Tumor blood vessels are a key target for cancer therapeutic management. Tumor cells secrete high levels of pro-angiogenic factors which contribute to the creation of an abnormal vascular network characterized by disorganized, immature and permeable blood vessels, resulting in poorly perfused tumors. The hypoxic microenvironment created by impaired tumor perfusion can promote the selection of more invasive and aggressive tumor cells and can also impede the tumor-killing action of immune cells. Furthermore, abnormal tumor perfusion also reduces the diffusion of chemotherapeutic drugs and radiotherapy efficiency. To fight against this defective phenotype, the normalization of the tumor vasculature has emerged as a new therapeutic strategy. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. In this review, we investigate the mechanisms involved in tumor angiogenesis and describe strategies used to achieve vascular normalization.

Tumor angiogenesis and vascular normalization: alternative therapeutic targets.

Tamoxifen for early breast cancer: An overview of the randomised trials

Ionizing radiation is a non-specific but highly effective way to kill malignant cells. However, tumor recurrence sustained by a minor fraction of surviving tumor cells is a commonplace phenomenon caused by the activation of both cancer cell intrinsic resistance mechanisms, and also extrinsic intermediaries of therapy resistance, represented by non-malignant cells and structural components of the tumor stroma. The improved accuracy offered by advanced radiotherapy (RT)-technology permits reduced volume of healthy tissue in the irradiated field, and has been triggering an increase in the prescription of high-dose oligo-fractionated regimens in the clinics. Given the remarkable clinical success of high-dose RT and the current therapeutic shift occurring in the field, in this review we revise the existing knowledge on the effects that different radiation regimens exert on the different compartments of the tumor microenvironment, and highlight the importance of anti-tumor immunity and other tumor cell extrinsic mechanisms influencing therapeutic responses to high-dose radiation.

/pdf/radiotherapy-and-the-tumor-stroma-the-importance-of-dose-and-3yhds6mnt2.pdf

Radiotherapy and the Tumor Stroma: The Importance of Dose and Fractionation

A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms.

The chemokine CXCL12 (SDF-1) and its cell surface receptor CXCR4 were first identified as regulators of lymphocyte trafficking to the bone marrow Soon after, the CXCL12/CXCR4 axis was proposed to regulate the trafficking of breast cancer cells to sites of metastasis More recently, it was established that CXCR4 plays a central role in cancer cell proliferation, invasion, and dissemination in the majority of malignant diseases The stem cell concept of cancer has revolutionized the understanding of tumorigenesis and cancer treatment A growing body of evidence indicates that a subset of cancer cells, referred to as cancer stem cells (CSCs), plays a critical role in tumor initiation, metastatic colonization, and resistance to therapy Although the signals generated by the metastatic niche that regulate CSCs are not yet fully understood, accumulating evidence suggests a key role of the CXCL12/CXCR4 axis In this review we focus on physiological functions of the CXCL12/CXCR4 signaling pathway and its role in cancer and CSCs, and we discuss the potential for targeting this pathway in cancer management

/pdf/emerging-targets-in-cancer-management-role-of-the-cxcl12-3iegqhxwj8.pdf

Emerging targets in cancer management: role of the CXCL12/CXCR4 axis

Radiotherapy is a widely used treatment option in cancer. However, recent evidence suggests that doses of ionizing radiation (IR) delivered inside the tumor target volume, during fractionated radiotherapy, can promote tumor invasion and metastasis. Furthermore, the tissues that surround the tumor area are also exposed to low doses of IR that are lower than those delivered inside the tumor mass, because external radiotherapy is delivered to the tumor through multiple radiation beams, in order to prevent damage of organs at risk. The biological effects of these low doses of IR on the healthy tissue surrounding the tumor area, and in particular on the vasculature remain largely to be determined. We found that doses of IR lower or equal to 0.8 Gy enhance endothelial cell migration without impinging on cell proliferation or survival. Moreover, we show that low-dose IR induces a rapid phosphorylation of several endothelial cell proteins, including the Vascular Endothelial Growth Factor (VEGF) Receptor-2 and induces VEGF production in hypoxia mimicking conditions. By activating the VEGF Receptor-2, low-dose IR enhances endothelial cell migration and prevents endothelial cell death promoted by an anti-angiogenic drug, bevacizumab. In addition, we observed that low-dose IR accelerates embryonic angiogenic sprouting during zebrafish development and promotes adult angiogenesis during zebrafish fin regeneration and in the murine Matrigel assay. Using murine experimental models of leukemia and orthotopic breast cancer, we show that low-dose IR promotes tumor growth and metastasis and that these effects were prevented by the administration of a VEGF receptor-tyrosine kinase inhibitor immediately before IR exposure. These findings demonstrate a new mechanism to the understanding of the potential pro-metastatic effect of IR and may provide a new rationale basis to the improvement of current radiotherapy protocols.

https://serval.unil.ch/resource/serval:BIB_14B4AEA9711E.P001/REF.pdf

Low doses of ionizing radiation promote tumor growth and metastasis by enhancing angiogenesis.

Cancer wasting and quality of life react to early individualized nutritional counselling

https://journals.viamedica.pl/rpor/article/download/73442/53532

Tamoxifen in breast cancer ipse dixit in uterine malignant mixed Müllerian tumor and sarcoma-A report of 8 cases and review of the literature.

https://journals.viamedica.pl/rpor/article/download/73262/53352

Anal canal plasmacytoma-An uncommon presentation site.

https://journals.viamedica.pl/rpor/article/download/73443/53533

Isabel Monteiro Grillo

Papers

Low doses of ionizing radiation promote tumor growth and metastasis by enhancing angiogenesis.

Cancer wasting and quality of life react to early individualized nutritional counselling

Tamoxifen in breast cancer ipse dixit in uterine malignant mixed Müllerian tumor and sarcoma-A report of 8 cases and review of the literature.

Anal canal plasmacytoma-An uncommon presentation site.

3D conformal hypofractionated radical radiotherapy in early glottic cancer