FOLH1 overexpression

The selective uptake of PSMA-1-Pc413 in these cancer tissues as well as the characterization and validation of PSMA expression on neovasculature in this syngeneic 4T1 model emphasizes their potential for advancements in targeted therapies and imaging techniques for BCa. PSMA holds great promise as an oncogenic target for BCa and its associated metastases.

No abstract available

Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Increased prostatic PSMA uptake on PET might be estimated based on T2 MRI alone. Further investigation with larger cohorts and external validation is needed to assess whether PSMA uptake can be predicted accurately enough to help in the interpretation of mpMRI.

After several years of clinical experience with PSMA tracers, the specificity is satisfactory; however, concerns about the specificity are raising day by day due to the newly laid out nonprostatic malignant and benign lesions with high PSMA expression. Herein, we present an incidental 68Ga-PSMA uptake in an intramuscular granular cell tumor.

The present preclinical and clinical data demonstrate that the combination of EBRT with dose escalation by PSMA-RLT improves tumor control and potentially prolongs survival. This may pave the way for further clinical investigations of this approach to explore the curative potential of the combination therapy.

Interestingly, FOLH1 expression was associated with relapse-free and distant metastasis-free survival in patients with BLBC. The BLBC subtype exhibited frequent amplification and overexpression of PSMA, supporting the exploration of PSMA-targeting radiopharmaceuticals in this aggressive breast cancer subtype.

The patient responded well to this treatment, but recurrence was ultimately inevitable. This case represents a typical example of mixed neuroendocrine prostate carcinoma and highlights its resistant phenotype in response to quadruplet therapy.

Co-upregulation of pSMAD3L(S204) and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis, and pSMAD3L(204) may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.

Our research demonstrated that lnc-PSMA8-1 was activated by GEFT and that the former positively regulated mTOR expression by sponging miR-144-3p to promote the progression of RMS. Therefore, targeting this network may constitute a potential therapeutic approach for the management of RMS.

P2, N=60, Recruiting, Mayo Clinic | Trial completion date: Feb 2024 --> Jul 2025 | Trial primary completion date: Dec 2023 --> Jan 2025

In contrast, PSMA7 knockdown inhibited their proliferation and motility, and significantly suppressed apoptosis. This study analyzed multiple proteins that may play a key role in ESCA progression, and identified the pro-cancer role of PSMA7.

PSMA-targeted therapies are rapidly advancing, but their efficacy is strongly limited by the heterogeneous expression of the target. A thorough comprehension of how PSMA is regulated will help improve the outcomes through increasing PSMA expression and will provide the basis for synergistic combination therapies.

Within a subset of TNBC patients, there is a prevalent overexpression of PSMA, which appears to be linked with improved relapse-free and distant metastasis-free survival. Our study succinctly highlights the significance of PSMA overexpression in TNBC and its potential impact on patient outcomes and provides a clear and concise overview of the study's contributions to breast cancer research.

177Lu-PSMA-617 seems to be a promising efficacious and safe treatment option for patients with synchronous high-volume mHSPC.

This work suggests that the expression of metabolic enzymes determined by IHC on baseline diagnostic prostate biopsies may have value as biomarkers of risk for rapid PC progression. PSMA may be an independent predictor of risk for progression and should be investigated further in systematic studies.

P=N/A, N=30, Not yet recruiting, The First Affiliated Hospital of Guangzhou Medical University

Conclusions [177Lu]Lu-PSMA-617 holds promise as a valuable addition to the treatment armamentarium for de-novo high-volume mHSPC, and may be particularly beneficial for those ineligible/unwilling for standard chemohormonal treatment options. Randomized trials evaluating [177Lu]Lu-PSMA-617 in high-volume mHSPC are now required to validate our results and definitively establish its role in this upfront setting.

P1, N=9, Completed, Peking Union Medical College Hospital | Not yet recruiting --> Completed

This prospective study revealed that F-PSMA-1007 PET/CT SUVmax is correlated with the ISUP GG and IRS, and thereby could be a tool to characterize intraprostatic PCa lesions.

Docetaxel and cabazitaxel are approved treatments for mCRPC patients. Lu-PSMA-617 is approved as a third-line systemic treatment for mCRPC patients with failure to respond to androgen receptor pathway inhibitors and docetaxel therapy...Several clinical studies and clinical trials on PRLT are currently underway. In the future, the results of these trials will be helpful in evolving treatment strategies for prostate cancer patients.

We reported 2 cases with recurrent hemangiopericytoma grade III with high expression of 68Ga-PSMA-11 in PET/CT. Based on the performed examination, one of them received targeted α-therapy with the IV injection of 225Ac-PSMA-617.

Staining of tumor sections showed similar HER2 and PSMA expression across groups. In conclusion, these results give no support for any benefit from co-treatment with anti-HER2 antibody for PSMA-targeted radioligand therapy.

PSMA3-AS1 promoted GC progression by regulating the miR-329-3p/ALDOA axis. PSMA3-AS1 might serve as a promising and effective target for GC treatment.

Our findings revealed a key role for RAB31 in GC metastasis through regulation of exosome secretion.

In prostate adenocarcinoma, SUVmax of the primary tumor in [68Ga]Ga-PSMA PET/CT correlates with immunohistochemical PSMA expression. In addition, high SUVmax is associated with markers of poor prognoses, such as high PSMA expression, PSA value, and Gleason score.

To date, no PSMA radioligand therapy of RCC patient has been reported according to literature. Here, we report our experience treating a patient with metastatic RCC with 177Lu-PSMA I&T radioligand therapy, but unexpected imaging findings with rapid washout of 177Lu-PSMA from the tumor.

[Ga]Ga-PSMA-11 PET/CT has potential value in the diagnosis of thyroid cancer. [Ga]Ga-PSMA-11 PET/CT could screen out patients who may benefit from PSMA targeted radionuclide therapy.

Primary tumor PSMA expression and [F]FDG uptake seem to play a complementary prognostic role in TC. The majority of patients who expressed PSMA recurred. In the intermediate ATA risk class, patients with negative PSMA immunostaining recurred less than patients expressing PSMA. Additionally, although patients with a negative [F]FDG PET/CT had a favourable long-term outcome, PSMA assessment might be useful to timely identify subjects at higher risk of recurrence.

Docking studies of 15, 17, and 19 were carried out to explore their binding mode in the active site of PSMA. Two near-infrared (NIR) probes, 23 (λ = 650 nm) and 24 (λ = 1088 nm), displayed favorable in vivo NIR imaging and successful NIR-II image-guided tumor resection surgery in PSMA-positive tumor-bearing mice, which demonstrated the effectiveness of these new squaramic acid-based inhibitors.

Immunohistochemical PSMA and Ki67 expression in fresh tumor biopsies, may contribute to predict treatment efficacy of PSMA-RLT in mCRPC patients. This needs to be further explored in prospective cohorts.

Finally, all exploration should lead to the preparation of a report that answers the clinician's question. For this, it is recommended to prepare a structured report that includes the PROMISE criteria as well as the classification of the findings according to PSMA-RADS parameters.

Background: LuPARP (NCT03874884) is evaluating the safety and efficacy of olaparib in combination with 177Lu-PSMA-617 in patients (pts) with mCRPC who have progressed on an androgen receptor pathway inhibitors and docetaxel. We observed high rates of total and PSMA+ CTCs in PSMA-expressing mCRPC. Total and PSMA+ CTCs decline with combined olaparib and 177Lu-PSMA-617 treatment. Early declines in total and PSMA+ CTCs including 12w CTC clearance paralleled PSA responses.

P=N/A, N=160, Not yet recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Docetaxel-conjugated mesoporous silica nanomedicines effectively reduced tumor volume in intratumoral administration using a nude mice PC xenograft model. These results are promising, paving the way for a future applicability as a precision intratumoral medicine for PC in humans.

VCaP cells treated with both enzalutamide and trametinib expressed two-fold more PSMA compared to those treated with the individual medications or neither. PCa with high PSMA expression is characterized by relevant differences in biological processes. If corroborated with PSMA-PET avidity, these results could optimize precision PCa care by informing adjunctive molecular testing or treatment paradigms for low or high PSMA expressing tumors.

The serum stability of ARX517 should effectively deliver more payload to target tumor cells, and in multiple CDX and PDX prostate cancer models, ARX517 showed dose-dependent anti-tumor activity in both enzalutamide-sensitive and enzalutamide-resistant models. The strong preclinical data and recent clinical validation of PSMA as a mCRPC target provide rationale for evaluation of ARX517 as a potential prostate cancer treatment. ARX517 is currently in a Phase 1 dose escalation trial (ARX517-2011 [NCT04662580]) in the United States.

P2, N=60, Recruiting, Mayo Clinic | Trial primary completion date: Feb 2023 --> Dec 2023

[Lu]Lu-PSMA-induced apoptosis rates were highest in BT-20 and MDA-MB-231 associated endothelial cells. Together, these findings demonstrate the potential of PSMA-targeted therapy in TNBC.

Furthermore, PSMA1 knockdown significantly decreased the proliferation of LUSC cells and promoted the apoptosis of LUSC cells, and these effects were reversed by PSMA1 overexpression. The results of this project supported that PSMA1 might be a critical gene regulating the development of LUSC and has the potential to be explored as a prognostic biomarker of LUSC.