FOLH1 (Folate hydrolase 1)

Under ultrasound irradiation, the targeted nanobubbles successfully activate autophagy and exert an anti-tumor effect through inducing autophagy-related cell death. The targeted nanobubbles demonstrate specific accumulation in PSMA-positive tumors, dynamic monitoring therapy, and significantly amplified therapeutic efficacy against prostate cancer, bringing a non-invasive, promising approach for prostate cancer therapy.

SH may exert its anti-PCa effects by regulating key biomarkers such as GSTP1 and CXCR2, interfering with oncogenic signalling pathways including Rap1, Ras and MAPK, and modulating the infiltration levels of immune cells such as M0/M1 macrophages simultaneously. The online version contains supplementary material available at 10.1007/s40203-025-00511-5.

Quantitative parameters derived from PSMA PET/CT scans provide additional diagnostic accuracy for detecting extraprostatic tumor extension, particularly for ≥ pT3b-stage disease, outperforming visual assessment (miT-stage) alone.

This case highlights prostate-specific membrane antigen (PSMA) expression associated with cSDH, likely reflecting inflammation-driven neoangiogenesis. Recognition of such uptake is essential to avoid misinterpretation as metastatic disease and may provide novel insights into cSDH pathophysiology and potential therapeutic targets.

In summary, current evidence highlights the need to clarify the role of PSMA PET/CT after RT. A better definition of its diagnostic value is essential to guide treatment decisions and future clinical guideline.

In addition, the in vivo efficacy was also assessed in xenograft mouse models of non-CNS tumors, where PSMA CAR T cell treatment resulted in significant tumor regression and robust accumulation of CAR T cells within the tumor microenvironment. Together, these findings establish PSMA as a promising surface antigen beyond prostate cancer and provide preclinical evidence supporting the development of PSMA-directed therapies for this highly lethal pediatric cancer.

DEHP-THRB showed strongest binding affinity, suggesting direct toxicological interaction. This study characterizes a computationally derived gene signature associated with DEHP toxicity in UCEC, highlighting their prognostic and immunological significance as potential molecular footprints, while acknowledging that direct exposure inference requires future validation with measured biomonitoring data.

Moreover, [ 68 Ga]-Ga-PSMA-DIM maintained relatively high uptake in LNCaP and 22Rv1 tumors even after 3 h (3.84 ± 0.50 %ID/mL and 3.59 ± 0.57 %ID/mL, respectively). In conclusion, [ 68 Ga]-Ga-PSMA-DIM could sensitively and specifically differentiate models with varying PSMA expression levels and show notable retention in vivo.

While EC1169 showed limited activity, CTC and imaging analyses showed significant heterogeneity in PSMA expression on CTCs in patients with predominantly PSMA-positive lesions on SPECT. Our study highlights the importance of assessing both PSMA-based CTC and imaging assays in future validation trials.

Proteomic analysis further demonstrated down-regulation of folate hydrolase 1 (FOLH1), a key enzyme in glutamate metabolism, implicating metabolic dysregulation in TCP pathogenesis. The depletion of arginine and associated metabolic disruptions are associated with ICIs-TCP and may represent a potential therapeutic target for mitigating TCP risk in patients receiving ICIs.

Furthermore, risk models incorporating specific protein signatures effectively stratified patients by platinum sensitivity/resistance (9-protein panel: ILK, CDCP1, CD86, CLDN4, CLEC1B, CDHR5, CLDN11, JAM2, FOLH1), lymph node metastasis status (7-protein panel: APOE, CD28, CLDN4, FOLH1, ITGAL, JAML, ULBP3), and post-surgical residual disease burden (4-protein panel: CD44, CLMP, ITGA4, AMIGO1), with Cluster 13 (ITGB1-high) also significantly associated with residual disease. This work demonstrates the power of single-EV proteomics combined with machine learning for non-invasive diagnosis and clinical outcome assessment in advanced ovarian cancer, though the absence of early-stage patients limits its applicability for early detection.

Available therapeutic options include radioligand therapy (e.g. lutetium-177-PSMA-617), cabazitaxel, PARP inhibitors (particularly for patients with DNA repair gene alterations), second-line ARTAs, further chemotherapy and immunotherapeutic approaches. Finally, the review provides an overview of promising emerging therapies poised to expand the treatment landscape for mCRPC. These include bispecific T cell engagers, androgen receptor degraders, and antibody-drug conjugates, which are currently under investigation in clinical trials and may soon offer new avenues for treatment beyond traditional mechanisms.