MYC positive

This study identifies MYC, FN1, BRCA1, and FGF2 as anoikis-related genes (ARGs) with significant regulatory roles in nasopharyngeal carcinoma (NPC). These ARGs are found to be involved in the development and progression of NPC, suggesting their potential as therapeutic targets for this cancer.

β(2)-MG (>2.3 μg/L) , Follicular lymphoma international prognostic index-1 (FLIPI-1) score (3-5 points) , negative CD37 expression, positive c-Myc expression, and TLG (>2 342.55 g) were all independent risk factors for PFS in the FL patients (HR=3.609, 2.509, 0.255, 3.506, 13.531, all P value<0.05) . (18)F-FDG PET-CT is a powerful complement to FL histopathological grading and the combination of the two may better predict the prognosis of FL patients.

Complete remission was maintained for over one year with lenalidomide maintenance therapy. A solitary IgH::MYC chromosomal translocation is extremely rare in multiple myeloma and may be associated with high tumor proliferative capacity, multiple extramedullary lesions, and poor prognosis. Combined therapeutic modalities with novel and conventional chemotherapy and radiation might be a promising treatment strategy for patients with this type of multiple myeloma.

Our results confirm that genomic alteration differs significantly between EBV-posDLBCL and EBV-negDLBCL, and reveal new genetic alterations in EBV-posDLBCL. The positive correlation of c-MET and PD-L1/c-Myc expression may be involved in the pathogenesis of EBV-posDLBCL, which is should be explored prospectively in trials involving MET-directed therapies.

Significantly, targeting CPT1A enhances immune checkpoint blockade-induced anti-tumor immunity and tumoral ferroptosis in tumor-bearing mice. The results illustrate the potential of a mechanism-guided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CSCs to improve the efficacy of lung cancer immunotherapy.

Our study provides insights into the clinical aspects of Myc family members in surgically resected SCLC tumors. Notably, besides showing that positivity of Myc family members varies across the patients, we also reveal that C-Myc protein expression independently correlates with worse survival outcomes. Further studies are warranted to investigate the role of Myc family members as potential prognostic and predictive markers in this hard-to-treat disease.

P1, N=54, Terminated, Pimera Australia Pty Ltd | Recruiting --> Terminated

These are 3 cases in a series of several other concordant results, nevertheless, elucidate limitations when interpreting FISH results in clinical applications, particularly when other genes are included in probe design. In addition, when the observed FISH signals are atypical, this study illustrates the necessity to perform complementary laboratory assays, such as NGS and/or RNASeq, to accurately identify fusion genes in tumorigenic translocations.

Further, correlations exist between MEF, c-Myc, and hnRNPK suggesting the MEF-c-Myc positive feedback loop is active in patients. Together these data demonstrate that MEF is a pivotal partner of the c-Myc network and propose MEF as a valuable therapeutic target for colorectal cancer.

We conclude that proportion of positive stains can be regressed using attention-based multiple instance learning, that these models generalize well to whole slide images, and that our models can provide non-inferior stratification of progression-free survival outcomes.

Additionally, upregulation of USP43 protein in BLCA increased the chance of interaction with c-Myc and interfered with FBXW7 access and degradation of c-Myc. These findings suggest that USP43 is a potential therapeutic target for indirectly targeting glycolytic metabolism and the c-Myc oncoprotein consequently enhancing the efficacy of bladder cancer treatment.

The incidence of MBCL with 11q abnormalities in children is low, clinical symptoms are mild, and progression is slow. The absence of MYC, BCL2, BCL6 rearrangements, C-MYC negative and 11q abnormalities on FISH is an important diagnostic indicator, and reducing the intensity of chemotherapy can improve prognosis.

Similar results were obtained by combining Talazoparib and different PARP inhibitors with the alkylating agent cisplatin, indicating a class effect. Importantly, PBMC-derived T cells from healthy donors did not show any sign of DNA damage accumulation upon exposure to Lonca, Talazoparib and the combination. These data provide the rationale for future therapeutic strategies based on selective induction of DNA damage in neoplastic B cells in combination with DDR inhibition in aggressive MYC-positive B cell lymphoma.

In conclusion, GZMB expression is highly heterogeneous in ENKTLs and is associated with the activation of the JAK-STAT3 pathway and higher MYC expression. GZMB-negative ENKTLs correlate with an advanced clinical stage, suggesting the potential utility of GZMB immunohistochemistry as a biomarker of ENKTL.

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy is the standard first-line treatment of DLBCL...Previous study has showed that ibrutinib combined with R-CHOP had improved event free survival (EFS) compared with placebo plus R-CHOP in non-GCB DLBCL patients with BCL2 and MYC co-expression (Johnson et al., Blood 2019)...Conclusions At the time of data cut-off 30 Jun 2023, 6 cycles of zanubrutinib combined with R-CHOP regimen was well tolerated and showed a promising response result in untreated non-GCB double-expression DLBCL patients. The study is ongoing and further results will be continuously released.

Ibrutinib demonstrated significant efficacy with manageable toxicities in previously untreated patients with high-risk smoldering MCL.

Our results support that the cooperation between MYC and XPO1 is associated with T-cell reductions characteristic of a Depleted or Cold TME, a key issue for CAR-T success. We applied the targeted therapies AZD4573 and Selinexor vs. cell line models to address this pathway, with both displaying anti-tumor effects as single agents.

P2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Feb 2026

Our results provide clinical insights into the diagnostic, prognostic and predictive significance of SCLC molecular subtype classifications.

The main objective of this study was to assess the application of the immunohistochemistry- and interphase fluorescence in situ hybridization (FISH)-based molecular markers in the diagnosis of DLBCL and its prognostic value in patients treated with rituximab-based immunochemotherapy...We did not find any difference in survival by GCB vs. non-GCB subtypes. These findings may improve prognostication in DLBCL and can contribute to designing further research in the area.

Based on our literature review, and is shown in this case, sporadic BL in adults shows some differences with the classic description of BL in children. We also discuss the differential diagnosis of BL.

In turn, MYC transactivated ESRRB and upregulated SMAD7, thus forming a positive feedback loop with ESRRB. Together, these findings identify the tumor promoting function of ESRRB in cervical cancer and reveal a mechanism by which ESRRB stimulates cell proliferation to promote cancer progression.

Cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab can be used in the chemotherapy regimen. This is a case of primary cardiac lymphoma (PCL) that encases the SVC and the aorta. PCL is a rare disease that can present with a variety of nonspecific cardiorespiratory symptoms. The case demonstrates that PCL can occur in immunocompetent individuals.

P2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Case Description/ A 63-year-old male with a history of coronary artery disease, on aspirin and clopidogrel, presented to the advanced endoscopy clinic for evaluation of GI bleeding with associated anemia...Numerous mitotic figures and apoptotic debris were also noted. (c) The large atypical lymphocytes express CD20 (10x objective) staining, consistent with B cell origin.

Decision was made to initiate EPOCH + Rituximab for treatment and to not pursue the full diagnostic workup of ScM. The patient would receive an alternative form of treatment for ScM of cyclophosphamide already in the EPOCH...This case helps support the theory of ScM being a paraneoplastic syndrome and a sign of underlying malignancies. Currently, there is no uniform recognized therapy, rather the whole clinical picture should be analyzed when determining the best treatment course of action for the patient.

Of these six genes, de novo CTP synthesis pathway enzyme CTPS1 whose inhibitor (STP938) is already in clinical trials for relapsed/refractory lymphomas (NCT05463263) has the highest regression coefficient. Additionally, MYC positively regulates CTPS1 expression, and TP53-aberrant and ibrutinib-resistant MCL cells also rely on cytidine metabolism. Furthermore, besides the obvious decreased CTP pool caused by CTPS1 deficiency, CTPS1 inhibition may also induce immune-related responses via activating dsDNA-cGAS-STING pathway, which plays a crucial role in impeding tumour growth in MCL patients.

Our study uncovers a precise mechanism that LINC00665 sustains BCa LN metastasis by inducing a RAB27B-HGF-c-Myc positive feedback loop between BCa cells and fibroblasts, suggesting that LINC00665 could be a promising therapeutic target for patients with LN metastatic BCa.

In patients with colorectal adenocarcinoma, increased MYC expression by neoplastic cells is associated with increased densities of adaptive immune cells in the tumor microenvironment. In addition, it is associated with a favorable prognosis, possibly through a more effective antitumor immune response. Consequently, the expression of MYC might be a useful predicting indicator of anti-tumor immunity status and patient's prognosis.

Our work revealed for the first time that NR_109 exerted a crucial role in regulating the phenotype-remodeling and function of M2-like macrophages via a NR_109/FUBP1/c-Myc positive feedback loop. Thus, NR_109 has great translational potentials in the diagnosis, prognosis and immunotherapy of cancer.

However, with larger numbers of DEL cases available in mRNA-based measurement cohorts, there was a statistically significant stratification for PFS (GSE117556: OS, p = 0.084, PFS, p = 0.031; GOYA: OS, p = 0.065, PFS, p = 0.047), suggesting that the following formula refines the current DEL definition and improves its prognostic value: Using a pan-immune protein-marker DSP panel, we identified that the T-cell immune regulators ICOS and 4-1BB were negatively correlated with M+2+6- percentage extent (r = −0.27, p = 0.0046; r = −0.22, p = 0.019, respectively), suggesting a potential role for ICOS or 4-1BB stimulatory therapeutics (e.g. feladilimab, utomilumab) in combination with chemotherapy for high M+2+6- cases. A simple mathematical formula for estimation of MYC+BCL2+BCL6- cells in DLBCL refines the DEL diagnosis, and could be of value in selecting high risk DLBCL for trials of novel agents. High M+2+6- DLBCL display unique T-cell infiltrates, and immunomodulation by ICOS and 4-1BB agonists could represent a therapeutic vulnerability for this high-risk subgroup.

Pharmacological inhibition of EZH2 using EPZ005687 attenuated MB cell viability and reduced the expression of B7‑H3...Further, EZH2 silencing induced apoptosis and reduced colony‑forming ability in MB cells, whereas EZH2 inhibition in MYC‑amplified C17.2 neural stem cells induced G2/M phase arrest while downregulating B7‑H3 expression. Collectively, the current study positions EZH2 as a viable target for the future development of MB treatments and that targeting EZH2 in combination with B7‑H3 immunotherapy may be an effective treatment for halting MB progression.

In turn, MYC increases expression of POLD1, forming a POLD1-MYC positive feedback loop to enhance the pro-carcinogenic effect of POLD1-MYC on BLCA. Overall, our study identifies POLD1 as a promotor of BCLA via a MYC driven mechanism and suggest its potential as biomarker for BLCA.

This held true even within the first 120 days after the start of therapy: an increase in the ADC value corresponds to a probable response to therapy, while a decrease predicts progression. Minimal or no changes were seen in cases of stable disease.

P2, N=22, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2023 --> Feb 2024

The prognosis of PCL is poor and the only significant predictor for improved mortality is chemotherapy(3). Treatment is often delayed by confirmation of the diagnosis, but we present a unique case of cardiac lymphoma diagnosed by EBUS with biopsy of the metastatic disease and spared the patient from an invasive cardiac biopsy.

Comprehensive genomic profiling helps identify multiple molecular prognostic and/or predictive biomarkers that could predict patients’ clinical outcomes to nCRT and TME and direct nCRT treatment regimen, thus facilitating more accurate prognostic estimation, a better balance between treatment efficacy and quality of life, and timely adjusted treatment decisions.

Our work suggests that targeting G9a could prove to be a potential therapeutic avenue for Myc-driven liver cancer. This will increase our understanding of the underlying epigenetic mechanisms of aggressive tumor initiation and lead to improved therapeutic and diagnostic options for Myc-driven hepatic tumors.

A tendency of poor OS was seen in p53 patients in the non-GCB, GCB, and double expressors subgroups and poor PFS in p53 patients regardless of the subgrouping. In conclusion, our results suggest that p63 and p53 may represent potential additional prognostic biomarkers in DLBCL and may be included in the initial diagnostic work up of patients with DLBCL.

A total of 110 patients diagnosed with DLBCL-NOS from 2012 to 2020 at Tottori University Hospital and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy were included. The 2-year survival rates were 100%, 83.0%, and 47.1% for the groups 1, 2, and 3, respectively (P < 0.0001). We suggest that a prognostic scoring system using MYC expression and soluble interleukin receptor -2 level is useful for the prediction of prognosis, contributing to further stratification in DLBCL-NOS.