aka MIRN206, miRNA206, mir-206}, OXTR (oxytocin receptor) [NCBI Gene 5021] {aka OT-R, OTR}, Fndc5 (fibronectin type III domain containing 5) [NCBI Gene 384061] {aka 1500001L03Rik, PeP, Pxp}, Hspa1b (heat shock protein family A (Hsp70) member 1B) [NCBI Gene 108348108] {aka HSP70, HSP70-1, HSP70.1, HSP70.2, Hsp70-2, Hsp72}, Pctp (phosphatidylcholine transfer protein) [NCBI Gene 29510] {aka PC-TP, stARD2}, MIR486-1 (microRNA 486-1) [NCBI Gene 619554] {aka MIR486, MIRN486, hsa-mir-486, hsa-mir-486-1, mir-486-1}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, FSD1 (fibronectin type III and SPRY domain containing 1) [NCBI Gene 79187] {aka GLFND, MIR1}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, Mrc1 (mannose receptor, C type 1) [NCBI Gene 17533] {aka CD206, MR}, Ppm1f (protein phosphatase 1F (PP2C domain containing)) [NCBI Gene 68606] {aka 1110021B16Rik, 4933427B07Rik, CaMKPase, Popx2, mKIAA0015}, SERPINF1 (serpin family F member 1) [NCBI Gene 5176] {aka EPC-1, OI12, OI6, PEDF, PIG35}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, Ltb4r2 (leukotriene B4 receptor 2) [NCBI Gene 114098] {aka LTB4-R2}, MIR1225 (microRNA 1225) [NCBI Gene 100188847] {aka MIRN1225}, AGPAT1 (1-acylglycerol-3-phosphate O-acyltransferase 1) [NCBI Gene 10554] {aka 1-AGPAT1, G15, LPAAT-alpha, LPAATA, LPLAT1}, LINC00328 (long intergenic non-protein coding RNA 328) [NCBI Gene 51152] {aka NCRNA00328, NCRNA00328-1, NCRNA00328A}, ATIC (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase) [NCBI Gene 471] {aka AICAR, AICARFT, HEL-S-70p, IMPCHASE, PURH}, Alox5 (arachidonate 5-lipoxygenase) [NCBI Gene 25290] {aka 5-LOX, LOX5A}, Sod3 (superoxide dismutase 3, extracellular) [NCBI Gene 20657] {aka EC-SOD}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Cyp4b1 (cytochrome P450, family 4, subfamily b, polypeptide 1) [NCBI Gene 24307], Oxtr (oxytocin receptor) [NCBI Gene 25342] {aka OT-R, OTR, OTR1}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, ZBTB1 (zinc finger and BTB domain containing 1) [NCBI Gene 22890] {aka ZNF909}, Notum (NOTUM, palmitoleoyl-protein carboxylesterase) [NCBI Gene 303743] {aka RGD1307119}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, Casp9 (caspase 9) [NCBI Gene 12371] {aka APAF-3, CASP-9, Caspase-9, ICE-LAP6, Mch6}, Nampt (nicotinamide phosphoribosyltransferase) [NCBI Gene 59027] {aka 1110035O14Rik, NAmPRTase, Pbef, Pbef1, Visfatin}, LILRB1 (leukocyte immunoglobulin like receptor B1) [NCBI Gene 10859] {aka CD85J, ILT-2, ILT2, LIR-1, LIR1, MIR-7}, MIR142 (microRNA 142) [NCBI Gene 406934] {aka MIRN142, mir-142}, HSPA5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 3309] {aka BIP, GRP78, HEL-S-89n}, NUSAP1 (nucleolar and spindle associated protein 1) [NCBI Gene 51203] {aka ANKT, BM037, LNP, NUSAP, PRO0310p1, Q0310}, MIR221 (microRNA 221) [NCBI Gene 407006] {aka MIRN221, miRNA221, mir-221}, MIR149 (microRNA 149) [NCBI Gene 406941] {aka MIRN149, mir-149}, DNAJB5 (DnaJ heat shock protein family (Hsp40) member B5) [NCBI Gene 25822] {aka Hsc40}, MIR150 (microRNA 150) [NCBI Gene 406942] {aka MIRN150, miRNA150, mir-150}, Kras (KRAS proto-oncogene, GTPase) [NCBI Gene 24525] {aka K-ras, Kras2, c-Ki-ras, p21}, FNDC5 (fibronectin type III domain containing 5) [NCBI Gene 252995] {aka FRCP2, irisin}, Hspa5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 25617] {aka BIP, GRP 78, GRP78}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, Hspd1 (heat shock protein 1 (chaperonin)) [NCBI Gene 15510] {aka 60kDa, CPN60, HSP-60, HSP-65, Hsp60}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, MIR124-1 (microRNA 124-1) [NCBI Gene 406907] {aka MIR124A, MIR124A1, MIRN124-1, MIRN124A1, mir-124-1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CAT (catalase) [NCBI Gene 847], FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], Mapk9 (mitogen-activated protein kinase 9) [NCBI Gene 26420] {aka JNK2, Prkm9, p54aSAPK}, CYP4B1 (cytochrome P450 family 4 subfamily B member 1) [NCBI Gene 1580] {aka CYPIVB1, P-450HP}, Sgca (sarcoglycan, alpha (dystrophin-associated glycoprotein)) [NCBI Gene 20391] {aka 50DAG, Asg}, MIR23A (microRNA 23a) [NCBI Gene 407010] {aka MIRN23A, hsa-mir-23a, miRNA23A, mir-23a}
- **Diseases:** metabolic dysfunction (MESH:D008659), cardiotoxicity (MESH:D066126), hypoxia (MESH:D000860), NSCLC (MESH:D002289), obesity (MESH:D009765), fatty liver disease (MESH:D005234), cardiovascular strain (MESH:D013180), stroke (MESH:D020521), Cancer (MESH:D009369), endothelial dysfunction (MESH:D014652), lung cancer (MESH:D008175), melanoma (MESH:D008545), PCa (MESH:D011471), inflammation (MESH:D007249), mitochondrial dysfunction (MESH:D028361), pancreatic cancer (MESH:D010190), PC (MESH:D015324), PA (MESH:D059445), oncological (MESH:D000072716), glioblastoma (MESH:D005909), TNBC (MESH:D064726), breast and colon cancer (MESH:D001943), adiposity (MESH:D018205), infarct (MESH:D007238), ovarian and pancreatic cancer (MESH:D010051), cardiac injury (MESH:D006331), hepatic injury (MESH:D056486), ischemic injury (MESH:D017202), hypertrophy (MESH:D006984), cardiovascular disease (MESH:D002318), cytotoxicity (MESH:D064420), reperfusion injury (MESH:D015427), thrombosis (MESH:D013927), lung metastases (MESH:D009362), atherosclerosis (MESH:D050197), colon cancer (MESH:D015179)
- **Chemicals:** GW1516 (MESH:C425931), phospholipid (MESH:D010743), DEX (MESH:D003915), Paclitaxel (MESH:D017239), PAs (MESH:D011478), dinaciclib (MESH:C553669), Anthracycline (MESH:D018943), sphingolipids (MESH:D013107), ROS (MESH:D017382), glucose (MESH:D005947), Lipid (MESH:D008055), Cysteine (MESH:D003545), 5-Aminoimidazole-4-carboxamide ribonucleotide (MESH:C031143), fatty acid (MESH:D005227), phosphatidylserine (MESH:D010718), DXO (-), Dox (MESH:D004317)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** G12D
- **Cell lines:** EO771 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_GR23), HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), N2a — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_0470), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12924560/full.md

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Source: https://tomesphere.com/paper/PMC12924560