**Abbreviations**

*Pheochromocytoma, Paraganglioma and Neuroblastoma*

stratifying NB patient cohorts.

specific marker NG2 [93].

**Acknowledgements**

**Conflict of interest**

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patients, with high levels of expression positively correlating with good prognosis and high survival rate. Of note, *SRCIN1* mRNA behaves as an independent risk factor, thus providing evidence that *SRCIN1* is a useful, additional marker for better

Overall, the protein p140Cap acts as a tumor suppressor gene in NB tumors, dampening tumor volume and decreasing progression towards distant metastasis. This might occur because of an increased ability to undergo apoptosis and a decreased capability of p140Cap NB cells to proliferate *in vivo*. Tumor microenvironment could also play a role, as shown by decreased permeability of p140Cap tumor vessels, likely due to the increased presence of pericytes, as shown by their

An urgent need in NB is to increase the five-year OS rate of high-risk NB patients,

which is still less than 40% [94]. Despite emerging new therapies, the impact of treatments is very heavy for affected children, which can have serious consequences for years to come [95]. The data showing that p140Cap expressing NB have significantly increased sensitivity to low doses (10 nM concentration) of doxorubicin and etoposide, two drugs used in first line NB treatment, open new perspectives. Further, the fact that a combo treatment with Src inhibitors and low doses doxorubicin or etoposide, sensitize mock cells, reducing cell viability to that of p140Cap cells treated with chemotherapy alone, is an encouraging result. Therefore, it would be interesting to set combinatorial approaches with low doses of both chemotherapy drugs and specific inhibitors, including also the Jak2 pathway, to quantify the additional/synergistic effects. Further, to increase the understanding of the mechanism of action of p140Cap on the sensitization to specific drugs, it would be very useful to identify the vital molecular signaling mechanisms involved. To achieve these results, both automated platforms for cell viability and genome-wide CRISPR-CAS9 technology are largely available. In conclusion, we believe that these data demonstrate the potential clinical impact of SRCIN1/p140Cap expression and of p140Cap-regulated pathways in NB tumors. These results pave the way to include *SRCIN1* mRNA in the

NB patients' prognostic status, as a key marker for patient outcome.

Torino, Progetto DEFLECT to PD; Fondazione CRT 2020.1798 to PD.

There is no competing of interest to declare.

The figures and Tables have been adapted from ref. [43] Grasso et al., 2020. We give here appropriate acknowledgment to the original authors of this publication (Silvia Grasso, Melissa Alzona, Alessia Lamolinara, Andrea Saglietto, Federico Tommaso Bianchi, Sara Cabodi, Iris Chiara Salaroglio, Federica Fusella, Marzia Ognibene, Manuela Iezzi, Annalisa Pezzolo, Valeria Poli, Ferdinando Di Cunto, Alessandra Eva, Chiara Riganti, Luigi Varesio). This work was supported by AIRC (Associazione Italiana Ricerca Cancro) to PD (IG- 20107), Compagnia San Paolo,

The article Grasso et al., [43] is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution

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