We have developed VT1021 that induces the expression of thrombospondin-1 (TSP-1) in myeloid-derived suppressor cells (MDSCs) recruited to the tumor microenvironment (TME). Our studies identified CD36 and CD47 as dual biomarkers that can be used as patient stratifying tools and prognostic biomarkers for VT1021 treatment.

THBS1 belongs to a group of tumorigenic ECM proteins induced via TGFβ signaling in CRPC cells, and high expression of THBS1 in human prostate cancer tissues correlated with the degree of malignancy. TGFβ-induced production of THBS1 through TβRI facilitates the invasion and metastasis of CRPC cells as shown in vivo xenograft animal experiments.

THBS1 emerged as a novel biomarker for diagnosing NAFLD/MI in comparison to healthy controls. The results indicate that CD8+ T cells and neutrophils could serve as inflammatory immune features for differentiating patients with NAFLD/MI from healthy individuals.

Combination therapy of afatinib plus carboplatin (CBDCA) and pemetrexed (PEM) was effective in both parental and osimertinib-resistant cells. In PC-9-OR xenograft mouse models (five female Balb/c-Nude mice in each group), combination therapy strongly inhibited tumor growth compared with afatinib monotherapy (5 mg/kg, orally, five times per week) or CBDCA (75 mg/kg, intraperitoneally, one time per week) + PEM (100 mg/kg, intraperitoneally, one time per week) over a 28-day period. These results suggest that the combination of afatinib plus CBDCA and PEM, which effectively suppresses TSP-1 expression, may be a promising option in EGFR-mutated NSCLC patients after the acquisition of osimertinib resistance.

VT1021 is safe and well-tolerated in patients with solid tumors in a phase I expansion study. VT1021 has advanced to a phase II/III clinical study in glioblastoma (NCT03970447).

VT1021 is safe and well-tolerated across all doses tested. RP2D has been selected for future clinical studies. PR and SD with tumor shrinkage are observed in multiple patients underscoring the single-agent potential of VT1021. Expansion studies in GBM, pancreatic cancer and other solid tumors at the RP2D have been completed and results will be communicated in a separate report.

These results collectively suggest that THBS-1 represents an endogenous substrate of cereblon. This pairing is disrupted by IMiDs, and the aberrant accumulation of THBS-1 plays an important role in the pathogenesis of IMiDs-induced thromboembolism.

Blood samples were collected from 30 patients undergoing BeEAM/BEAM (bendamustine/carmustine, etoposide, cytarabine, melphalan) conditioning regimen at subsequent time points during AHSCT. Patients with a low concentration of THBS-1 had a higher risk of bacteremia and a shorter time to febrile neutropenia, indicating its potential value as a complications biomarker. Patients with lower serum THBS-1 concentrations, indicating an increased risk, may be more suitable for an inpatient AHSCT procedure, where close monitoring and immediate intervention are accessible.

We will discuss studies, mainly from preclinical research, which should lead to a deeper understanding of TSP1's role in GB development. We will also discuss some issues with regard to the use of this knowledge for the clinic.

GBM cells demonstrate augmented invasive capabilities following exposure to the current gold standard treatment of radiotherapy (RT) and concomitant and adjuvant temozolomide (TMZ), resulting in rapid disease recurrence...The preliminary data demonstrates that THBS1 is associated with invadopodia in GBM cells and is likely involved in the invadopodia-mediated invasive process in GBM cells exposed to RT/TMZ treatment. Therapeutic inhibition of THBS1-mediated invadopodia activity, which facilitates GBM cell invasion, should be further investigated as a treatment for GBM.

Low levels of ADAMTS-13 are associated with pathogenesis of PVT in liver cirrhosis. ADAMTS-13 concentration is potential biochemical marker in diagnostic strategy of PVT in patients with cirrhosis.

We will also review existing approaches to targeting CD36 in pre-clinical studies, as well as discuss the only CD36-targeting drug to advance to late-stage clinical trials, VT1021. Given the roles of CD36 in the etiology of metabolic disorders, such as atherosclerosis, diabetes, and non-alcoholic fatty liver disease, the clinical implications of CD36-targeted therapy are wide-reaching, even beyond cancer.

We further found that RNA-binding motif protein 5 (RBM5) suppressed IR induced by sulindac sulfide treatment...Furthermore, trans-chalcone demethylated TSP1V, thereby preventing methyl-CpG-binding protein 2 binding to TSP1V gene. In addition, TSP1V levels were significantly lower in patients with differentiated thyroid carcinoma than in those with benign thyroid nodule, indicating its potential application as a diagnostic biomarker in tumor progression.

At the molecular level, exosomal thrombospondin-1 was identified as a critical pro-TNT factor. These findings underline the influence of ECM stiffening on two diverse modes of cell communication and their interdependence, which may have significant implications in cancer biomedical research.

P1, N=116, Active, not recruiting, Vigeo Therapeutics, Inc. | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Dec 2022 --> Jan 2024

Our data suggest that OC patients with the highest CD47 expression profile at baseline have greatest lymphocyte influx post-NACT and may be most likely to benefit from post-operative immunotherapy. Whether blocking the immune-suppressive CD47:TSP1 interaction in this subset would provide an alternative strategy merits investigation. Clinical trial information: NCT01583322.

Mechanistically, LYN deletion reduces inflammatory signaling including reduction of c-JUN expression, which in turn augments the expression of Thrombospondin-1, which binds to CD47 thereby impairing CLL viability. Together, our findings suggest that LYN is essential for rewiring fibroblasts towards a leukemia-supportive phenotype.

As a result, the NRT-YHD_001 administration group showed significant therapeutic effect compared to sorafenib. These results showed that NRT-YHD_001 had a strong anticancer effect by converting the macrophage of don't eat me into eat me signal in the tumor microenvironment of liver cancer, thereby removing or inhibiting liver cancer cells.Keywords: let-7i-5p, macrophage, phagocytosis, liver cancer, NRT-YHD_001

Our preliminary study suggests that combining PHI and PCLX biomarkers may help to estimate, with higher accuracy, the presence of csPCa at initial diagnosis, allowing a personalized treatment approach. Further studies training the model on larger datasets are strongly encouraged to support the efficiency of this approach.

In this review, we summarize the current knowledge of mechanisms regulating PD-L1 expression, of the predictive value of TILs as well as of associated cellular and molecular components present in the TME in TNBC. Furthermore, TMB and emerging bio-markers with potential value in predicting efficacy of ICIs are discussed, and new therapeutic strategies will be outlined.

In vitro, PTE at concentrations without cytotoxicity also markedly suppressed NE-triggered B16 cell migration, prevented NE-induced TSP-1 proteolysis and reversed the expression of vimentin, N-cadherin and E-cadherin. PTE could block inflammation-enhanced tumor metastasis, and the underlying mechanism might be associated with the inhibition of NE-mediated TSP-1 degradation.

In summary, we found a key molecule-TSP1-that can predict and improve the sensitivity of ICC patients to gemcitabine chemotherapy, which is of great significance for the treatment of advanced cholangiocarcinoma.

When combined with mpMRI and prostate volume, Proclarix reliably predicted csPCa and ruled out men with no or indolent cancer. A large reduction of two thirds of unneeded biopsies was achieved. Proclarix can further be used with high confidence to reliably detect csPCa in men with an indeterminate PI-RADS 3 mpMRI. Despite these encouraging results, further validation is needed.

Thrombospondin-1 inhibited the induction of TIGIT, CD40LG, and MCL1 mRNAs following T cell activation in vitro. Increased mRNA expression of these T cell transcripts and MYCN in melanomas was associated with improved overall survival.

Further investigations are required to reveal the precise mechanisms of the antitumor effects of DUV irradiation and to facilitate its clinical application as a new therapy for pancreatic cancer. Overall, DUV irradiation can be potentially used as a therapeutic option of pancreatic malignancy.

MiR-3612 retarded NPC cell migration, adhesion, and proliferation by targeting THBS1 and inactivating the PI3K/AKT signaling pathway. This provides a novel therapeutic approach for NPC intervention.

Furthermore, xenograft tumor models showed that PKHB1 treatment could notably inhibit NSCLC tumor growth in vivo. In conclusion, these findings suggested that PKHB1 exerted antitumor efficacy in NSCLC via triggering ER stress-mediated but CD47-independent apoptosis, potentially functioned as a promising peptide-based therapeutic agent for NSCLC.

Moreover, high THBS1 expression was associated with poor survival in patients with CCA. Collectively, our study suggests that the increased expression of THBS1 by LLA promotes phenotypic alterations leading to CCA progression.

2010]CPO107 is a bispecific fusion protein based off the anti-CD20 ofatumumab antibody with one Fab fragment being replaced with a SIRPα domain, which natively binds CD47...The monoclonal antibody Magrolimab (Hu5F9-G4) in combination with rituximab induced a high rate of tolerable and durable complete responses in heavily pretreated patients (pts) with rituximab-refractory DLBCL and FL [Chao et al...Upon reaching the MTD or RP2D, Part B of the study will enroll approximately 15 pts with CD20+ NHL to explore preliminary efficacy. The study has been registered on ClinicalTrials.gov (NCT04853329).

CD47/TSP1 expression could serve as a marker to predict patient response to immune checkpoint blockade treatment, and targeting this pathway may preserve T cell activation, proliferation, effector function, and bioenergetics to reduce tumor burden as a monotherapy or in combination with anti-PD-1.

The absence of Thbs1 differentially regulated tryptophan and tricarboxylic acid cycle metabolites implicated in the progression of NAFLD. Overall, the lack of Thbs1 caused a significant shift in liver metabolism with potential implications for liver injury and the progression of NAFLD.

Based on the survival analysis, a TF-miRNA-mRNA sub-network, that is TFs (SPI1, HEY1, and CEBPB)-hsa-miR-338-3p-target genes (LAMC1 and THBS1) was established. In conclusion, the construction of a potential TF-related regulatory network will help elucidate the underlying pathological mechanisms of osteosarcoma, and may provide novel insights for the diagnosis and treatment of osteosarcoma.

At the molecular level, we provide evidence that the loss of miR-22 significantly affects the energetic metabolism and mitochondrial functions of hepatocytes, and the expression of tumor-promoting factors such as thrombospondin-1. Our study demonstrates that miR-22 acts as a hepatic tumor suppressor in vivo by restraining pro-carcinogenic metabolic deregulations through pleiotropic mechanisms and the overexpression of relevant oncogenes.

P=N/A, N=45, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P1, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2022 --> Dec 2022 | Trial primary completion date: Sep 2022 --> Dec 2022

TSP-1 derived from CAFs stimulates loss of Smad4 expression in cancer cells and accelerates malignant behavior by TGF-β signal activation in PDAC. TSP-1 could be a novel therapeutic target, not only for CAFs in stiff stroma, but also for cancer cells in the PDAC microenvironment.

However, the frequency and effector phenotypes of Cd47 CD8+ T cells were constrained in chronic LCMV-infected as well as in mice bearing B16 melanoma tumors. Therefore, CD47 regulates CD8+ T cell activation, proliferation, and fitness in a context-dependent manner.

Finally, TCGA-STAD data set was used to validate the expression levels of COL4A1, PDGFRB, and FN1. We found that 7 upregulated genes (i.e., PDGFRB, ANGPT2, VEGFC, COL4A2, COL4A1, THBS1, and FN1) were promising markers of prognosis in GC patients.

Irradiation can induce ESCC cells secreting DJ-1. Secreted DJ-1 enters bystander cells to initiate activation of the TGF-β1 pathway via the DJ-1/HSC70/Smad3 signaling axis. The TSP1/TGF-β1/Smad3 positive feedback pathway constitutes the core pathway that promotes ESCC metastasis. DJ-1 is a useful biomarker for predicting the efficacy of radiotherapy and a potential therapeutic target for reversing RIBE in ESCC. Schematic diagram showing the underlying mechanism that irradiation-induced secretion of DJ-1 accelerates the metastasis of bystander ESCC cells.