Heather J. DiBenedetto

Data from MTA-Cooperative PRMT5 Inhibitors Are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models

Xiaochun Zhang, Dana C. Borcherding, Minjie Zhang, Yang Lyu et autres

AbstractPurpose: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive sarcomas with poor prognosis. The enzyme methylthioadenosine phosphorylase (MTAP) is lost in ∼25% to 50% of MPNSTs, which is associated with loss of the tumor suppressor gene CDKN2A. Inhibition of PRMT5 was …

Supplemental Figure 4 from MTA-Cooperative PRMT5 Inhibitors Are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models

Xiaochun Zhang, Dana C. Borcherding, Minjie Zhang, Yang Lyu et autres

Supplemental Figure 4. Additive effect of combination of chemotherapeutic drug and MTA-cooperative PRMT5 inhibitor on cell viability in MPNST cell lines.

Supplemental Figure 3 from MTA-Cooperative PRMT5 Inhibitors Are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models

Xiaochun Zhang, Dana C. Borcherding, Minjie Zhang, Yang Lyu et autres

Supplemental Figure 3. Common chemotherapeutic drugs are effective in MPNST cell lines but are not selective for cancer cells.

Supplemental Figure 6 from MTA-Cooperative PRMT5 Inhibitors Are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models

Xiaochun Zhang, Dana C. Borcherding, Minjie Zhang, Yang Lyu et autres

Supplemental Figure 6. TNG908 and TNG462 are well-tolerated in mice.

Supplemental Figure 2 from MTA-Cooperative PRMT5 Inhibitors Are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models

Xiaochun Zhang, Dana C. Borcherding, Minjie Zhang, Yang Lyu et autres

Supplemental Figure 2. The SAM-cooperative PRMT5 inhibitor GSK3326595 is not selective for MTAP status in MPNST cell lines.

Supplemental Figure 1 from MTA-Cooperative PRMT5 Inhibitors Are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models

Xiaochun Zhang, Dana C. Borcherding, Minjie Zhang, Yang Lyu et autres

Supplemental Figure 1. MTA-cooperative PRMT5 inhibitors target cells with MTAP deletion.

Supplemental Figure 5 from MTA-Cooperative PRMT5 Inhibitors Are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models

Xiaochun Zhang, Dana C. Borcherding, Minjie Zhang, Yang Lyu et autres

Supplemental Figure 5. TNG462 treatment is necessary for durable tumor regressions in WU-356 model.

DDDR-64. MTA-Cooperative PRMT5 Inhibitors Demonstrate Efficacy in MTAP-Deleted MPNST Models and Enhance Chemotherapy Response

Xinyang Zhang, Dana C. Borcherding, Minjie Zhang, Yang Lyn et autres

Abstract Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive soft tissue sarcomas with limited treatment options and poor prognosis, underscoring the urgent need for novel targeted therapies. Approximately 25-50% of MPNSTs harbor homozygous deletion of methylthioadenosine phosphorylase (MTAP) due to co-deletion …

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Supplemental Table 6 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes STK11-Mutant Tumors to Anti–PD-1 Immunotherapy

Leanne G. Ahronian, Soumyadip Sahu, Minjie Zhang, Ayushi S. Patel et autres

10 patients with STK11-deficient solid tumors enrolled in NCT05887492 provided paired biopsies during Phase 1

Data from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes STK11-Mutant Tumors to Anti–PD-1 Immunotherapy

Leanne G. Ahronian, Soumyadip Sahu, Minjie Zhang, Ayushi S. Patel et autres

Abstract Patients with non–small cell lung cancer (NSCLC) with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti–PD-1. In this study, we conducted an in vivo CRISPR screen that identified histone deacetylase 1 as a target …

Supplemental Figure 3 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes STK11-Mutant Tumors to Anti–PD-1 Immunotherapy

Leanne G. Ahronian, Soumyadip Sahu, Minjie Zhang, Ayushi S. Patel et autres

TNG260 is selective against HDAC3-9, 11

Supplemental Figure 2 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes STK11-Mutant Tumors to Anti–PD-1 Immunotherapy

Leanne G. Ahronian, Soumyadip Sahu, Minjie Zhang, Ayushi S. Patel et autres

In-vivo immune sensitizer screen in STK11-isogenic MC38 tumors