Role of Inter- and Peritumoral Vessels and Nerves in Tumor Dissemination and Treatment Outcome

Dear Colleagues,

The vascular and nervous systems are the conduits that enable endocrine signaling to and from cancers as well as systemic dissemination of tumor cells. Both the initiation and progression of malignant diseases are affected by systemic pathophysiological cues such as metabolic state, systemic low-grade inflammation, stress, and circadian disruption, and these cues affect the tumor through the vasculature and nerves present in its microenvironment. On the other hand, cancer is (or will become) a systemic disease. Disseminated tumor cells or tumor-derived endocrine factors cause systemic disruption of organs and tissues, a process that depends on vessels and nerve endings in the tumor microenvironment. As such, vessels and nerves orchestrate both cancer initiation and progression and are thus excellent targets for preventive and therapeutic interventions.

During the last five decades, work initiated in the lab of the late Judah Folkman on the role and therapeutic targeting of the tumor vasculature has led to a revolution in understanding cancer as a systemic disease. This work has led to the development and use of anti-angiogenic treatments for blocking tumor-induced growth of new blood vessels. These treatments have significantly improved the survival of thousands of patients worldwide and are now in routine clinical use for the treatment of different tumor types. Such drugs have, however, not exhibited the universal efficacy that was initially expected. In large, this is because the process by which tumors interact with the vasculature to drive tumor progression has proven to be more complicated than many anticipated. In particular, traditional preclinical studies in animal models of cancer have not been readily translatable to clinical applications as many of the pathophysiological disruptions found in cancer patients—including metabolic and circadian disruptions, inflammation, and stress—are often missed and therefore not taken into account when designing the studies. In addition, the complex molecular interplay within and between tumor cells, immune cells, vascular and perivascular cells, and neurons leading to patient-specific disease trajectories have only started to become elucidated.

In this Special Issue, we invite researchers in the fields of tumor vascular medicine and cancer neuroscience to present novel high-quality findings or cutting-edge, comprehensive reviews that elevate our understanding of the role of tumor vessels and nerves in cancer. This includes work on:

• Tumor angiogenesis, vascular dysfunction or metastasis;
• Tumor neoneurogenesis and the mechanisms underlying the activation and role of intra- or peritumoral nerve endings in cancer;
• Pathways adopted by cancers that are disruptive to both the vasculature and peripheral nerves such as neuro/vascular growth and patterning factors;
• The regulation of (peri)tumoral nerves by the vasculature, regulation of the (peri)tumoral vasculature by nerves, and/or the inter-regulation of these systems in the context of cancer;
• Novel mechanisms enabling therapeutic targeting of the tumor vascular and/or nervous systems, or the identification and evaluation of novel drugs that target known mechanisms with significantly increased clinical potential;
• Diagnostic principles or molecular mechanisms contributing to individual variation in pathological vessel/nerve phenotypes or anti-angiogenic/neoneurogenic treatment efficacy.

Dr. Lasse Jensen
Dr. Georgios Lolas
Guest Editors

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• Angiogenesis
• Neoneurogenesis
• Cancer
• Stress
• Anti-angiogenic treatment
• Tumor nervous systems
• Microenvironment
• Metastasis