Volume 2 Issue 11, November 2021

The mechanisms regulating the progression of benign tumors to malignant carcinomas remain incompletely understood. A new study identifies the transcription factor NR2F2 as a specific regulator of this transition that plays critical roles in the maintenance of the malignant tumor state.

Glioblastoma multiforme (GBM) is a lethal form of primary brain cancer. A new study now implicates beta-secretase 1 (BACE1) as a crucial regulator of pro-tumoral IL-6–STAT3 signaling in GBM-associated macrophages. An effective BACE1 inhibitor, clinically developed for Alzheimer’s disease, may offer new hope for GBM treatment.

Acute myeloid leukemia (AML) is a heterogeneous disease with limited therapeutic options. A new study identifies leukocyte immunoglobulin-like receptor 3 (LILRB3) as a marker of monocytic AML, with the ability to modulate NF-κB signaling and to promote survival and immune evasion. Blockade of LILRB3 signaling could provide a novel therapeutic strategy in monocytic AML.

Ting and colleagues report the safety and efficacy of combined radiation and immunotherapy in a phase II trial on patients with MSS colorectal or pancreatic cancer and observe that disease control correlates with higher repetitive RNA transcription.

Zhai et al. identify clinical brain-penetrant BACE1 inhibitors as regulators of macrophage-dependent phagocytosis in glioblastoma through IL-6–STAT3 signaling and demonstrate preclinical therapeutic efficacy in orthotopic mouse models and PDXs.

Blanpain and colleagues identify NR2F2 as a regulator of stemness and invasiveness that promotes tumor renewal and restricts differentiation to sustain squamous cell carcinomas.

Wu et al. show that LILRB3 modulates AML cell survival and antileukemic T-cell responses through regulation of TRAF2–cFLIP–NF-κB signaling and demonstrate the therapeutic efficacy of LILRB3-blocking antibodies in humanized PDX models in vivo.

Singh and colleagues show that PDAC phenotypic plasticity is regulated via AP1 enhancer remodeling and modulated by TNF-α⁺ macrophages and pharmacological inhibition of the BRD4–cJUN–CCL2–TNF-α axis restores favorable PDAC subtypes and prognosis.

Sarry and colleagues demonstrate that adaptive resistance to venetoclax + cytarabine therapy in acute myeloid leukemia relies on mitochondrial respiration and show that combination with electron transport chain complex inhibitors delays relapse in patient-derived xenograft models in vivo.

Lehtiö and colleagues perform proteogenomic analysis of non-small cell lung cancer and identify molecular subtypes with distinct immune-evasion mechanisms and therapeutic targets and validate their classification method in separate clinical cohorts.