Ask about this productRelated genes to: PYGO2 antibody
- Gene:
- PYGO2 NIH gene
- Name:
- pygopus family PHD finger 2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-11-10
- Date modifiied:
- 2016-10-05
Related products to: PYGO2 antibody
Related articles to: PYGO2 antibody
- Despite the success of immunotherapy in other malignancies, castration-resistant prostate cancer (CRPC) remains a formidable challenge due to its immunosuppressive "cold" tumor microenvironment. This environment is characterized by low tumor mutational burden, sparse T-cell infiltration, and the dominance of immunosuppressive factors. This review aims to systematically examine recent advances, current challenges, and future directions in immunotherapy for CRPC, offering novel therapeutic perspectives for this lethal disease with currently limited treatment options. - Source: PubMed
Publication date: 2026/07/15
Xu ZedongXia ZiweiLi JiaxuanYuan SiyingZhao LichunWang Xueni - Chromosome 1q21 copy number alterations (1q21+) are among the most frequent secondary events in multiple myeloma (MM), correlating with poor prognosis and therapy resistance. However, the molecular drivers of this lesion remain poorly defined. Here, we identify PYGO2, a Wnt/β-catenin co-activator located on 1q21, as a critical effector of MM progression. Analysis of primary CD138 plasma cells and public datasets revealed that PYGO2 expression is significantly increased in 1q21+ patients and correlates with chromosome 1q copy number. High PYGO2 levels were associated with adverse cytogenetics and shorter progression-free and overall survival. Functional studies showed that PYGO2 knockdown (KD) in 1q21+ cell lines impaired proliferation, induced cell cycle perturbation coupled with CCND1 downregulation and reduced H3K4me3 enrichment, while increasing Carfilzomib and Bortezomib sensitivity. Conversely, PYGO2 overexpression enhanced cell growth and proteasome inhibitor resistance. RNA-seq profiling of KD cells revealed coordinated suppression of canonical Wnt/TCF target genes involved in proliferation and reshaped the replication stress and DNA damage response transcriptome, suggesting enhanced replication stress. RNA-seq profiling of KD cells also revealed suppression of oncogenic and immunomodulatory pathways, suggesting a broader role in tumor-microenvironment crosstalk. Overall, our data establish PYGO2 as a previously unrecognized effector of 1q21-driven aggressiveness in MM and suggest that it represents a therapeutic vulnerability in high-risk 1q21+ MM patients. - Source: PubMed
Publication date: 2026/07/11
Iannozzi Nicolas ThomasStorti PaolaVescovini RosannaSitzia CamillaPoletti AndreaFranceschi ValentinaTodaro GiannalisaSammarelli GabriellaToscani DeniseRaimondi VincenzoDessena MattiaLungu OxanaMohammadi FazelScita MatteoBernardi MatiaDalla Palma Anna BenedettaRicci StefaniaLorusso BrunoLagrasta Costanza Anna MariaQuaini FedericoAgnelli LucaDonofrio GaetanoGiuliani Nicola - Prostate cancer frequently progresses to lethal, drug-resistant castration-resistant prostate cancer (CRPC), where conventional therapies often fail due to intrinsic and acquired resistance mechanisms. This resistance creates a critical therapeutic impasse, leaving patients with limited options and poor prognoses. Immunotherapy has emerged as a promising strategy to harness the immune system against these treatment-refractory tumors, offering a potential avenue to overcome the immunosuppressive barriers that underlie CRPC drug resistance. This review synthesizes findings from a structured search of PubMed, Web of Science, and Embase (2020-2025), revealing significant clinical progress: 4 vaccine trials, 5 immune checkpoint inhibitor trials, 18 combination therapy trials (≥2 agents), and 6 targeted drug trials have been conducted. Preliminary efficacy was observed in novel approaches like bispecific antibodies (e.g., Xaluritamig achieving 59% PSA50 response), PSMA-CAR-T (P-PSMA-101), and oncolytic viruses (Ad5 PSA/MUC-1/brachyury). Basic research identified four targeted resistance mechanisms (e.g., AR-LLT1, Pygo2, and HnRNP L) and one nanoparticle-mediated triple-combination therapy (CM-AMS@AD NPs integrating photothermal, chemotherapy, and immunotherapy), which enhanced cytotoxic T-cell infiltration and suppressed CRPC growth preclinically. These collective findings suggest the potential of immunotherapy for CRPC in overcoming resistance barriers and improving patient outcomes, with bispecific T cell engagers (Xaluritamig, 59% PSA50) and PSMA-directed CAR-T therapy (P-PSMA-101, >50% PSA reduction) emerging as the most promising near-term candidates and biomarker-stratified combinations (nivolumab plus rucaparib, 84.6% PSA50, in HRR-deficient patients) illustrating the transformative power of precision patient selection; however, these findings require validation in larger, biomarker-stratified trials before definitive conclusions can be drawn. Translating this potential into clinical reality requires optimized patient selection through predictive biomarkers and rigorously validated Phase III trials to confirm durable clinical responses and long-term survival benefits. - Source: PubMed
Publication date: 2026/03/05
Xia XuantaoXia ZiweiYu Lili - Kidney fibrosis, also known as renal fibrosis, is a condition wherein excessive scarring and interstitial inflammation of kidney tissues produce elevated levels of reactive oxygen species (ROS) and Human Pygopus 2 (Pygo2) contributing to disease progression and severity. To prevent these conditions, a fibrotic kidney-microenvironment-responsive hydrogel (PD(diSe)/shPygo2 Hydrogel) platform is designed and fabricated for providing therapy and protecting renal function. The therapeutic hydrogel provided the necessary ROS-responsiveness via cleavage of the diselenide bonds in the presence of elevated oxidative stress promoting changes in the chemo-physical property (adhesiveness, mechanical property, and electronic resistance) of the hydrogel. This transitioned the hydrogel into a more elastic state owing to a shift in Michael addition reaction between the surface amine groups in the PD(diSe) and the oxidized quinone moieties in the matrix facilitating the monitoring process. Moreover, in the presence of ROS-induced 293T cells, the hydrogel exhibited differential electrical resistance and fluorescence compared with the 293T cells alone. Additionally, the presence of shPygo2 provides therapeutic protection to fibrotic scarring and renal function in unilateral ureteral obstruction (UUO) and adenine diet murine models by downregulating the Pygo2 and α-SMA secretion levels, along with promoting ROS scavenging through diselenide bond cleavage. - Source: PubMed
Publication date: 2026/01/19
Jo HayeonRoy KaustuvJeon SeunghoJin Eun-JungPark Sung Young - In hepatocellular carcinoma (HCC), numerous signaling pathways become aberrantly regulated, resulting in sustained cellular proliferation and enhanced metastatic potential. Tumors that lack PYGO2 may not show the same types of tissue remodeling or regenerative features driven by the Wnt/β-catenin pathway, which could make the tumor behave differently from others that are Wnt-positive. PIK3CA-positive tumors are often associated with worse prognosis due to the aggressive nature of the PI3K/AKT pathway activation. This is linked to higher chances of metastasis, recurrence, and resistance to therapies that do not target this pathway. In this paper we present a rare case of hepatocellular carcinoma with PIK3CA-positive and PYGO2-negative signaling pathways, several key aspects of the tumor's behavior, prognosis, and treatment options. Although alpha-fetoprotein (AFP) levels were significantly elevated, the CT and MRI examination showed characteristics of malignancy, HCC with secondary hepatic lesions and associated perfusion disturbances. The case particularities and immunohistochemistry features are highlighted in the context of literature review, the PIK3CA mutation suggesting the activation of the PI3K/AKT/mTOR pathway, a critical signaling pathway involved in cell survival, proliferation, and metabolism. Due to the aggressive nature of PIK3CA mutations, close monitoring and consideration of immunotherapy and targeted treatments are of crucial importance. - Source: PubMed
Publication date: 2025/10/03
Hasan Alexandru MadalinPaul Ioana LarisaCavalu SimonaPop Ovidiu LaureanPaduraru LorenaMagyar IoanChirila Mihaela Doina