P=N/A, N=60, Recruiting, Beijing Chao Yang Hospital

Taken together, NM enhanced the CBP sensitivity of ovarian cancer cells by promoting the ZNF24-mediated inactivation of the WNT2B/Wnt/β-catenin axis. These findings suggest a viable treatment approach for improving CBP resistance in ovarian cancer.

Prostate cancer (PCa) is a multifaceted and therapeutically challenging disease, and functional genomics have helped us develop a better understanding of the mechanisms underlying prostate carcinogenesis, castration-resistant PCa, and metastasis. Keeping in mind the fact that gene fusions have also been discovered in PCa, there has been rapid expansion in the field of molecular oncology and researchers are uncovering new facets regarding the mechanistic regulation of signaling pathways by fusion oncoproteins.

Kidney tubular cells appear not highly susceptible to SARS-CoV-2 infection. Loss of ACE2 into urine in COVID could impact susceptibility and angiotensin metabolism.

Therefore, we have used an original experimental-computational protocol to predict the first resolved structure of the parallel guanine quadruplex secondary structure in the RNA of TMPRSS2, which shows a rigid core flanked by a flexible loop. This represents the first atomic scale structure of the guanine quadruplex structure present in TMPRSS2 messenger RNA.

P1, N=17, Completed, Ensysce Biosciences | Phase classification: P1b --> P1

This study showed a considerable rise in TNF-α and IL-1β serum levels exclusively in COVID-19 patients with TT rs2070788 TMPRSS2 SNP genotype compared to healthy controls. In this study conducted across multiple cities in Iran, no significant association was found between the TMPRSS2 rs2070788 SNP genotypes and COVID-19 severity or mortality.

P=N/A, N=166, Recruiting, Talphera, Inc | Not yet recruiting --> Recruiting | Trial completion date: Aug 2024 --> Dec 2024 | Initiation date: Mar 2024 --> Aug 2024 | Trial primary completion date: Aug 2024 --> Dec 2024

P=N/A, N=100, Recruiting, Wonju Severance Christian Hospital | Enrolling by invitation --> Recruiting | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2025

They inhibited cell-free TMPRSS2 activity like clinical inhibitor of TMPRSS2, Camostat mesylate. Additionally, QUE and TAX exhibited significant inhibition of proliferation and cell cycle accompanied by notable alterations in the morphology of TNBC/PR cells. This study provides valuable insights into potential of QUE and TAX targeting TMPRSS2 overexpressing TNBC.

P3, N=59, Terminated, Institut Pasteur de Dakar | N=186 --> 59 | Recruiting --> Terminated; In conclusion, the results of the SEN-CoV Fadj trial to date do not meet the objectives of the clinical trial and the sample size required to meet them is clearly too large to be achieved within a reasonable time.

Our study found that SWTI caused a significant reduction in the expression of the ACE2 and TMPRSS2 proteins, without any adverse effects on cells. Therefore, our findings suggest that the ACE2 and TMPRSS2 axis can be targeted via SWTI to potentially inhibit SARS-CoV-2 infection.

TMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a potential link between lung cancer and pneumonia caused by SARS-CoV-2 infection.

In addition, suppression of the TLR4/NFκB-p65 pathway with CLI095 significantly reversed the stimulatory effect of LPS on the expression levels of ACE2 and TMPRSS2, whereas TNFα (10 ng/ml) markedly induced the expression levels of ACE2 and TMPRSS2. In conclusion, the present study suggested that dandelion root extracts and TS could be used as prevention strategies for reversing bacteria-driven colorectal cancer cell viability.

Finally, we determined the rTMPRSS2_SP stability for long-term storage. Altogether, our results represent the first comprehensive characterization of TMPRSS2's biochemical properties, providing valuable insights into its serine protease domain.

Bioinformatic analysis of the array outcomes indicated that the protective effect of NSAIDs was associated with reduced expression of (a) tumor promoting inflammatory molecules (M-CSF, IL-33, CCL22, CCL12, CX3CL1, CHI3L1, and CD93), (b) growth factors- growth signaling-associated molecules (Chemerin, FGF acidic, Flt-3 ligand, IGFBP-5, and PEDF), and (c) tumor microenvironment/stromal remodeling proteins MMP2 and MMP9. Overall, our findings corroborate the pathological findings that protective effects of NSAIDs in TMPSS2-ERG fusion-driven prostate tumorigenesis are associated with antiproliferative and anti-inflammatory effects and possible modulation of the immune cell enriched microenvironment.

Our findings propose TMPRSS2 as a critical determinant in lapatinib sensitivity, and Artemisia argyi emerges as a potential agent to overcome lapatinib via activating TMPRSS2 in HER2-positive breast cancer. This study not only unravels the molecular mechanisms driving cell death in HER2-positive breast cancer cells induced by Artemisia argyi but also lays the groundwork for developing novel inhibitors to enhance therapy outcomes.

Overall, 5-ERG-mRPs can robustly detect T2E fusion in PC at the individual level, which can be used on any gene measurement platform without specific normalization procedures. Hence, 5-ERG-mRPs may serve as an auxiliary tool for PC patient management.

This study underscores the potential of DL in deducing genetic alterations from routine slides and identifying their underlying morphological features which might harbor prognostic information. Implications: Our study illuminates the potential of deep learning in effectively inferring key prostate cancer genetic alterations from the tissue morphology depicted in routinely available histology slides, offering a cost-effective method that could revolutionize diagnostic strategies in oncology.

P1, N=111, Completed, Ensysce Biosciences | Active, not recruiting --> Completed | Trial completion date: Jul 2023 --> Apr 2023

P2, N=61, Completed, Suzhou Kintor Pharmaceutical Inc, | Recruiting --> Completed

Serum levels of PSA, MALAT1, and TMPRSS2-ETV1 were abnormal in patients with prostate cancer, and the combined detection of these factors provided a reference for assessing disease progression and predicting the prognosis of prostate cancer.

TMPRSS2:ERG fusion positive status is associated with additional other genomic alterations in castrate resistant disease. In addition, CGP reveals significant differences in both targetable GA and markers of immunotherapy response between TMPRSS2:ERG positive and TMPRSS2:ERG negative CRPC. Given the higher levels of TMB and MSI-high status in TMPRSS2:ERG negative CRPC, TMPRSS2:ERG wild type may be a potential biomarker for immunotherapy response.

Patients in part 1 regimen-finding phase received proxalutamide plus specific ETs (letrozole [cohort A], exemestane [cohort B], or fulvestrant [cohort C]) and were assessed for dose-limiting toxicity (DLT), PK, PD, and anti-tumor activity. These findings suggested favorable clinical outcomes and safety profiles of the combination of proxalutamide and fulvestrant in AR+/HR+/HER2- mBC patients who have progressed on the first-line therapy, and maybe with better efficacy in patients with lower AR/ER ratio. Trial registration: NCT20191063

P2/3, N=256, Recruiting, University Hospital Padova | Trial completion date: Dec 2021 --> Dec 2024 | Trial primary completion date: Dec 2021 --> Dec 2024

Furthermore, immunohistochemical analysis of mouse liver, kidney, and lung tissues demonstrated a decrease in ACE2 and TMPRSS2 protein expression levels. Consequently, this article suggests that A. indica and its constituents have the potential to reduce ACE2 and TMPRSS2 protein expression levels, thus aiding in the prevention of SARS-CoV-2 infections.

Notably, there were no moderately differentiated (MD) adenocarcinomas in the dorsolateral prostate of naproxen groups, and its incidence also decreased by ~79-91% in the aspirin cohorts. In contrast, NSAIDs showed little protective effect against prostate tumorigenesis in Hi-Myc mice, suggesting that NSAIDs exert a specific protective effect against TMPRSS2-ERG (fusion)-driven PCa.

Higher frequencies of risk alleles were confirmed in the SNPs, KLK3 rs2735839_A, ELAC2 rs4792311_A, and TMPRSS2 rs12329760_T in patients with Pca. Rs2735839_A was associated with risk of Pca and rs4792311_A with severity and Gleason score of 7(4 + 3) or greater. There is a need for careful observation of rs2735839 and rs4792311 in association with the prostatic biopsy due to the increased risk of Pca.

P4, N=778, Not yet recruiting, Xu Li

The inhibition of p300 has been shown to reduce the proliferation of prostate cancer cells with TMPRSS2:ETS (E26 transformation-specific) fusions, and combining p300 inhibitors with other targeted therapies may increase their efficacy. Overall, the interplay between the p300 and TMPRSS2 pathways is an active area of research.

TMPRSS2-ERG and androgen receptor RNA were detected down to 3x10 and 5x10 copies respectively in under 30 minutes. Administration of these assays onto the ISFET Lab-on-chip device was successful and the specificity of each marker was corroborated with mRNA extracted from prostate cancer cell lines.

Monotherapies were initiated including letrozole (2.5 mg/day on days 1-14) for cohort A, exemestane (25 mg/day on days 1-14) for cohort B, and fulvestrant (intramuscularly 500 mg once on days 1, 15 and 28) for cohort C, followed by proxalutamide 200 mg QD and ETs for in a 28-day cycle. Conclusions This study suggested a good antitumor activity and safety profile of the combination therapy of proxalutamide and fulvestrant for HR+/HER2-/AR+ mBC patients in the ≥2nd-line settings. Moreover, it may provide survival benefits for these patients, warranting further investigation in a larger population.

Proxalutamide exerted similar effects as enzalutamide, an AR antagonist prescribed for advanced prostate cancer, in decreasing AR signaling and expression of TMPRSS2 and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor...Importantly, proxalutamide inhibited infection by multiple SARS-CoV-2 variants and synergized with remdesivir...Mechanistically, we found that proxalutamide increased levels of NRF2, an essential transcription factor that mediates antioxidant responses, and decreased lung inflammation. These data provide compelling evidence that proxalutamide can prevent SARS-CoV-2 infection and cytokine-induced lung damage, suggesting that promising clinical data may emerge from ongoing phase 3 trials.

We tested the performance of FTAS-seq with well-characterized prostate cancer cell lines and utilized the technique for the analysis of patient RNA samples. FTAS-seq chemistry combined with appropriate primer panels holds great potential as a tool for biomarker discovery that can support the development of personalized cancer therapies.

The highest predictive potential was found with the EEF1A1P5, RPLP0P6, ZNF483, CIBAR1, HECTD2, OGN, and CLIC4 genes. We also reviewed the main transcriptome changes in the groups at intermediate risk of PCa-Gleason Score 7 (groups 2 and 3 according to the ISUP classification)-on the basis of which the LPL, MYC, and TWIST1 genes were identified as promising additional prognostic markers, the statistical significance of which was confirmed using qPCR validation.

The expression levels of TMPRSS2 were found to correlate with nuclear AhR expression and with cancer stage in lung cancer patient tissue. Long-term exposure to PM2.5 could promote tumor progression in lung cancer through activation of EGFR and AhR to enhance the TMPRSS2-IL18 pathway.

Camostat and nafamostat (co-crystal) were utilized as reference ligands against TMPRSS2, whereas mefloquine was used as a reference ligand against spike protein. Furthermore, slight variances in the MD simulation demonstrated consistent binding to TMPRSS2 and spike protein after the initial 50 ns. These results are highly valuable in the search for a treatment for SARS-CoV-2 infection.

PCA3 score detected in urine demonstrated moderate sensitivity and good specificity in differentiation between PCa and non-PCa and high sensitivity and specificity in differentiation between clinically significant PCa and non-PCa.

The synonym SNP rs11554137 IDH1 was found in tumor tissue but not in the normal tissue in one case. A larger cohort of Colombian PCa patients is needed for future studies to validate these findings and gain a better understanding of the molecular profile of this cancer in our population and if there are any differences by Colombian regions.

Commonly found mutations include L702H, W742C, H875Y, F877L and T878A, while the F877L mutation can convert second-generation antagonists such as enzalutamide and apalutamide into agonists. However, pruxelutamide, another second-generation AR antagonist, has no agonist activity with the F877L and F877L/T878A mutants and instead maintains its inhibitory activity against them...Additional structural studies suggest that both the L702H and F877L mutations are important for conformational changes. This structural variability in the AR LBD could affect ligand binding as well as the resistance to antagonists.

All these may imply that TMPRSS2 might be a novel prognostic biomarker and serve as a potential immunomodulator target of immunotherapy combination therapies in LUAD patients nonresponse to anti-PD-1 therapy. Also, these findings may suggest we should pay more attention to LUAD patients, especially those infected with COVID-19, who should avoid medicating TMPRSS2 inhibitors, such as ginsenosides to gain prophylactic and therapeutic benefits against COVID-19.

Molecular alterations in 3 samples showed a microsatellite-stable disease with low tumor mutation burden and variable PTEN, PTCH1, KDM6A, ARv7, and PIK3CA loss/alteration, TP53 mutation, TMPRSS2-ERG fusion, and MYC, PIK3CB, RICTOR, or IRS2 amplification. Our findings suggest that PGCC is a rare and aggressive subtype of prostate carcinoma whose recognition may steer clinicians to adopt more aggressive treatments and investigate new therapeutic strategies.