Not all cancers use CCR five to their advantage.

Not all cancers use CCR five to their advantage. I seem to remember OHM mentioning 23 cancers years ago. Chemo should be taken care of the cancer cells with LL on board . GROK had this to say:

The exact number of cancers that express the CCR5 receptor and use it to their advantage is not precisely quantified in available data, as it varies by cancer type, subtype, and study. However, CCR5 expression has been documented in a broad range of cancers, particularly those with aggressive, metastatic, or therapy-resistant features. Below is a summary based on current knowledge:
Cancers Known to Express CCR5 and Exploit It
CCR5, a G-protein-coupled chemokine receptor, is ectopically expressed in cancer cells (not typically expressed in normal epithelial cells) and is implicated in tumor progression, metastasis, immune evasion, and therapy resistance. The following cancers have been associated with CCR5 expression and its advantageous use by tumor cells:
1. Breast Cancer:
• Particularly in triple-negative breast cancer (TNBC), where >95% of tumors express CCR5.
• CCR5 promotes metastasis, cancer stem cell expansion, and resistance to DNA-damaging therapies by enhancing DNA repair pathways.
• Approximately 50% of all breast cancers express CCR5, with higher expression in basal and HER2 subtypes.
2. Prostate Cancer:
• CCR5 is expressed in a subset of prostate cancer cells, especially those with metastatic potential.
• It drives invasion, migration, and metastasis, with antagonists like anibamine reducing tumor growth and adhesion.
3. Colorectal Cancer:
• CCR5 expression is linked to metastatic colorectal cancer, where it facilitates tumor cell migration and immune cell infiltration.
• Antagonists like maraviroc have shown promise in reducing metastasis in clinical trials.
4. Pancreatic Cancer:
• CCR5 and its ligand CCL5 are highly expressed in pancreatic adenocarcinoma, promoting invasion and metastasis.
• Inhibitors like TAK-779 reduce regulatory T cell infiltration and tumor growth in mouse models.
5. Glioblastoma:
• CCR5 is highly expressed and associated with poor prognosis. It drives tumor heterogeneity, cancer stem cell formation, and invasion.
• The CCL5/CCR5 axis supports interactions with immune and stromal cells, enhancing tumor growth.
6. Melanoma:
• High CCR5 expression enhances epithelial-mesenchymal transition (EMT) and metastasis via TGFβ1 signaling.
7. Hodgkin Lymphoma:
• CCR5 antagonism by maraviroc inhibits tumor microenvironment interactions and xenograft growth.
8. Head and Neck Squamous Cell Carcinoma:
• CCR5 expression is associated with tumor progression and metastasis.
9. Gastric Cancer:
• The CCL5/CCR5 axis promotes tumor progression, with inhibition reducing cancer cell growth.
10. Esophageal Squamous Cell Carcinoma:
• Autocrine CCL5 signaling via CCR5 enhances tumor progression in vitro.
11. Ovarian Cancer:
• CCR5 expression in cancer stem cell-like populations promotes EMT and metastasis.
12. Lung Cancer:
• CCR5 is expressed in some lung cancer types, contributing to tumor progression and immune modulation.
13. Cholangiocarcinoma:
• CCR5 expression supports tumor growth and metastasis.
14. Osteosarcoma:
• CCR5 is implicated in tumor progression and metastatic behavior.
15. Pituitary Cancer:
• Limited data suggest CCR5 expression may contribute to tumor growth.
16. Thyroid Cancer:
• CCR5 expression is linked to tumor progression in some cases.
17. Acute Lymphocytic Leukemia:
• CCR5 overexpression is noted, potentially aiding tumor cell survival and infiltration.
Mechanisms of Advantage
CCR5 expression provides cancers with several advantages:
• Metastasis and Migration: CCR5 activation by ligands like CCL5 (RANTES) promotes cancer cell migration and homing to metastatic sites (e.g., bone, lung).
• Cancer Stem Cell Expansion: CCR5 enhances “stemness,” contributing to therapy resistance and tumor recurrence.
• DNA Damage Repair: CCR5 upregulates DNA repair pathways (e.g., Fanconi anemia, homologous recombination repair), reducing the efficacy of chemotherapy and radiotherapy.
• Immune Evasion: CCR5 recruits regulatory T cells (Tregs) and tumor-associated macrophages, creating an immunosuppressive tumor microenvironment.
• Angiogenesis: CCR5 supports endothelial progenitor cell-mediated angiogenesis, aiding tumor growth.
Prevalence and Variability
• Prevalence: CCR5 is expressed in a significant proportion of tumors in the listed cancers, with some (e.g., TNBC, glioblastoma) showing near-universal expression in specific subtypes. In breast cancer, >50% of tumors are CCR5+ across 2,200+ patient samples, with TNBC at >95%.
• Variability: Expression varies by cancer subtype, stage, and patient population. For example, CCR5 is more prevalent in aggressive, metastatic, or basal-like tumors than in less aggressive subtypes (e.g., luminal A breast cancer).
• Context-Dependent Role: In some cancers (e.g., Ewing’s sarcoma, renal cancer), CCR5 expression may correlate with better prognosis due to enhanced CD8+ T cell infiltration, but this is less common.
Therapeutic Implications
The widespread expression of CCR5 in cancers has led to clinical trials targeting it with antagonists originally developed for HIV, such as:
• Maraviroc: A small-molecule CCR5 inhibitor showing promise in metastatic colorectal cancer and breast cancer models by reducing metastasis and tumor growth.
• Leronlimab: A humanized monoclonal antibody targeting CCR5, under investigation for metastatic TNBC.
• These inhibitors block CCR5-mediated signaling, reducing migration, metastasis, and immune suppression while enhancing sensitivity to DNA-damaging therapies.
Challenges in Quantification
• Incomplete Data: Not all cancers have been systematically studied for CCR5 expression, and some (e.g., pituitary, thyroid) have limited evidence.
• Heterogeneity: Expression levels vary within tumors and across patients, complicating precise counts.
• Ongoing Research: New studies may identify additional CCR5-expressing cancers or refine the role of CCR5 in existing ones.
Conclusion
At least 17 cancer types are documented to express CCR5 and exploit it for advantages like metastasis, therapy resistance, and immune evasion. Breast cancer (especially TNBC), prostate cancer, colorectal cancer, pancreatic cancer, and glioblastoma are among the most studied, with high CCR5 expression in aggressive subtypes. The total number may be higher as research expands, but current evidence highlights CCR5 as a critical target in a significant subset of cancers, particularly those with metastatic potential.
If you need a deeper dive into specific cancers or ongoing trials, let me know!