CXCR4 and CCR7: Two eligible targets in targeted cancer therapy

Abstract

Cancer is one of the most common cause of death in the world with high negative emotional, economic, and social impacts. Conventional therapeutic methods, including chemotherapy and radiotherapy, have not proven satisfactory and relapse is common in most cases. Recent studies have focused on targeted therapy with more precise identification and targeted attacks to the cancer cells. For this purpose, chemokine receptors are proper targets and among them, CXCR4 and CCR7, with a crucial role in cancer metastasis, are being considered as desired candidates for investigation. In this review paper, the most important experimental results are highlighted on the potential targeted therapies based on CXCR4 and CCR7 chemokine receptors.

Inhibition of CXCL12/CXCR4 axis as a potential targeted therapy of advanced gastric carcinoma

“…Up to now, there have been rare studies or trials focused on the therapeutic efficacy of CXCR4 inhibitors in GC . However, it is worth mentioning that there are similar findings about the roles of CXCL12/CXCR4 axis and its inhibitors in GC as in many other solid carcinomas.…”

“…Many chemical or biological inhibitors including small molecular compounds, peptides, and antibodies have been established with roles in suppressing the expression, binding, and downstream signaling of CXC12/CXCR4 axis . Most of them are primarily used in the therapy of human immunodeficiency virus (HIV) infection or the mobilization and collection of CD34‐positive hematopoietic stem cells (HSCs) for transplantation in patients with non‐Hodgkin's lymphoma (NHL) or multiple myeloma (MM) .…”

“…CXCL12 and CXCR4 are always expressed at significantly increased levels in gastrointestinal cancers, which is associated with the activation of downstream pathways and survival, proliferation, angiogenesis, and migration of tumor cells . Furthermore, small molecular compounds, peptide antagonists, and specific antibodies against CXCR4 can efficiently inhibit downstream signaling of CXCL12/CXCR4 axis, block cancer dissemination and improve the outcome of patients .…”

BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

“…BACH1 has been placed downstream of the Raf kinase inhibitory protein, a tumor suppressor gene shown to inhibit invasion and bone metastasis in a breast cancer xenograft mouse model (Yun et al, 2011;Lee et al, 2013). Inactivation of Raf kinase inhibitory protein during tumor expansion results in higher expression of BACH1 and its target genes C-X-C chemokine receptor type 4 (CXCR-4) and matrix metal-loproteinase1 (MMP1), established drivers of tumor progression and metastasis (Foley & Kuliopulos, 2014;Mishan et al, 2016). Furthermore, ablation of BACH1 in human colon carcinoma (Davudian et al, 2016b) or in prostate cancer cells (Shajari et al, 2018) prevents cell growth, migration, and invasion in vitro, decreasing the expression of its main metastasisrelated genes, MMP1, let-7a, and CXCR4.…”

BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

“…Lee et al, 2013;Yun et al, 2011). Inactivation of RKIP during tumor expansion results in higher expression of BACH1 and its target genes C-X-C chemokine receptor type 4 (CXCR-4) and matrix metalloproteinase1 (MMP1), established drivers of tumor progression and metastasis (Foley & Kuliopulos, 2014;Mishan, Ahmadiankia, & Bahrami, 2016). Furthermore, ablation of BACH1 in human colon carcinoma (Davudian, Shajari, et al, 2016) or in prostate cancer cells (Shajari et al, 2018), prevents cell growth, migration and invasion in vitro, decreasing the expression of its main metastasis-related genes, MMP1, let-7a and CXCR4.…”