Tumor-and osteoclast-derived NRP2 in prostate cancer bone metastases

Understanding the role of neuropilin 2(NRP2)in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone metastasis.We observed a significant upregulation of NRP2 in prostate cancer cells metastasized to bone.Here,we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis,implicating NRP2 as a promising therapeutic target.Since,osteoclasts present in the tumor microenvironment express NRP2,we have investigated the potential effect of targeting NRP2 in osteoclasts.Our results revealed NRP2 negatively regulates osteoclast differentiation and function in the presence of prostate cancer cells that promotes mixed bone lesions.Our study further delineated the molecular mechanisms by which NRP2 regulates osteoclast function.Interestingly,depletion of NRP2 in osteoclasts in vivo showed a decrease in the overall prostate tumor burden in the bone.These results therefore indicate that targeting NRP2 in prostate cancer cells as well as in the osteoclastic compartment can be beneficial in the treatment of prostate cancer bone metastasis.

Correction: Tumor microenvironment: an evil nexus promoting aggressive head and neck squamous cell carcinoma and avenue for targeted therapy

Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-020-00419-w,published online 12 January 2021 After online publication of the article1,the authors noticed an error in affiliation of co-authors Dr.Nissar A.Wani.Dr.Wani is erroneously linked to Sidra Medicine,Doha,Qatar who is actually working at the Department of Biotechnology,School of Life Sciences,Central University of Kashmir,Ganderbal,Jammu&Kashmir,India.Also,the department name"Cancer Research Department"for the first author Ajaz A.Bhat is missing.

Tumor microenvironment: an evil nexus promoting aggressive head and neck squamous cell carcinoma and avenue for targeted therapy

Head and neck squamous cell carcinoma(HNSCC)is a very aggressive disease with a poor prognosis for advanced-stage tumors.Recent clinical,genomic,and cellular studies have revealed the highly heterogeneous and immunosuppressive nature of HNSCC.Despite signifcant advances in multimodal therapeutic interventions,failure to cure and recurrence are common and account for most deaths.It is becoming increasingly apparent that tumor microenvironment(TME)plays a critical role in HNSCC tumorigenesis,promotes the evolution of aggressive tumors and resistance to therapy,and thereby adversely affects the prognosis.A complete understanding of the TME factors,together with the highly complex tumor-stromal interactions,can lead to new therapeutic interventions in HNSCC.Interestingly,different molecular and immune landscapes between HPV^(+ve) and HPV^(-ve)(human papillomavirus)HNSCC tumors offer new opportunities for developing individualized,targeted chemoimmunotherapy(CIT)regimen.This review highlights the current understanding of the complexity between HPV^(+ve) and HPV^(-ve) HNSCC TME and various tumor-stromal cross-talk modulating processes,including epithelial-mesenchymal transition(EMT),anoikis resistance,angiogenesis,immune surveillance,metastatic niche,therapeutic resistance,and development of an aggressive tumor phenotype.Furthermore,we summarize the recent developments and the rationale behind CIT strategies and their clinical applications in HPV^(+ve) and HPV^(-ve) HNSCC.