Palmitoyltransferase ZDHHC3 is essential for the oncogenic activity of PML/RARα in acute promyelocytic leukemia.

The oncogenic fusion protein promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα) is critical for acute promyelocytic leukemia (APL). PML/RARα initiates APL by blocking the differentiation and increasing the self-renewal of leukemic cells. The standard clinical therapies all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which induce PML/RARα proteolysis, have dramatically improved the prognosis of APL patients.

The palmitoyltransferase ZDHHC21 regulates oxidative phosphorylation to induce differentiation block and stemness in AML.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of patients who receive the most intensive treatment inevitably experience disease relapse, likely resulting from the persistence of drug-resistant leukemia stem cells (LSCs). AML cells, especially LSCs, are highly dependent on mitochondrial oxidative phosphorylation (OXPHOS) for survival, but the mechanism involved in OXPHOS hyperactivity is unclear, and a noncytotoxic strategy to inhibit OXPHOS is lacking.

AKT inhibitor Hu7691 induces differentiation of neuroblastoma cells.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options.

Deneddylation of PML/RARα reconstructs functional PML nuclear bodies via orchestrating phase separation to eradicate APL.

Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML/RARα, which destroys the architecture of PML nuclear bodies (NBs). PML NBs are critical to tumor suppression, and their disruption mediated by PML/RARα accelerates APL pathogenesis. However, the mechanisms of PML NB disruption remain elusive.

Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy.

The discovery of effective therapeutic treatments for cancer via cell differentiation instead of antiproliferation remains a great challenge. Cyclin-dependent kinase 2 (CDK2) inactivation, which overcomes the differentiation arrest of acute myeloid leukemia (AML) cells, may be a promising method for AML treatment. However, there is no available selective CDK2 inhibitor.

The role of autophagy in targeted therapy for acute myeloid leukemia.

Although molecular targeted therapies have recently displayed therapeutic effects in acute myeloid leukemia (AML), limited response and acquired resistance remain common problems. Numerous studies have associated autophagy, an essential degradation process involved in the cellular response to stress, with the development and therapeutic response of cancers including AML. Thus, we review studies on the role of autophagy in AML development and summarize the linkage between autophagy and several recurrent genetic abnormalities in AML, highlighting the potential of capitalizing on autophagy modulation in targeted therapy for AML.

Protein phase separation: A novel therapy for cancer?

In recent years, phase separation has been increasingly reported to play a pivotal role in a wide range of biological processes. Due to the close relationships between cancer and disorders in intracellular physiological function, the identification of new mechanisms involved in intracellular regulation has been regarded as a new direction for cancer therapy. Introducing the concept of phase separation into complex descriptions of disease mechanisms may provide many different insights.

CDK2 suppression synergizes with all-trans-retinoic acid to overcome the myeloid differentiation blockade of AML cells.

A characteristic feature of leukemia cells is a blockade of differentiation in cellular maturation. All-trans-retinoic acid (ATRA) has been successfully applied for the treatment of M3-type AML (APL, 10 %), but it fails to demonstrate a significant efficacy on the remaining patients with non-APL AML (90 %). Therefore, the research for strategies to extend the efficacy of ATRA-based therapy to non-APL AML is a key avenue of investigation.

Post-translational modification of retinoic acid receptor alpha and its roles in tumor cell differentiation.

Retinoic acid (RA) is a well-known differentiation inducer that exerts its effects by binding to nuclear RA receptors. Retinoic acid receptor α (RARα), as an important nuclear RA receptor, is activated upon RA binding and facilitates the transcription of target genes related to differentiation, which ultimately initiates cell differentiation. Previous studies have found that the transcriptional activity of RARα is regulated by various post-translational modifications, which influence its DNA binding efficiency, transactivation ability and even lead to degradation.

Carrier-Free, Pure Nanodrug Formed by the Self-Assembly of an Anticancer Drug for Cancer Immune Therapy.

Ursolic acid (UA) is a food-plant-derived natural product which has good anticancer activities and low toxicity. However, the poor water solubility of UA limits its application in clinic. To address this issue, we developed a carrier-free nanodrug by self-assembly of UA.

Synergistic Chemopreventive and Therapeutic Effects of Co-drug UA-Met: Implication in Tumor Metastasis.

The anticancer properties of ursolic acid (UA) and metformin (Met) have been well demonstrated. However, whether these compounds can act synergistically to prevent and treat cancer is not known. We present in this study, the synergism between UA and Met, and that of a new codrug made of UA and Met (UA-Met) against several cancer cell lines.

Metapristone (RU486 metabolite) suppresses NSCLC by targeting EGFR-mediated PI3K/AKT pathway.

Therapies targeting epidermal growth factor receptor (EGFR) can effectively treat with non-small cell lung cancer (NSCLC), but NSCLC's drug resistance makes it intractable. Herein, we showed that RU486 metabolite metapristone inhibited the proliferation of various NSCLC cell lines with either wild (A549, H1299, H520) or mutated EGFR (H1975, HCC827). The suppression was resulted from inhibition by metapristone of EGFR signaling pathways through down-regulating the EGFR, PTEN, as well as AKT and ERK proteins.

Co-delivery of sorafenib and siVEGF based on mesoporous silica nanoparticles for ASGPR mediated targeted HCC therapy.

Combination with chemotherapeutic drug and gene therapy has been proven highly effective in suppressing tumor progression. Hence, an asialoglycoprotein receptor (ASGPR)-targeting nanodrug delivery system based on mesoporous silica (MSN) nanocarrier for co-delivery of sorafenib (SO) and vascular endothelial growth factor (VEGF) targeted siRNA (siVEGF) to hepatocellular carcinoma (HCC) was successfully designed and synthesized. The structure of nanoparticles was characterized by IR, particle size, zeta potential and N2 adsorption-desorption.

Dual-Targeting Multifuntional Mesoporous Silica Nanocarrier for Codelivery of siRNA and Ursolic Acid to Folate Receptor Overexpressing Cancer Cells.

A targeting drug delivery system (TDDS) can selectively deliver antitumor drugs to cancerous parts to improve its anticancer efficacy. Hence, a targeted drug delivery system (UA/siVEGF@MSN-FA) coloading ursolic acid (UA) and vascular endothelial growth factor (VEGF) targeted siRNA (siVEGF) based on mesoporous silica (MSN) nanocarrier modified by a folic acid (FA) molecule was designed and synthesized. The MSN-FA nanoparticles were investigated for shape, diameter, and zeta potential and and by infrared (IR) spectroscopy.