Macrophages: Key Players in the Battle against Triple-Negative Breast Cancer
Abstract
:1. Introduction
2. Concept of Breast Cancer
2.1. Pathological and Molecular Characterization of TNBC
2.2. Prevalence, Epidemiology, and Risk Factors
2.3. Prognostic Factors
2.4. Conventional Approaches in Diagnosis and Treatment
2.5. Modern Approach to TNBC Treatment
3. Tumor-Associated Macrophages in TNBC
3.1. Crosstalk between Tumor-Associated Macrophages and Triple-Negative Breast Cancer
3.2. Regulation of PD-1 Expression by TAMs
3.3. Targeting Tumor-Associated Macrophages in Triple-Negative Breast Cancer
3.3.1. Inhibition of Macrophage Recruitment to the Tumor
3.3.2. Direct Elimination of TAMs
3.3.3. Reprogramming TAMs into Anti-Tumor Macrophages
3.3.4. Activation of Macrophage Phagocytosis
3.4. Potential Challenges of TAM-Targeted Therapies
3.5. Future Perspectives: Clinical Trials Targeting Immune Checkpoints and Other Strategies in TNBC
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Drugs for Inhibition of Macrophage Recruitment to the Tumor | ||||
---|---|---|---|---|
Drug | Mechanism of Action | Other Drugs/Interventions Used in Trial | ClinicalTrials.gov ID | Phase |
Trabectedin | Alkylating agent suppressing monocyte recruitment | Dexamethasone | NCT00580112 | Phase II; completed |
Dexamethasone | NCT00050427 | Phase II; completed | ||
Lacnotuzumab (MSC110) | Monoclonal antibody against CSF-1 | PDR001 | NCT02807844 | Phase Ib/II; completed |
Carboplatin, gemcitabine | NCT02435680 | Phase II; completed | ||
PLX3397 | CSF-1/CSF-1R inhibitor | Eribulin | NCT01596751 | Phase Ib/II; completed |
Multiple drugs | NCT01042379 | Phase II; recruiting | ||
LY3022855 | CSF-1/CSF-1R inhibitor | - | NCT02265536 | Phase I; completed |
Cabiralizumab | CSF-1/CSF-1R inhibitor | Nivolumab, carboplatin, paclitaxel | NCT04331067 | Phase Ib/II; active, not recruiting |
Drugs for direct elimination of TAMs | ||||
Drug | Mechanism of action | Other drugs/interventions used in trial | ClinicalTrials.gov ID | Phase |
Clodronate | Bisphosphonate selectively killing macrophages. | Placebo | NCT00009945 | Phase III; completed |
Ibandronate, zoledronic acid | NCT00127205 | Phase III; completed | ||
Zoledronic acid | Bisphosphonate depleting TAMs and inhibiting angiogenesis | Atorvastatin, standard neoadjuvant chemotherapy | NCT03358017 | Phase II; completed |
- | NCT04045522 | Unknown status | ||
- | NCT02595138 | Phase III; unknown status | ||
Drugs for reprogramming TAMs into anti-tumor macrophages | ||||
Drug | Mechanism of action | Other drugs/interventions used in trial | ClinicalTrials.gov ID | Phase |
Alpelisib | PI3Kα-specific inhibitor promoting M1-like phenotype | Nab-paclitaxel | NCT04251533 | Phase III; active, not recruiting |
Nab-paclitaxel, iNOS inhibitor | NCT05660083 | Phase II; recruiting | ||
Enzalutamide | NCT03207529 | Phase I; completed | ||
Pembrolizumab | PD-1 inhibitor used in combination therapy | Lenvatinib | NCT04427293 | Phase I; recruiting |
Intraoperative radiation therapy | NCT02977468 | Phase I; recruiting | ||
Olinvacimab | NCT04986852 | Phase II; recruiting | ||
Capivasertib (AZD5153) | BRD4 inhibitor promoting M1 polarization | Fulvestrant | NCT01226316 | Phase I; active, not recruiting |
Paclitaxel | NCT02423603 | Phase II; active, not recruiting | ||
Enzalutamide, Fulvestrant | NCT03310541 | Phase I; completed | ||
Metformin | Agent used to inhibit M2 polarization and decrease tumor size | Night fasting | NCT05023967 | Phase IIb; recruiting |
Doxycycline | NCT02874430 | Phase II; active, not recruiting | ||
Calorie restriction | NCT04248998 | Phase II; active, not recruiting | ||
Drugs for activation of macrophage phagocytosis | ||||
Drug | Mechanism of action | Other drugs/interventions used in trial | ClinicalTrials.gov ID | Phase and stage |
IMM2520 | Anti-CD47 and PD-L1 bispecific antibody | - | NCT05780307 | Phase I; recruiting |
Evorpacept (ALX148) | CD47-SIRPα inhibitor improving macrophage phagocytosis | Fam-Trastuzumab Deruxtecan-Nxki | NCT05868226 | Phase I/Ib; recruiting |
Hu5F9-G4 | Anti-CD47 antibody for targeting cancer cells | Olaparib | NCT05807126 | Phase I; withdrawn |
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Padzińska-Pruszyńska, I.; Kucharzewska, P.; Matejuk, A.; Górczak, M.; Kubiak, M.; Taciak, B.; Król, M. Macrophages: Key Players in the Battle against Triple-Negative Breast Cancer. Int. J. Mol. Sci. 2024, 25, 10781. https://doi.org/10.3390/ijms251910781
Padzińska-Pruszyńska I, Kucharzewska P, Matejuk A, Górczak M, Kubiak M, Taciak B, Król M. Macrophages: Key Players in the Battle against Triple-Negative Breast Cancer. International Journal of Molecular Sciences. 2024; 25(19):10781. https://doi.org/10.3390/ijms251910781
Chicago/Turabian StylePadzińska-Pruszyńska, Irena, Paulina Kucharzewska, Agata Matejuk, Małgorzata Górczak, Małgorzata Kubiak, Bartłomiej Taciak, and Magdalena Król. 2024. "Macrophages: Key Players in the Battle against Triple-Negative Breast Cancer" International Journal of Molecular Sciences 25, no. 19: 10781. https://doi.org/10.3390/ijms251910781