Stage 4S specifies a metastatic disease in children under the age of one year, which may undergo spontaneous regression, usually associated with 90% survival rate at 5 years. Stage 3 and stage 4 comprehends patients with metastatic disease. Accordingly, stages 1, 2A and 2B include patients with localized tumor, without propagation to lymph nodes. Namely, the degree of surgical excision of primary tumor, lymph node involvement, dissemination to distant organs, degree of bone marrow involvement and the age of infant. Given the high heterogeneous features of NB, the International Neuroblastoma Staging System (INSS), considers a plethora of criteria to rank patients. NB is a complex disease with different outcomes, going from metastasis to one or more distant sites to spontaneous regression or differentiation, even in the absence of any specific treatment. Tumors arising along the spinal column can expand through the intraforaminal spaces and cause cord compression, with resulting paralysis. Primary tumors in the neck or upper chest can cause Horner’s syndrome (ptosis, miosis, and anhidrosis). The majority of these tumors develop in the adrenal medulla however, NB can arise anywhere along the sympathetic nervous system (neck, chest, abdomen or pelvis).

It originates from primitive sympathetic neural precursor cells of the peripheral nervous system. Neuroblastoma (NB) is the most frequent embryonic malignancy among children particularly before 5 years of age. We highlight the potential clinical impact of SRCIN1/p140Cap expression in neuroblastoma tumors, in terms of reducing cytotoxic effects of chemotherapy, one of the main issues for pediatric tumor treatment. Overall, we provide the first evidence that SRCIN1/p140Cap is a new independent prognostic marker for patient outcome and treatment, with a causal role in curbing the aggressiveness of neuroblastoma. p140Cap also contributes to an increased sensitivity of neuroblastoma cells to chemotherapy drugs and to the combined usage of doxorubicin and etoposide with Src inhibitors. Moreover, p140Cap expression decreases in vitro migration and anchorage-independent cell growth, and impairs in vivo tumor progression, in terms of tumor volume and number of spontaneous lung metastasis. Functional assays demonstrated that p140Cap is causal in dampening both Src and Jak2 kinase activation and STAT3 phosphorylation. In high-risk patients, SRCIN1 was frequently altered by hemizygous deletion, copy-neutral loss of heterozygosity, or disruption. RNA-Seq profiles of a large cohort of neuroblastoma patients show that SRCIN1 mRNA levels are an independent risk factor inversely correlated to disease aggressiveness. Here we analyze the role in neuroblastoma of the adaptor protein p140Cap, encoded by the SRCIN1 gene. Its intrinsic heterogeneity makes it difficult to successfully treat, resulting in overall survival of 50% for half of the patients. Neuroblastoma, the most common extra-cranial pediatric solid tumor, is responsible for 9–15% of all pediatric cancer deaths.

Scaffold protein