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Menin inhibitors are new and promising agents currently in clinical development that target the HOX/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A-rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemias. The mechanism of action of this new class of agents is based on the disruption of the menin–KMT2A complex (consisting of chromatin remodeling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or with mutated NPM1. To date, this new class of drugs has been tested in phase I and II clinical trials, both alone and in combination with synergistic drugs showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this brief review, we summarize the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data on the treatment of acute myeloid leukemia with this promising new class of agents, particularly revumenib and ziftomenib.

The identification of new effective therapeutic options for non-small-cell lung cancer (NSCLC) represents a crucial challenge in oncology. Recent studies indicate that cancer-associated fibroblasts (CAFs) participate in tumor progression by establishing a favorable microenvironment that promotes cancer progression. Therefore, the development of strategies inhibiting the interplay between CAFs and cancer cells is considered a winning approach for the development of effective anti-cancer drugs. Among other factors, the signal transducer and activator of transcription-3 (STAT3) has been reported as a key mediator of CAF oncogenic actions, representing a promising therapeutic target. Here, we applied an aptamer-based conjugate (named Gint4.T-STAT3), containing a STAT3 siRNA linked to an aptamer binding and inhibiting the platelet-derived growth factor receptor (PDGFR)β, to obtain STAT3-specific silencing and interfere with CAF pro-tumorigenic functions. We demonstrated that this molecule effectively delivers the STAT3 siRNA in NSCLC cells, and blocks CAF-induced cancer cell growth and migration and reduced spheroid dimension. In addition, we found that Gint4.T-STAT3 alters CAF phenotype, thus functioning as a double-acting molecule able to inhibit the entire tumor bulk. Our data provide a proof of principle for the targeting of CAF pro-tumor functions through an aptamer-based drug, and can open innovative horizons in NSCLC therapy.

Non-small-cell lung cancer (NSCLC) is the second most diagnosed type of malignancy and the first cause of cancer death worldwide. Despite recent advances, the treatment of choice for NSCLC patients remains to be chemotherapy, often showing very limited effectiveness with the frequent occurrence of drug-resistant phenotype and the lack of selectivity for tumor cells. Therefore, new effective and targeted therapeutics are needed. In this context, short RNA-based therapeutics, including Antisense Oligonucleotides (ASOs), microRNAs (miRNAs), short interfering (siRNA) and aptamers, represent a promising class of molecules. ASOs, miRNAs and siRNAs act by targeting and inhibiting specific mRNAs, thus showing an improved specificity compared to traditional anti-cancer drugs. Nucleic acid aptamers target and inhibit specific cancer-associated proteins, such as “nucleic acid antibodies”. Aptamers are also able of receptor-mediated cell internalization, and therefore, they can be used as carriers of secondary agents giving the possibility of producing very highly specific and effective therapeutics. This review provides an overview of the proposed applications of small RNAs for NSCLC treatment, highlighting their advantageous features and recent advancements in the field.

Incorrect pesticide use in plant protection often involve a risk to the health of operators and consumers and can have negative impacts on the environment and the crops. The application of artificial intelligence techniques can help the reduction of the volume sprayed, decreasing these impacts. In Italy, the production of ready-to-eat salad in greenhouses requires usually from 8 to 12 treatments per year. Moreover, inappropriate sprayers are frequently used, being originally designed for open-field operations. To solve this problem, a small vehicle suitable for moving over rough ground (named “rover”), was designed, able to carry out treatments based on a single row pass in the greenhouse, devoted to reduce significantly the sprayed product amount. To ascertain its potential, the prototype has been tested at two growth stages of some salad cultivars, adopting different nozzles and boom settings. Parameters such as boom height, nozzle spacing and inclination, pump pressure and rover traveling speed were studied. To assess the effectiveness of the spraying coverage, for each run several water-sensitive papers were placed throughout the vegetation. Compared to the commonly distributed mixture volume (1000 L/ha), the prototype is able to reduce up to 55% of product sprayed, but still assure an excellent crop coverage.