Next Viable Routes to Targeting Pancreatic Cancer Stemness: Learning from Clinical Setbacks
Abstract
:1. Introduction
2. CSCs in PDAC: An Evolving Model
3. The Molecular Pathways Controlling PanCSCs
4. The Major Hurdles in the Therapeutic Targeting of Pancreatic Cancer Stemness
5. Route 1: Targeting the Wnt-Related Niche of PanCSCs
6. Route 2: Targeting Pro-Stemness PSCs
7. Route 3: Targeting Cancer Stemness by Nanotherapeutics
8. Route 4: Targeting the Crosstalk between TAMs and PanCSCs
9. Route 5: Metronomic Chemotherapy to Temper Therapy-Induced Cancer Stemness
10. Potential Biomarkers to Guide Next-Generation PanCSC-Targeted Therapies
11. Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Mode of Action | Example Therapeutics | Clinical Trial Stage | Target Cancer | Clinical Trials.Gov IDs |
---|---|---|---|---|
Porcupine inhibitor | LGK974 (Novartis) | Phase 1 (with PDR001 1) | Wnt-dependent solid tumor | NCT01351103 |
RXC004 (Redx Pharma) | Phase 1/2a | Solid tumor | NCT03447470 | |
ETC-1922159 (A*STAR, Singapore) | Phase 1 | Solid tumor | NCT02521844 | |
CSF-1R inhibitor | ARRY382 (Array Biopharma) | Phase 1 | Metastatic cancer | NCT01316822 |
Phase 1–2 (with pembrolizumab) | Advanced solid tumors | NCT02880371 | ||
PLX3397 (pexidartinib; Plexxikon) | Phase 1 (with durvalumab) | Metastatic/advanced PDAC or CRC | NCT02777710 | |
Phase 1/2 (with pembrolizumab) | Melanoma and solid tumors | NCT02452424 | ||
CCR-2 inhibitor | PF04136309 (Pfizer) | Phase 1 (with FOLFIRINOX chemotherapy 2) | Borderline respectable and locally advanced PDAC | NCT01413022 |
Metronomic chemotherapy | S-1 (Taiho Pharma) | Approved for metastatic PDAC in Asia |
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Tsai, K.K.; Chan, T.-S.; Shaked, Y. Next Viable Routes to Targeting Pancreatic Cancer Stemness: Learning from Clinical Setbacks. J. Clin. Med. 2019, 8, 702. https://doi.org/10.3390/jcm8050702
Tsai KK, Chan T-S, Shaked Y. Next Viable Routes to Targeting Pancreatic Cancer Stemness: Learning from Clinical Setbacks. Journal of Clinical Medicine. 2019; 8(5):702. https://doi.org/10.3390/jcm8050702
Chicago/Turabian StyleTsai, Kelvin K., Tze-Sian Chan, and Yuval Shaked. 2019. "Next Viable Routes to Targeting Pancreatic Cancer Stemness: Learning from Clinical Setbacks" Journal of Clinical Medicine 8, no. 5: 702. https://doi.org/10.3390/jcm8050702