Potential use of CXCL12/CXCR4 and sonic hedgehog pathways as therapeutic targets in medulloblastoma

Abstract

Medulloblastoma (MB) is the most common malignant brain tumor occurring in children, and although high long-term survival rates have been reached with current therapeutic protocols, several neurological injuries are still observed among survivors. It has been shown that the development of MB is highly dependent on the microenvironment surrounding it and that the CXCL12 chemokine and its receptor, CXCR4 and the Sonic Hedgehog (SHH) pathway are crucial for cerebellar development, coordinating proliferation and migration of embryonic cells and malfunctions in these axes can lead to MB development. Indeed, the concomitant overactivation of these axes was suggested to define a new MB molecular subgroup. New molecules are being studied, aiming to inhibit either CXCR4 or the SHH pathways and have been tested in preclinical settings for the treatment of cancers. The use of these molecules could improve MB treatment and save patients from aggressive surgery, chemotherapy and radiotherapy regimens, which are responsible for severe neurological consequences. This review aims to summarize current data about the experimental inhibition of CXCR4 and SHH pathways in MB and its potential implications in treatment of this cancer.

Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway

“…In our study, we observed that LINC01426 functioned in LUAD cells through the hedgehog pathway. Hedgehog pathway plays momentous roles in many malignant tumors, such as hepatocellular carcinoma 30 , medulloblastoma 31 , glioblastoma 32 , and pancreatic cancer 33 . Through further investigation, we found that LINC01426 knockdown inhibited the protein level of SHH but had no significant effect on its mRNA level.…”

Identification of key genes and pathways of thyroid cancer by integrated bioinformatics analysis

“…The potential use of CXCL12/CXCR4 and sonic hedgehog pathways were proven as therapeutic targets in medulloblastoma (Amarante et al, 2018). Another study showed that the long noncoding RNA LSINCT5 can promote ovarian cancer cell proliferation, migration and invasion through the CXCL12/CXCR4…”

“…The biological roles of chemokine (C‐X‐C motif) ligand 12 ( CXCL12 ) were also mostly reported in different human cancers. The potential use of CXCL12/CXCR4 and sonic hedgehog pathways were proven as therapeutic targets in medulloblastoma (Amarante et al, ). Another study showed that the long noncoding RNA LSINCT5 can promote ovarian cancer cell proliferation, migration and invasion through the CXCL12/CXCR4 signalling axis (Long et al, ).…”

Combination of PET and CXCR4-Targeted Peptide Molecule Agents for Noninvasive Tumor Monitoring

“…Such direct visualization could be used to evaluate disease markers and provide the information necessary for developing personalized treatment plans using biological target-specific therapeutic agents. CXCR4 is an important therapeutic target in many diseases and several CXCR4 antagonists are being evaluated clinically 13, 15, 20-33. Therefore, development of a noninvasive method for evaluating and monitoring biological changes in CXCR4 status is vital for both preclinical studies and ongoing clinical trials.…”