Macrophages are critical mediators of tissue homeostasis, with the function of tissue development and repair, but also in defense against pathogens. Tumor-associated macrophages (TAMs) are considered as the main component in the tumor microenvironment and play an important role in tumor initiation, growth, invasion, and metastasis. Recently, metabolic studies have revealeded specific metabolic pathways in macrophages are tightly associated with their phenotype and function. Generally, pro-inflammatory macrophages (M1) rely mainly on glycolysis and exhibit impairment of the tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation (OXPHOS), whereas anti-inflammatory macrophages (M2) are more dependent on mitochondrial OXPHOS. However, accumulating evidence suggests that macrophage metabolism is not as simple as previously thought. This review discusses recent advances in immunometabolism and describes how metabolism determines macrophage phenotype and function. In addition, we describe the metabolic characteristics of TAMs as well as their therapeutic implications. Finally, we discuss recent obstacles facing this area as well as promising directions for future study.

RNA demethylase ALKBH5 takes part in the modulation of N⁶-methyladenosine (m⁶A) modification and controls various cell processes. ALKBH5-mediated m⁶A demethylation regulates gene expression by affecting multiple events in RNA metabolism, e.g., pre-mRNA processing, mRNA decay and translation. Mounting evidence shows that ALKBH5 plays critical roles in a variety of human malignancies, mostly via post-transcriptional regulation of oncogenes or tumor suppressors in an m⁶A-dependent manner. Meanwhile, increasing non-coding RNAs are recognized as functional targets of ALKBH5 in cancers. Here we reviewed up-to-date findings about the pathological roles of ALKBH5 in cancer, the molecular mechanisms by which it exerts its functions, as well as the underlying mechanism of its dysregulation. We also discussed the therapeutic implications of targeting ALKBH5 in cancer and potential ALKBH5-targeting strategies.

Metformin is a standard clinical drug used to treat type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome. Recently, epidemiological studies and meta‑analyses have revealed that patients with T2DM have a lower incidence of tumor development than healthy controls and that patients diagnosed with cancer have a lower risk of mortality when treated with metformin, demonstrating an association between metformin and tumorigenesis. In vivo and in vitro studies have revealed that metformin has a direct antitumor effect, which may depress tumor proliferation and induce the apoptosis, autophagy and cell cycle arrest of tumor cells. The mechanism underpinning the antitumor effect of metformin has not been well established. Studies have demonstrated that reducing insulin and insulin‑like growth factor levels in the peripheral blood circulation may lead to the inhibition of phosphoinositide 3‑kinase/Akt/mechanistic target of rapamycin (mTOR) signaling or activation of AMP‑activated protein kinase, which inhibits mTOR signaling, a process that may be associated with the antitumor effect of metformin. The present review primarily focuses on the recent progress in understanding the function of metformin in tumor development.

Chemotherapy-induced peripheral neuropathy (CIPN) seriously affects the quality of life of patients with multiple myeloma (MM) as well as the response rate to chemotherapy. Acupuncture has a potential role in the treatment of CIPN, but at present there have been no randomized clinical research studies to analyze the effectiveness of acupuncture for the treatment of CIPN, particularly in MM patients. The MM patients (104 individuals) who met the inclusion criteria were randomly assigned into a solely methylcobalamin therapy group (500 μg intramuscular methylcobalamin injections every other day for 20 days; ten injections) followed by 2 months of 500 μg oral methylcobalamin administration, three times per day) and an acupuncture combined with methylcobalamin (Met + Acu) group (methylcobalamin used the same way as above accompanied by three cycles of acupuncture). Of the patients, 98 out of 104 completed the treatment and follow-ups. There were 49 patients in each group. The evaluating parameters included the visual analogue scale (VAS) pain score, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire scores, and electromyographic (EMG) nerve conduction velocity (NCV) determinations. We evaluated the changes of the parameters in each group before and after the therapies and made a comparison between the two groups. After 84 days (three cycles) of therapy, the pain was significantly alleviated in both groups, with a significantly higher decrease in the acupuncture treated group (P < 0.01). The patients’ daily activity evaluated by Fact/GOG-Ntx questionnaires significantly improved in the Met + Acu group (P < 0.001). The NCV in the Met + Acu group improved significantly while amelioration in the control group was not observed. The present study suggests that acupuncture combined with methylcobalamin in the treatment of CIPN showed a better outcome than methylcobalamin administration alone. China Clinical Trials Register (registration no. ChiCTR-INR-16009079 , registration date August 24, 2016).

Tumorigenesis, tumor growth, and prognosis are highly related to gene alterations and post-translational modifications (PTMs). Ubiquitination is a critical PTM that governs practically all aspects of cellular function. An increasing number of studies show that E3 ubiquitin ligases (E3s) are important enzymes in the process of ubiquitination that primarily determine substrate specificity and thus need to be tightly controlled. Among E3s, neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) has been shown to play a critical role in modulating the proliferation, migration, and invasion of cancer cells and the sensitivity of cancer cells to anticancer therapies via regulating multiple substrates. This review discusses some significant discoveries on NEDD4-1 substrates and the signaling pathways in which NEDD4-1 participates. In addition, we introduce the latest potential therapeutic strategies that inhibit or activate NEDD4-1 activity using small molecules. NEDD4-1 likely acts as a novel drug target or diagnostic marker in the battle against cancer.