@article{MTMT:33754849,
	title = {Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors},
	url = {https://m2.mtmt.hu/api/publication/33754849},
	author = {Kovács, Szonja Anna and Fekete, János Tibor and Győrffy, Balázs},
	doi = {10.1038/s41401-023-01079-6},
	journal-iso = {ACTA PHARMACOL SIN},
	journal = {ACTA PHARMACOLOGICA SINICA},
	volume = {44},
	unique-id = {33754849},
	issn = {1671-4083},
	abstract = {Immune-checkpoint inhibitors show promising effects in the treatment of multiple tumor types. Biomarkers are biological indicators used to select patients for a systemic anticancer treatment, but there are only a few clinically useful biomarkers such as PD-L1 expression and tumor mutational burden, which can be used to predict immunotherapy response. In this study, we established a database consisting of both gene expression and clinical data to identify biomarkers of response to anti-PD-1, anti-PD-L1, and anti-CTLA-4 immunotherapies. A GEO screening was executed to identify datasets with simultaneously available clinical response and transcriptomic data regardless of cancer type. The screening was restricted to the studies involving administration of anti-PD-1 (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab) or anti-CTLA-4 (ipilimumab) agents. Receiver operating characteristic (ROC) analysis and Mann-Whitney test were executed across all genes to identify features related to therapy response. The database consisted of 1434 tumor tissue samples from 19 datasets with esophageal, gastric, head and neck, lung, and urothelial cancers, plus melanoma. The strongest druggable gene candidates linked to anti-PD-1 resistance were SPIN1 (AUC = 0.682, P  = 9.1E-12), SRC (AUC = 0.667, P  = 5.9E-10), SETD7 (AUC = 0.663, P  = 1.0E-09), FGFR3 (AUC = 0.657, P  = 3.7E-09), YAP1 (AUC = 0.655, P  = 6.0E-09), TEAD3 (AUC = 0.649, P  = 4.1E-08) and BCL2 (AUC = 0.634, P  = 9.7E-08). In the anti-CTLA-4 treatment cohort, BLCAP (AUC = 0.735, P  = 2.1E-06) was the most promising gene candidate. No therapeutically relevant target was found to be predictive in the anti-PD-L1 cohort. In the anti-PD-1 group, we were able to confirm the significant correlation with survival for the mismatch-repair genes MLH1 and MSH6 . A web platform for further analysis and validation of new biomarker candidates was set up and available at https://www.rocplot.com/immune . In summary, a database and a web platform were established to investigate biomarkers of immunotherapy response in a large cohort of solid tumor samples. Our results could help to identify new patient cohorts eligible for immunotherapy.},
	year = {2023},
	eissn = {1745-7254},
	pages = {1879-1889},
	orcid-numbers = {Fekete, János Tibor/0000-0002-6672-6563; Győrffy, Balázs/0000-0002-5772-3766}
}

@article{MTMT:31822186,
	title = {Anti-cancer strategies targeting the autotaxin-lysophosphatidic acid receptor axis: is there a path forward?},
	url = {https://m2.mtmt.hu/api/publication/31822186},
	author = {Tigyi, Gabor and Dacheux, Mélanie A. and Lin, Kuan-Hung and Yue, Junming and Norman, Derek and Benyó, Zoltán and Lee, Sue Chin},
	doi = {10.1007/s10555-021-09955-5},
	journal-iso = {CANCER METAST REV},
	journal = {CANCER AND METASTASIS REVIEWS},
	volume = {40},
	unique-id = {31822186},
	issn = {0167-7659},
	year = {2021},
	eissn = {1573-7233},
	pages = {3-5},
	orcid-numbers = {Tigyi, Gabor/0000-0001-5371-171X; Benyó, Zoltán/0000-0001-6015-0359}
}

@article{MTMT:30515673,
	title = {Role of autotaxin in cancer stem cells},
	url = {https://m2.mtmt.hu/api/publication/30515673},
	author = {Lee, Dongjun and Suh, Dong-Soo and Lee, Sue Chin and Tigyi, Gabor and Kim, Jae Ho},
	doi = {10.1007/s10555-018-9745-x},
	journal-iso = {CANCER METAST REV},
	journal = {CANCER AND METASTASIS REVIEWS},
	volume = {37},
	unique-id = {30515673},
	issn = {0167-7659},
	abstract = {Stem cells are a rare subpopulation defined by the potential to self-renew and differentiate into specific cell types. A population of stem-like cells has been reported to possess the ability of self-renewal, invasion, metastasis, and engraftment of distant tissues. This unique cell subpopulation has been designated as cancer stem cells (CSC). CSC were first identified in leukemia, and the contributions of CSC to cancer progression have been reported in many different types of cancers. The cancer stem cell hypothesis attempts to explain tumor cell heterogeneity based on the existence of stem cell-like cells within solid tumors. The elimination of CSC is challenging for most human cancer types due to their heightened genetic instability and increased drug resistance. To combat these inherent abilities of CSC, multi-pronged strategies aimed at multiple aspects of CSC biology are increasingly being recognized as essential for a cure. One of the most challenging aspects of cancer biology is overcoming the chemotherapeutic resistance in CSC. Here, we provide an overview of autotaxin (ATX), lysophosphatidic acid (LPA), and their signaling pathways in CSC. Increasing evidence supports the role of ATX and LPA in cancer progression, metastasis, and therapeutic resistance. Several studies have demonstrated the ATX-LPA axis signaling in different cancers. This lipid mediator regulatory system is a novel potential therapeutic target in CSC. In this review, we summarize the evidence linking ATX-LPA signaling to CSC and its impact on cancer progression and metastasis. We also provide evidence for the efficacy of cancer therapy involving the pharmacological inhibition of this signaling pathway.},
	keywords = {Lysophosphatidic acid; Cancer stem cells; AUTOTAXIN; lysophosphatidic acid receptor},
	year = {2018},
	eissn = {1573-7233},
	pages = {509-518},
	orcid-numbers = {Tigyi, Gabor/0000-0001-5371-171X}
}

@article{MTMT:2756703,
	title = {Controlling cancer through the autotaxin-lysophosphatidic acid receptor axis.},
	url = {https://m2.mtmt.hu/api/publication/2756703},
	author = {Gotoh, M and Fujiwara, Y and Yue, J and Liu, J and Lee, S and Fells, J and Uchiyama, A and Murakami-Murofushi, K and Kennel, S and Wall, J and Patil, R and Gupte, R and Balazs, L and Miller, DD and Tigyi, Gabor},
	doi = {10.1042/BST20110608},
	journal-iso = {BIOCHEM SOC T},
	journal = {BIOCHEMICAL SOCIETY TRANSACTIONS},
	volume = {40},
	unique-id = {2756703},
	issn = {0300-5127},
	abstract = {LPA (lysophosphatidic acid, 1-acyl-2-hydroxy-sn-glycero-3-phosphate), is a growth factor-like lipid mediator that regulates many cellular functions, many of which are unique to malignantly transformed cells. The simple chemical structure of LPA and its profound effects in cancer cells has attracted the attention of the cancer therapeutics field and drives the development of therapeutics based on the LPA scaffold. In biological fluids, LPA is generated by ATX (autotaxin), a lysophospholipase D that cleaves the choline/serine headgroup from lysophosphatidylcholine and lysophosphatidylserine to generate LPA. In the present article, we review some of the key findings that make the ATX-LPA signalling axis an emerging target for cancer therapy.},
	keywords = {Animals; Humans; signal transduction; Neoplasm Invasiveness; Xenograft Model Antitumor Assays; Lysophospholipids/metabolism; Molecular targeted therapy; Antineoplastic Agents/pharmacology/therapeutic use; Receptors, Lysophosphatidic Acid/*metabolism; Phosphodiesterase Inhibitors/pharmacology/therapeutic use; Phosphoric Diester Hydrolases/genetics/*metabolism/secretion; Organophosphonates/pharmacology/therapeutic use; Neoplasms/drug therapy/*metabolism/pathology/secretion},
	year = {2012},
	eissn = {1470-8752},
	pages = {31-36},
	orcid-numbers = {Tigyi, Gabor/0000-0001-5371-171X}
}

@article{MTMT:2756712,
	title = {Aiming drug discovery at lysophosphatidic acid targets.},
	url = {https://m2.mtmt.hu/api/publication/2756712},
	author = {Tigyi, Gabor},
	doi = {10.1111/j.1476-5381.2010.00815.x},
	journal-iso = {BR J PHARMACOL},
	journal = {BRITISH JOURNAL OF PHARMACOLOGY},
	volume = {161},
	unique-id = {2756712},
	issn = {0007-1188},
	abstract = {Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is the prototype member of a family of lipid mediators and second messengers. LPA and its naturally occurring analogues interact with G protein-coupled receptors on the cell surface and a nuclear hormone receptor within the cell. In addition, there are several enzymes that utilize LPA as a substrate or generate it as a product and are under its regulatory control. LPA is present in biological fluids, and attempts have been made to link changes in its concentration and molecular composition to specific disease conditions. Through their many targets, members of the LPA family regulate cell survival, apoptosis, motility, shape, differentiation, gene transcription, malignant transformation and more. The present review depicts arbitrary aspects of the physiological and pathophysiological actions of LPA and attempts to link them with select targets. Many of us are now convinced that therapies targeting LPA biosynthesis and signalling are feasible for the treatment of devastating human diseases such as cancer, fibrosis and degenerative conditions. However, successful targeting of the pathways associated with this pleiotropic lipid will depend on the future development of as yet undeveloped pharmacons.},
	keywords = {Animals; Humans; LIGANDS; *Drug Discovery; Receptors, G-Protein-Coupled/*agonists/*antagonists & inhibitors/physiology; Lysophospholipids/*metabolism/physiology},
	year = {2010},
	eissn = {1476-5381},
	pages = {241-270},
	orcid-numbers = {Tigyi, Gabor/0000-0001-5371-171X}
}