# Optogenetics for Investigating and Targeting Hallmark Traits of Cancer

**Authors:** Hannah Kienbacher, Muhammad Hashim, Michael Grusch

PMC · DOI: 10.3390/biom16020217 · Biomolecules · 2026-02-02

## TL;DR

Optogenetics allows precise control of cell functions using light, helping researchers study and target cancer traits in new ways.

## Contribution

A review of optogenetic tools and their applications in cancer research, highlighting their potential for therapeutic and investigative purposes.

## Key findings

- Optogenetics enables precise regulation of ion flux, gene expression, and protein interactions in cancer studies.
- It helps identify critical signaling circuits and potential drug targets in cancer progression.
- Optogenetics improves control in cell-based therapies and aids in drug screening and immune modulation.

## Abstract

The light-mediated, specific, and precise control of cell functions enabled by optogenetics has become a versatile method for investigating and combatting cancer. An increasing set of optogenetic tools enables tightly controlled regulation of ion flux across biological membranes, gene expression, gene editing, and protein–protein interactions and is being used to interrogate hallmark traits of cancer at the cellular, subcellular, and organismic level. This enables, on the one hand, the identification of critical signaling circuits required for cancer development and progression in vitro and in animal models and can flag potential intervention points for pharmacologic interference. On the other hand, optogenetics can improve the level of control in cell-based therapeutics. The current article provides a review of optogenetic tools and approaches used in the cancer research field and their multiple applications for improving our understanding of signal transduction pathways, modulating immune functions in the tumor microenvironment, facilitating drug screening, or directly attacking cancer cells. Key advantages and achievements of optogenetics in the cancer research field and remaining barriers for clinical applications are discussed.

## Linked entities

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

## Full-text entities

- **Genes:** braf (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 403065] {aka sierrabraf}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, TRIM21 (tripartite motif containing 21) [NCBI Gene 6737] {aka RNF81, RO52, Ro/SSA, SSA, SSA1, TRIM21/Ro52}, TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, FGFR1 (fibroblast growth factor receptor 1) [NCBI Gene 2260] {aka BFGFR, CD331, CEK, ECCL, FGFBR, FGFR-1}, TNFSF10 (TNF superfamily member 10) [NCBI Gene 8743] {aka APO2L, Apo-2L, CD253, TANCR, TL2, TNLG6A}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, TNFAIP8 (TNF alpha induced protein 8) [NCBI Gene 25816] {aka GG2-1, MDC-3.13, NDED, SCC-S2, SCCS2}, RAC1 (Rac family small GTPase 1) [NCBI Gene 5879] {aka MIG5, MRD48, Rac-1, TC-25, p21-Rac1}, HEY (hairy ears, Y-linked) [NCBI Gene 100188776], Mlkl (mixed lineage kinase domain-like) [NCBI Gene 74568] {aka 9130019I15Rik}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, Rho (rhodopsin) [NCBI Gene 212541] {aka Noerg1, Opn2, Ops, RP4}, VPS34 (vacuolar protein sorting 34) [NCBI Gene 842344] {aka ATVPS34, F8A5.4, F8A5_4, PHOSPATIDYLINOSITOL 3-KINASE, PHOSPHATIDYLINOSITOL 3-KINASE, PI3K}, ACVR1 (activin A receptor type 1) [NCBI Gene 90] {aka ACTRI, ACVR1A, ACVRLK2, ALK2, FOP, SKR1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, FMNL2 (formin like 2) [NCBI Gene 114793] {aka FHOD2}, NLGN3 (neuroligin 3) [NCBI Gene 54413] {aka HNL3}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CRY2 (cryptochrome 2) [NCBI Gene 839529] {aka AT-PHH1, ATCRY2, CRYPTOCHROME 2 APOPROTEIN, F19P19.14, F19P19_14, FHA}, PKM (pyruvate kinase M1/2) [NCBI Gene 5315] {aka CTHBP, HEL-S-30, OIP3, PK3, PKM2, TCB}, RALA (RAS like proto-oncogene A) [NCBI Gene 5898] {aka HINCONS, RAL}, Opn4 (opsin 4 (melanopsin)) [NCBI Gene 30044] {aka 1110007J02Rik, Gm533}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, ARHGEF2 (Rho/Rac guanine nucleotide exchange factor 2) [NCBI Gene 9181] {aka GEF, GEF-H1, GEFH1, LFP40, Lfc, NEDMHM}, RRBP1 (ribosome binding protein 1) [NCBI Gene 6238] {aka ES/130, ES130, RRp, hES, p180}, raf1a (Raf-1 proto-oncogene, serine/threonine kinase a) [NCBI Gene 30716] {aka c-raf, craf, raf1}, Sting1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 72512] {aka 2610307O08Rik, ERIS, MPYS, Mita, STING, STING-beta}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}, CFL1 (cofilin 1) [NCBI Gene 1072] {aka CFL, HEL-S-15, cofilin}, FOLH1B (folate hydrolase 1B (pseudogene)) [NCBI Gene 219595] {aka FOLH2, FOLHP, PSM, PSMA-LIKE, PSMAL}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, SOS1 (SOS Ras/Rac guanine nucleotide exchange factor 1) [NCBI Gene 6654] {aka GF1, GGF1, GINGF, HGF, NS4, SOS-1}, CDC42 (cell division cycle 42) [NCBI Gene 998] {aka CDC42Hs, G25K, TKS}, MRTFA (myocardin related transcription factor A) [NCBI Gene 57591] {aka BSAC, MAL, MKL, MKL1, MRTF-A}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, Trpv2 (transient receptor potential cation channel, subfamily V, member 2) [NCBI Gene 22368] {aka GRC, OTRPC2, VRL-1, Vrl1}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, Nr1i3 (nuclear receptor subfamily 1, group I, member 3) [NCBI Gene 12355] {aka CAR, CAR-beta, Care2, ESTM32, MB67}, XYLT2 (xylosyltransferase 2) [NCBI Gene 64132] {aka PXYLT2, SOS, XT-II, XT2, xylT-II}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, RALB (RAS like proto-oncogene B) [NCBI Gene 5899], UQCC6 (ubiquinol-cytochrome c reductase complex assembly factor 6) [NCBI Gene 728568] {aka BR, BRAWNIN, C12orf73}, GPC3 (glypican 3) [NCBI Gene 2719] {aka DGSX, GTR2-2, MXR7, OCI-5, SDYS, SGB}, PHYB (phytochrome B) [NCBI Gene 816394] {aka HY3, MSF3.17, MSF3_17, OOP1, OUT OF PHASE 1, PHYTOCHROME B}, RET (ret proto-oncogene) [NCBI Gene 5979] {aka CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, Fadd (Fas associated via death domain) [NCBI Gene 14082] {aka Mort1/FADD}, Gsdmd (gasdermin D) [NCBI Gene 69146] {aka 1810036L03Rik, DF5L, Dfna5l, GsdmD-1, Gsdmdc1, M2-4}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}
- **Diseases:** inflammation (MESH:D007249), injury to (MESH:D014947), metastasis (MESH:D009362), melanoma (MESH:D008545), glioma (MESH:D005910), prostate cancer (MESH:D011471), tumorigenic (MESH:D002471), lung cancer (MESH:D008175), infection (MESH:D007239), Malignancies (MESH:D009369), cytotoxicity (MESH:D064420), metastatic (MESH:D000092182), lymphoma (MESH:D008223), retinoblastoma (MESH:D012175), breast cancer (MESH:D001943), hypoxic (MESH:D002534), uveal melanoma (MESH:C536494), oncogenes (MESH:D000074723), oncogenesis (MESH:D063646), ovarian carcinoma (MESH:D010051), hepatocellular carcinoma (MESH:D006528), hematologic malignancies (MESH:D019337)
- **Chemicals:** pyruvate (MESH:D019289), Ca2+ (-), proton (MESH:D011522), tamoxifen (MESH:D013629), lactic acid (MESH:D019344), ATP (MESH:D000255), cation (MESH:D002412), glucose (MESH:D005947), lanthanide (MESH:D028581), chloride (MESH:D002712), ROS (MESH:D017382), Calcium (MESH:D002118)
- **Species:** Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Escherichia coli (E. coli, species) [taxon 562], Danio rerio (leopard danio, species) [taxon 7955], Pseudomonas aeruginosa (species) [taxon 287], Adenoviridae (family) [taxon 10508], Mus musculus (house mouse, species) [taxon 10090], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Homo sapiens (human, species) [taxon 9606], Xenopus laevis (African clawed frog, species) [taxon 8355], Chlamydomonas reinhardtii (species) [taxon 3055]
- **Mutations:** D156A
- **Cell lines:** HEK293FT — Homo sapiens (Human), Transformed cell line (CVCL_6911), LL/2 — Mus musculus (Mouse), Hybridoma (CVCL_C4DW), MDA-MV-468 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0419), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), LiCAR-T — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_A9P5), MCF7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12937673/full.md

## References

183 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937673/full.md

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Source: https://tomesphere.com/paper/PMC12937673