Vascular Cancer

Symptoms

Vascular tumors can occur anywhere on the body and appear as raised bumps. They may be red and look like a blood blister, or they may be the same color as the skin. Sometimes their appearance is bruised or changed in size due to bleeding.

Pathways

Improved understanding of the signaling pathways associated with vascular tumors has driven the development of molecularly targeted therapies. There are many signaling pathways involved in the pathogenesis of vascular tumors. Some major pathways related, including

• VEGF/VEGFR pathway, regulate embryonic development and angiogenesis;
• Notch pathway is a conserved ligand-receptor signaling pathway that regulates cell fate and differentiation;
• β-adrenergic signaling can regulate multiple fundamental biological processes of tumor progression and metastasis, including promotion of inflammation, angiogenesis, migration, invasion, and resistance to programmed cell death, besides, evidence shows that β-adrenergic signaling inhibits DNA damage repair and cellular immune responses.
• Tie-2 and angiopoietin (Ang) is another receptor-ligand system involved in physiological and pathogenic angiogenesis, Ang-1 is a key player in vascular maturation and mediates EC migration, adhesion, and survival;
• PI3K/AKT/mTOR is a key signaling pathway in cell growth and survival, and overactivation has been implicated in various tumor pathogenesis;
• Ras-MAPK pathway is a major driver of childhood vascular tumor tumorigenesis.

In addition, the HIF-α-mediated pathway and PDGF/PDGFR-β signaling are also involved in the occurrence and progression of vascular tumors.

Fig. 1 Ras-MAPK pathway in leading to childhood vascular tumors

Treatment

Surgery, Photocoagulation (seal off blood vessels or destroy tissue), Cryotherapy, Embolization, Chemotherapy, Sclerotherapy, Radiation therapy, Targeted therapy, and Immunotherapy are the commonly used treatment for vascular tumors.

Targeted therapy usually causes less damage to normal cells than chemotherapy or radiation therapy. Different types of targeted therapy are being used or studied including:

• Angiogenesis inhibitors: Stop cells from dividing and stop the growth of new blood vessels that tumors need to develop.
• mTOR inhibitors: block the mTOR protein, stops cancer cells from growing and prevent the formation of new blood vessels (Sirolimus).
• Kinase Inhibitors: block signals required for tumor growth, Trametinib (a reversible inhibitor of MEK 1/2) is being studied to treat epithelioid hemangioendothelioma.

Immunotherapy is a treatment that uses the patient’s immune system to fight disease. The following types of immunotherapies are being used in the treatment of vascular tumors:

Interferon: This treatment interferes with the division of tumor cells and can slow tumor growth. It may be used to treat juvenile nasopharyngeal angiofibroma, Kaposi sarcoma, and epithelioid hemangioendothelioma.

Immune checkpoint inhibitor therapy: there are two types of immune checkpoint inhibitor therapy:

• CTLA-4 inhibitor therapy: When CTLA-4 attaches to the protein called B7 on a tumor cell, it stops the T cell from killing the tumor cell. CTLA-4 inhibitors attach to CTLA-4 and allow the T cells to kill tumor cells. Ipilimumab is a type of CTLA-4 inhibitor.

Fig. 2 CTLA-4 inhibitor therapy

• PD-1 and PD-L1 inhibitor therapy: When PD-1 attaches to PD-L1, it stops the T cell from killing the tumor cell. PD-1 and PD-L1 inhibitors keep PD-1 and PD-L1 proteins from attaching to each other. This allows the T cells to kill tumor cells. Nivolumab is a type of PD-1 inhibitor being studied in the treatment of angiosarcoma of the soft tissue.