CCR5 connection to most common cancers A work in

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May 27, 2019 at 5:21 PM 10,304

CCR5 connection to most common cancers

A work in progress...

Most Common US Cancer Yearly Stats
https://www.cancer.gov/types/common-cancers

Good overall read
https://www.hindawi.com/journals/mi/2014/292376/
The Inflammatory Chemokine CCL5 and Cancer Progression
January 2014

1) Breast Cancer
New Cases: 271k Deaths: 42k

Feb 2019
CCR5 blockage by maraviroc: a potential therapeutic option for metastatic breast cancer.
https://www.ncbi.nlm.nih.gov/pubmed/30456574

June 2018
https://breast-cancer-research.biomedcentral....018-0981-3
Simultaneous blockade of IL-6 and CCL5 signaling for synergistic inhibition of triple-negative breast cancer growth and metastasis

Jan 2018
CCR5 governs DNA damage and breast cancer stem cell expansion
http://cancerres.aacrjournals.org/content/ear...AN-17-0915
CCR5 antagonists Maraviroc and Vicriviroc dramatically enhanced cell killing mediated by DNA-damaging chemotherapeutic agents. Single cell analysis revealed CCR5 governs PI3K/Akt, ribosomal biogenesis, and cell survival signaling. As CCR5 augments DNA repair and is re-expressed selectively on cancerous but not normal breast epithelial cells, CCR5 inhibitors may enhance the tumor-specific activities of DDR-based treatments, allowing a dose reduction of standard chemotherapy and radiation.

April 2013
The CCL5/CCR5 axis promotes metastasis in basal breast cancer
https://www.tandfonline.com/doi/full/10.4161/onci.23660

Aug 2012
CCR5 Antagonist Blocks Metastasis of Basal Breast Cancer Cells
cancerres.aacrjournals.org/content/72/15/3839.short

The CCR5 antagonists maraviroc or vicriviroc, developed to block CCR5 HIV coreceptor function, reduced in vitro invasion of basal breast cancer cells without affecting cell proliferation or viability, and maraviroc decreased pulmonary metastasis in a preclinical mouse model of breast cancer.

2) Lung
New Cases: 228k Deaths: 143k

Mar 2019
CCR5 is Associated With Immune Cell Infiltration and Prognosis of Lung Cancer
https://www.jto.org/article/S1556-0864(19)30121-2/fulltext

Feb 2014
Chemokine Receptor 5 on Pulmonary Mesenchymal Cells Promotes Experimental Metastasis via the Induction of Erythroid Differentiation Regulator 1
http://mcr.aacrjournals.org/content/12/2/274

Dec 2012
Deficiency of C–C chemokine receptor 5 suppresses tumor development via inactivation of NF–ĸB and inhibition of monocyte chemoattractant protein-1 in urethane-induced lung tumor model
https://academic.oup.com/carcin/article/33/12/2520/2464119

It was found that a CCR5 inhibitor (TAK-779) reduced regulatory T cells migration to tumors so that tumor growth was smaller than in non-treated control mice

3) Prostate
New Cases: 175k Deaths: 32k

Sept 2005
Expression of CCL5 (RANTES) and CCR5 in prostate cancer
https://onlinelibrary.wiley.com/doi/pdf/10.1002/pros.20306

the CCR5 antagonist TAK779 inhibited CCL5 induced proliferation.

4)Colorectal
New Cases: 146k Deaths: 51k

March 2019
Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression via CCR5
https://www.nature.com/articles/s41419-019-1508-2
Notably, the CCR5 inhibitor, maraviroc, significantly abolished the MSC-induced tumor growth in vivo. In human clinical specimens (n=89), 20 cases (29%) were high for CCR5, whereas 69 cases (71%) were low

the 5 year survival rate for stage III, IV for colorectal cancer with low ccr5 expression was 70% and the high ccr5 expression just 10%, p value .001.

April 2010
Low expression of chemokine receptor CCR5 in human colorectal cancer correlates with lymphatic dissemination and reduced CD8+ T-cell infiltration
https://link.springer.com/article/10.1007%2Fs...009-0868-y

5) Melanoma
New Cases: 96k Deaths: 7k
Feb 2007
Profiles of chemokine receptors in melanocytic lesions: de novo expression of CXCR6 in melanoma.
https://www.ncbi.nlm.nih.gov/pubmed/17306330
CCR5 was exclusively expressed in primary melanomas and some cutaneous metastases.

2003
Host absence of CCR5 potentiates dendritic cell vaccination.
https://www.ncbi.nlm.nih.gov/pubmed/12682253
we used a murine melanoma system and knockout mice to investigate the function of the chemokine receptor CCR5 and its ligands, CCR ligand (CCL)3 and CCL5. We found that the lack of CCR5 in the host mouse resulted in delayed tumor growth, but this effect was overcome at a higher tumor load.

6) Bladder
New Cases: 80k Deaths: 18k

7)Non-Hodgkin Lymphoma
New Cases: 74k Deaths: 20k

March 2018
High expression of CC chemokine receptor 5 (CCR5) promotes disease progression in patients with B-cell non-Hodgkin lymphomas
https://www.sciencedirect.com/science/article...via%3Dihub

Kidney Cancer
New Cases: 74k Deaths: 15k

Mar 2015
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467270/
Expression of CC chemokine receptor 5 in clear cell renal cell carcinoma and its clinical significance

9) Endometrial
New Cases: 62k Deaths: 12k

10)Leukemia
New Cases: 62k Deaths: 23k

11) Pancreatic
New Cases: 57k Deaths: 46k
Feb 2009
https://www.ncbi.nlm.nih.gov/pubmed/19155524
Disruption of CCR5-dependent homing of regulatory T cells inhibits tumor growth in a murine model of pancreatic cancer.

Selective targeting of CCR5/CCL5 signaling may represent a novel immunomodulatory strategy for the treatment of cancer.
we have found that the growth of pancreatic adenocarcinoma may be inhibited by CCR5-mediated blockade of Treg migration.

12) Thyroid
New Cases: 52k Deaths: 2k

13) Liver
New Cases: 42k Deaths: 31k

Gastic Cancer
New Cases: 27k Deaths: 11k
Feb 2008
https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.23401
Gastric cancer cells exploit CD4+ cell derived CCL5 for their growth and prevention of CD8+ cell involved tumor elimination

They did mouse models also with antagonist, 6 week all the mice died without the antagonist, 95% lived with.

Hodgkin Lymphoma
New Cases: 8k Deaths: 1k
Mar 2019
CCR5 antagonism by maraviroc inhibits Hodgkin lymphoma microenvironment interactions and xenograft growth
http://www.haematologica.org/content/104/3/564

Oct 2007
Expression of CCR5 receptors on Reed–Sternberg cells and Hodgkin lymphoma cell lines: Involvement of CCL5/Rantes in tumor cell growth and microenvironmental interactions
https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.23119

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