CRISPR-Based Therapy to Reduce MUC16 Expression in PDAC Patients
DOI:
https://doi.org/10.58445/rars.3626Keywords:
Pancreatic Ductal Adenocarcinoma (PDAC), Pancreatic Cancer, CRISPRAbstract
Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest survival rates among all cancer types, with an overall five-year relative survival rate of less than 5%. One of the causes stems from overexpression of the MUC16 gene, observed in about 20% of PDAC tumors. MUC16 is a large glycoprotein that forms a protective barrier around various epithelial cells and regulates processes such as cell proliferation and apoptosis resistance. When overexpressed, it enables cancer cells to evade immune detection, promoting metastasis. Some of the current treatment methods for PDAC include combinations of surgery, chemotherapy, radiation, targeted therapy, and immunotherapy. However, MUC16 overexpression causes resistance to chemotherapy and other treatment options, highlighting a need for alternative therapeutic strategies. Among various emerging approaches, CRISPR has gained attention as a novel gene editing tool that enables the precise modifications of DNA and holds potential to drastically improve cancer treatment. In this review, we discuss the use of CRISPR as a treatment strategy to reduce the expression of MUC16 in PDAC patients, exploring its potential to overcome therapy resistance and suppress metastasis.
References
References
American Cancer Society. (n.d.). Pancreatic cancer treatment (PDQ®) – patient version. National Cancer Institute. https://www.cancer.gov/types/pancreatic/patient/pancreatic-treatment-pdq
Bengtsson, A., Andersson, R., & Ansari, D. (2020). The actual 5-year survivors of pancreatic ductal adenocarcinoma based on real-world data. Scientific Reports, 10, Article 16425. https://doi.org/10.1038/s41598-020-73525-y
Cancer Research Institute. (2020, September 30). CRISPR: A new tool in cancer research and treatment. National Cancer Institute. https://www.cancer.gov/news-events/cancer-currents-blog/2020/crispr-cancer-research-treatment
Lin, H. K., Blake, D. A., Liu, T., Freeman, R., Lesinski, G. B., Yang, L., & Rafiq, S. (2024). Muc16CD is a novel CAR T cell target antigen for the treatment of pancreatic cancer. Molecular therapy. Oncology, 32(4), 200868. https://doi.org/10.1016/j.omton.2024.200868
Chari, S. T., Kelly, K., Hollingsworth, M. A., Thayer, S. P., Ahlquist, D. A., Andersen, D. K., Batra, S. K., Brentnall, T. A., Canto, M., Cleeter, D. F., Firpo, M. A., Gambhir, S. S., Go, V. L., Hines, O. J., Kenner, B. J., Klimstra, D. S., Lerch, M. M., Levy, M. J., Li, D., … Simeone, D. M. (2015). Early detection of sporadic pancreatic cancer: Summative review. Pancreas, 44(5), 693-712. https://doi.org/10.1097/MPA.0000000000000368
Cleveland Clinic. (n.d.). Cancer survival rate: What it means for your prognosis.https://my.clevelandclinic.org/health/articles/cancer-survival-rate
Frontiers in Immunology. (2024). CRISPR-engineered CAR T cells: Advancements in precision cancer immunotherapy. Frontiers in Immunology, 15, 1354825. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1354825/full
Haider, S., & Mussolino, C. (2025). Fine-Tuning Homology-Directed Repair (HDR) for Precision Genome Editing: Current Strategies and Future Directions. International journal of molecular sciences, 26(9), 4067. https://doi.org/10.3390/ijms26094067
Integrated DNA Technologies. (n.d.). CRISPR delivery methods. https://www.idtdna.com/pages/technology/crispr/crispr-delivery
King, R. J., Yu, F., & Singh, P. K. (2017). Genomic alterations in mucins across cancers. Oncotarget, 8(40), 67152-67168. https://doi.org/10.18632/oncotarget.17934
Kleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., Neale, R. E., Tempero, M., Tuveson, D. A., Hruban, R. H., & Neoptolemos, J. P. (2016). Pancreatic cancer. Nature Reviews Disease Primers, 2, 16022. https://doi.org/10.1038/nrdp.2016.22
Muniyan, S., Lin, J., Thakur, A., Subramani, R., & Batra, S. K. (2016). Functional characterization of MUC16 in pancreatic cancer progression and metastasis. Oncogene, 35(38), 5172-5181. https://doi.org/10.1038/onc.2016.80
National Cancer Institute. (n.d.). Pancreatic cancer treatment (PDQ®) – patient version.https://www.cancer.gov/types/pancreatic/patient/pancreatic-treatment-pdq
Das, S., & Batra, S. K. (2015). Understanding the Unique Attributes of MUC16 (CA125): Potential Implications in Targeted Therapy. Cancer research, 75(22), 4669–4674. https://doi.org/10.1158/0008-5472.CAN-15-1050
Pannunzio, N. R., Watanabe, G., & Lieber, M. R. (2017). Nonhomologous DNA end joining for repair of DNA double-strand breaks. Journal of Biological Chemistry, 293(27), 10512-10523. https://doi.org/10.1074/jbc.TM117.000374
Siegel, R. L., Miller, K. D., & Jemal, A. (2020). Cancer statistics, 2020. CA: A Cancer Journal for Clinicians, 70(1), 7-30. https://doi.org/10.3322/caac.21590
Synthego. (n.d.). What is CRISPR and how does it work? https://www.synthego.com/learn/crispr
Synthego. (n.d.). How CRISPR is being used to fight cancer. https://www.synthego.com/crispr-cancer
U.S. National Library of Medicine. (2024). A study of 27T51 in subjects with recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer (NCT06469281). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT06469281
Guo, C., Ma, X., Gao, F., & Guo, Y. (2023). Off-target effects in CRISPR/Cas9 gene editing. Frontiers in bioengineering and biotechnology, 11, 1143157. https://doi.org/10.3389/fbioe.2023.1143157
Wang, Y., & Zhang, L. (2025). CRISPR-mediated MUC16 targeting as a potential therapeutic strategy for pancreatic ductal adenocarcinoma. Cancer Gene Therapy, 32(4), 1023-1036. https://doi.org/10.1007/s12672-025-03383-5
Muniyan, S., Haridas, D., Chugh, S., Rachagani, S., Lakshmanan, I., Gupta, S., Seshacharyulu, P., Smith, L. M., Ponnusamy, M. P., & Batra, S. K. (2016). MUC16 contributes to the metastasis of pancreatic ductal adenocarcinoma through focal adhesion mediated signaling mechanism. Genes & cancer, 7(3-4), 110–124. https://doi.org/10.18632/genesandcancer.104
Downloads
Posted
Categories
License
Copyright (c) 2026 Simran Mirchandani

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.