From the identification of actionable molecular targets to the generation of faithful neuroblastoma patient-derived preclinical models.

Background: Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Although the overall survival of patients with NB has improved in the last years, more than 50% of high-risk patients still undergo a relapse. Thus, in the era of precision/personalized medicine, the need for high-risk NB patient-specific therapies is urgent.

Neuroblastoma is associated with alterations in gut microbiome composition subsequent to maternal microbial seeding.

Background: Neuroblastoma is the most frequent extracranial solid tumour in children, accounting for ∼15% of deaths due to cancer in childhood. The most common clinical presentation are abdominal tumours. An altered gut microbiome composition has been linked to multiple cancer types, and reported in murine models of neuroblastoma.

Antitumor activity of the investigational B7-H3 antibody-drug conjugate, vobramitamab duocarmazine, in preclinical models of neuroblastoma.

Introduction: B7-H3 is a potential target for pediatric cancers, including neuroblastoma (NB). Vobramitamab duocarmazine (also referred to as MGC018 and herein referred to as vobra duo) is an investigational duocarmycin-based antibody-drug conjugate (ADC) directed against the B7-H3 antigen. It is composed of an anti-B7-H3 humanized IgG1/kappa monoclonal antibody chemically conjugated through a cleavable valine-citrulline linker to a ocarmycin-hydroxyenzamide zaindole (vc-seco-DUBA).

Therapeutic Targeting of ALK in Neuroblastoma: Experience of Italian Precision Medicine in Pediatric Oncology.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Patients with relapsed/refractory disease have a poor prognosis, and additional therapeutic options are needed. Mutations and amplifications in the (Anaplastic Lymphoma Kinase) gene constitute a key target for treatment.

The person-to-person transmission landscape of the gut and oral microbiomes.

The human microbiome is an integral component of the human body and a co-determinant of several health conditions. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns.

Augmented efficacy of nano-formulated docetaxel plus curcumin in orthotopic models of neuroblastoma.

Neuroblastoma is a biologically heterogeneous extracranial tumor, derived from the sympathetic nervous system, that affects most often the pediatric population. Therapeutic strategies relying on aggressive chemotherapy, surgery, radiotherapy, and immunotherapy have a negative outcome in advanced or recurrent disease. Here, spherical polymeric nanomedicines (SPN) are engineered to co-deliver a potent combination therapy, including the cytotoxic docetaxel (DTXL) and the natural wide-spectrum anti-inflammatory curcumin (CURC).

Combined mitoxantrone and anti-TGFβ treatment with PD-1 blockade enhances antitumor immunity by remodelling the tumor immune landscape in neuroblastoma.

Background: Poor infiltration of functioning T cells renders tumors unresponsive to checkpoint-blocking immunotherapies. Here, we identified a combinatorial in situ immunomodulation strategy based on the administration of selected immunogenic drugs and immunotherapy to sensitize poorly T-cell-infiltrated neuroblastoma (NB) to the host antitumor immune response.

Methods: 975A2 and 9464D NB cell lines derived from spontaneous tumors of TH-MYCN transgenic mice were employed to study drug combinations able of enhancing the antitumor immune response using in vivo and ex vivo approaches.

Italian Precision Medicine in Pediatric Oncology: Moving beyond Actionable Alterations.

Neuroblastoma (NB) is the most common extracranial solid tumor encountered in childhood. Although there has been significant improvement in the outcomes of patients with high-risk disease, the prognosis for patients with metastatic relapse or refractory disease is poor. Hence, the clinical integration of genome sequencing into standard clinical practice is necessary in order to develop personalized therapy for children with relapsed or refractory disease.

Nucleolin expression has prognostic value in neuroblastoma patients.

Background: Neuroblastoma (NB) represents the most frequent form of extra-cranial solid tumour of infants, responsible for 15% of childhood cancer deaths. Nucleolin (NCL) prognostic value in NB was investigated.

Methods: NCL protein expression was retrospectively evaluated in tumour samples of NB patients at diagnosis and after chemotherapy.

The Pyrazolo[3,4-]Pyrimidine Derivative Si306 Encapsulated into Anti-GD2-Immunoliposomes as Therapeutic Treatment of Neuroblastoma.

Si306, a pyrazolo[3,4-]pyrimidine derivative recently identified as promising anticancer agent, has shown favorable in vitro and in vivo activity profile against neuroblastoma (NB) models by acting as a competitive inhibitor of c-Src tyrosine kinase. Nevertheless, Si306 antitumor activity is associated with sub-optimal aqueous solubility, which might hinder its further development. Drug delivery systems were here developed with the aim to overcome this limitation, obtaining suitable formulations for more efficacious in vivo use.

Recent advances in the developmental origin of neuroblastoma: an overview.

Neuroblastoma (NB) is a pediatric tumor that originates from neural crest-derived cells undergoing a defective differentiation due to genomic and epigenetic impairments. Therefore, NB may arise at any final site reached by migrating neural crest cells (NCCs) and their progeny, preferentially in the adrenal medulla or in the para-spinal ganglia.NB shows a remarkable genetic heterogeneity including several chromosome/gene alterations and deregulated expression of key oncogenes that drive tumor initiation and promote disease progression.

Retinoids Delivery Systems in Cancer: Liposomal Fenretinide for Neuroectodermal-Derived Tumors.

Retinoids are a class of natural and synthetic compounds derived from vitamin A. They are involved in several biological processes like embryogenesis, reproduction, vision, growth, inflammation, differentiation, proliferation, and apoptosis. In light of their important functions, retinoids have been widely investigated for their therapeutic applications.

A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors.

MYCN drives aggressive behavior and refractoriness to chemotherapy, in several tumors. Since MYCN inactivation in clinical settings is not achievable, alternative vulnerabilities of MYCN-driven tumors need to be explored to identify more effective and less toxic therapies. We previously demonstrated that PARP inhibitors enhance MYCN-induced replication stress and promote mitotic catastrophe, counteracted by CHK1.

The Olive Leaves Extract Has Anti-Tumor Effects against Neuroblastoma through Inhibition of Cell Proliferation and Induction of Apoptosis.

Neuroblastoma (NB) is the most common extra-cranial solid tumor of pediatric age. The prognosis for high-risk NB patients remains poor, and new treatment strategies are desirable. The olive leaf extract (OLE) is constituted by phenolic compounds, whose health beneficial effects were reported.

Cotargeting of miR-126-3p and miR-221-3p inhibits PIK3R2 and PTEN, reducing lung cancer growth and metastasis by blocking AKT and CXCR4 signalling.

Lung cancer is the leading cause of cancer-related death worldwide. Late diagnosis and metastatic dissemination contribute to its low survival rate. Since microRNA (miRNA) deregulation triggers lung carcinogenesis, miRNAs might represent an interesting therapeutic tool for lung cancer management.

Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy.

Background: Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Nucleolin (NCL) is a protein overexpressed and partially localized on the cell surface of tumor cells of adult cancers. Little is known about NCL and pediatric tumors and nothing is reported about cell surface NCL and NB.

Bone Marrow Environment in Metastatic Neuroblastoma.

The study of the interactions occurring in the BM environment has been facilitated by the peculiar nature of metastatic NB. In fact: (i) metastases are present at diagnosis; (ii) metastases are confined in a very specific tissue, the BM, suggestive of a strong attraction and possibility of survival; (iii) differently from adult cancers, NB metastases are available because the diagnostic procedures require morphological examination of BM; (iv) NB metastatic cells express surface antigens that allow enrichment of NB metastatic cells by immune-magnetic separation; and (v) patients with localized disease represent an internal control to discriminate specific alterations occurring in the metastatic niche from generic alterations determined by the neoplastic growth at the primary site. Here, we first review the information regarding the features of BM-infiltrating NB cells.

Enhanced therapeutic index of liposomal doxorubicin Myocet locally delivered by fibrin gels in immunodeficient mice bearing human neuroblastoma.

Caelyx and Myocet are clinically used liposomal forms of doxorubicin (Dox). To explore ways to improve their therapeutic index, we have studied their activity in vitro and in vivo when locally delivered by fibrin gels (FBGs). In vivo local toxic and anti-tumour activities of loaded FBGs were assessed in two immunodeficient mouse orthotopic human neuroblastoma (NB) models after application in the visceral space above the adrenal gland, either still tumour-bearing or after tumour removal.

Targeting Vesicular LGALS3BP by an Antibody-Drug Conjugate as Novel Therapeutic Strategy for Neuroblastoma.

Neuroblastoma is the most common extra-cranial solid tumor in infants and children, which accounts for approximately 15% of all cancer-related deaths in the pediatric population. New therapeutic modalities are urgently needed. Antibody-Drug Conjugates (ADC)s-based therapy has been proposed as potential strategy to treat this pediatric malignancy.

Gut Bacteria and their Metabolites: Which One Is the Defendant for Colorectal Cancer?

Colorectal cancer (CRC) is a worldwide health concern which requires efficient therapeutic strategies. The mechanisms underlying CRC remain an essential subject of investigations in the cancer biology field. The evaluation of human microbiota can be critical in this regard, since the disruption of the normal community of gut bacteria is an important issue in the development of CRC.