Springer Science and Business Media LLC

T regulatory cells, a subset of T lymphocytes, function to suppress immune responses. FOXP3, a member of the forkhead family of transcription factors, is a good marker for T regulatory cells. Since sentinel nodes are important sites of immunomodulation in breast cancer, we studied the association between T regulatory cells and nodal metastasis using FOXP3 expression in sentinel nodes with and without metastatic breast carcinoma. Following sample size calculations, we selected 140 sentinel nodes from breast cancer patients; 70 with metastasis (sentinel node+) and 70 without metastasis (sentinel node–). FOXP3 expression in sentinel nodes was studied by immunohistochemistry. Cortical cells expressing FOXP3 were counted in 10 high power fields. In the evaluable cases, the node positive (n = 66) and negative (n = 69) groups were well balanced for all clinicopathological parameters except histological type. The mean number of T regulatory cells expressing FOXP3 (per 10 hpf) was 139 in the node positive and 132 in the node negative group (P = 0.540). The mean number of T regulatory cells was 162 in patients ≤35 years of age (n = 8) compared to 133 in older patients (P = 0.250). Primary tumor pathological characteristics like tumor type, grade, size, and ER, PR, and HER2 status did not correlate with FOXP3 expression. The number of FOXP3-expressing T regulatory cells does not differ significantly between sentinel node+ and sentinel node– samples. It was also not affected by primary tumor characteristics like tumor type, grade, size, hormone receptor, and HER2 status.

Protein kinase CK2 inhibition has long been considered as an attractive anti-cancer strategy based on the following considerations: CK2 is a pro-survival kinase, it is frequently over-expressed in human tumours and its over-expression correlates with a worse prognosis. Preclinical evidence strongly supports the feasibility of this target and, although dozens of CK2 inhibitors have been described in the literature so far, CX-4945 (silmitasertib) was the first that entered into clinical trials for the treatment of both human haematological and solid tumours. However, kinase inhibitor monotherapies turned out to be effective only in a limited number of malignancies, probably due to the multifaceted causes that underlie them, supporting the emerging view that multi-targeted approaches to treat human tumours could be more effective. In this review, we will address combined anti-cancer therapeutic strategies described so far which involve the use of CX-4945. Data from preclinical studies clearly show the ability of CX-4945 to synergistically cooperate with different classes of anti-neoplastic agents, thereby contributing to an orchestrated anti-tumour action against multiple targets. Overall, these promising outcomes support the translation of CX-4945 combined therapies into clinical anti-cancer applications.

Ferroptosis, a newly form of regulated cell death (RCD), is characterized by iron dyshomeostasis and unrestricted lipid peroxidation. Emerging evidence depicts a pivotal role for ferroptosis in driving some pathological processes, especially in cancer. Triggering ferroptosis can suppress tumor growth and induce an anti-tumor immune response, denoting the therapeutic promises for targeting ferroptosis in the management of cancer. As an autophagic phenomenon, ferritinophagy is critical to induce ferroptosis by degradation of ferritin to release intracellular free iron. Recently, a great deal of effort has gone into designing and developing anti-cancer strategies based on targeting ferritinophagy to induce ferroptosis. This review delineates the regulatory mechanism of ferritinophagy firstly and summarizes the role of ferritinophagy-induced ferroptosis in cancer. Moreover, the strategies targeting ferritinophagy to induce ferroptosis are highlighted to unveil the therapeutic value of ferritinophagy as a target to manage cancer. Finally, the future research directions on how to cope with the challenges in developing ferritinophagy promoters into clinical therapeutics are discussed.