VPS34 in Autophagy, Cancer and Cancer Therapy
Open accessAbstract
Autophagy is a fundamental lysosome-dependent degradation process, which maintains cellular homeostasis in response to stress. VSP34 (Vacuolar Protein Sorting 34, PIK3C3), as the only Class III phosphatidylinositol 3-kinase, generates phosphatidylinositol 3-phosphate (PI3P) for au-to-phagosome nucleation and maturation, thereby providing a critical adaptive survival pathway for cells experiencing metabolic stress. The VPS34-autophagy axis displays a context-dependent dual roles in cancer: it can restrain early tumorigenesis; however, in established tumors it can promote survival under hypoxia, nutrient deprivation, and therapeutic pressure. Additionally, VPS34 shapes the tumor microenvironment (TME) by influencing both immune and cancer cells through modulating autophagy, cGAS-STING (cyclic GMP-AMP synthase Stimulator of Interfer-on Genes) and STAT1 pathways. VPS34 inhibition has been reported to induce interferon response that enhance CD8+ T and natural killer (NK) cell infiltration and convert cold tumor into hot, providing a rationale for combination of VPS34 inhibitors with cancer immunotherapies. In this review, we summarize the molecular functions and regulations of VPS34 in autophagy and dis-cuss recent advances linking VPS34 to tumor and cancer immunotherapy.
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The PI3K/AKT/mTOR pathway is a major downstream signaling cascade of EGFR and represents an important bypass mechanism contributing to resistance to cetuximab and panitumumab.
“The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is a major downstream signaling cascade of EGFR and represents an important bypass mechanism contributing to resistance to cetuximab and panitumumab [40,41,42,43,44].”
From Overcoming Resistance to Anti-EGFR Therapies: Mechanisms of Cetuximab and Panitumumab Resistance and Emerging Combination Strategies (2026) · cites this paper as [43]
The Introduction describes PI3K classes, and §7.2 discusses VPS34 inhibitors and resistance to other therapies. Neither passage addresses PI3K/AKT/mTOR as an EGFR downstream pathway or a bypass mechanism for resistance to cetuximab or panitumumab. Searches for those drugs and for EGFR downstream bypass signaling found no supporting passage in our copy. (LLM, conf=0.74)
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Flagged first, then by citations
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Cited by
Sorted by citations
Henrykowska, G., Bartusik-Aebisher, D., Dynarowicz, K., Ramesh, T. S., Smolak, B., & Aebisher, D. (2026) · Pharmaceuticals · doi:10.3390/ph19071041 · Cited by 1 · see citing works
- Authors
- Bartolini, E., Janji, B., & Gao, R.
- Affiliations
- University of Luxembourg (LU)
- Luxembourg Institute of Health (LU)
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2026-03-04
- Volume
- 15
- Issue
- 7
- Pages
- 636-636
- ISSN
- 2073-4409 (ISSN-L)
- OpenAlex
- W7148428204
- Cited by
- 1
- References
- 140
- Citations by year
- 2026: 1
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cells (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondation du Pélican de Mie et Pierre Hippert-Faber
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- Vps34, PIK3C3, autophagy, class III phosphatidylinositol 3-kinase, phosphatidylinositol 3-phosphate, tumor microenvironment, cancer immunotherapy, cGAS-STING pathway, STAT1, interferon response, cold tumor conversion, tumor hypoxia, nutrient deprivation, CD8+ T cell infiltration, natural killer cells
- MeSH terms
- cGAS-STING Signaling Pathway, Animals, Autophagy, Humans, Neoplasms, Class III Phosphatidylinositol 3-Kinases, Tumor Microenvironment
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