The End of Pancreatic Cancer Could Be Just Around the Corner

Patients have a 1.7% chance of being diagnosed with pancreatic cancer in their lifetime, which is a relatively small number. But to some 64,000 Americans who will be diagnosed with the disease this year, and the families of the 50,550 more who will die from it, the number isn’t small enough.¹

Problematically, there are no telltale symptoms of pancreatic cancer, such as unusual lumps, lesions, or swelling common to other types of cancer, that would present clearly to the patient and warrant a trip to a physician, so most patients are diagnosed late. In fact, roughly 80% of pancreatic cancer diagnoses come after the disease has already spread and is more difficult to treat.²

That’s why my team at the Fox Chase Cancer Center is working with an AI company on preclinical and clinical trials to develop a treatment that works at every stage of the disease. Hopefully, we can finally put an end to pancreatic cancer.

Why the Current Options for Pancreatic Cancer Treatment Don’t Work

Pancreatic cancer begins in the tissues of the pancreas and grows and spreads rapidly. Patients whose cancer is diagnosed before it has spread into nearby tissues and lymph nodes have the greatest chance for a cure through complete surgical removal of their tumors. But this is the case for fewer than 20% of patients, and their 5-year survival rate is only around 44%.^2,3

Pancreatic cancer begins in the tissues of the pancreas and grows and spreads rapidly. Image Credit: © LASZLO - stock.adobe.com

For the other 80% of patients, radiation, chemotherapy, and immunotherapy—a treatment that activates the immune system against cancer cells—are the primary forms of treatment. Chemotherapy alone does not work for all patients because most pancreatic adenocarcinomas are surrounded by dense stroma, or tissue, which prevents treatment from reaching the tumors. When combined with new immunotherapy treatments, chemotherapy is much more likely to be successful. Yet, even with currently available medical advancements, no significant improvements have occurred in patient outcomes in more than a decade. The 5-year survival rate for patients whose cancer has spread into surrounding tissues and organs is 15%, and for the more than 50% of pancreatic cancer patients whose cancer has metastasized, the chances of surviving 5 years sharply decreases to 3%.³

A Potential End to Pancreatic Cancer

In 2020, a team of researchers at Fox Chase Cancer Center—a leading research center for pancreatic cancers based in Philadelphia—worked on preclinical testing to figure out whether LP-184 (Lantern Pharma), a new anti-cancer treatment, could specifically target a molecularly-defined subtype of pancreatic cancers, making it more effective.⁴

By the end of 2023, the preclinical data showed that LP-184—an alkylating agent that specifically targets and damages the DNA in cancer cells that carry certain biomarkers—shrunk tumors in vivo by more than 90% in just 8 weeks. Additionally, the data showed that pancreatic tumors with DNA-damage repair deficiencies were remarkably more sensitive to LP-184 than tumors without such mutations. The genetic experiments thus far have validated the role of an enzyme called prostaglandin reductase in making pancreatic tumors more responsive to LP-184. Supported by extensive preclinical data, the research team is now poised to pursue human clinical trials.⁵ The FDA has also recognized the drug’s potential and granted LP-184 orphan drug designation, which supports drugs in development for areas of great unmet need.

Because of its benefit in targeting DNA-damage repair deficiencies in solid tumors, LP-184 is also being clinically tested in patients with glioblastoma, atypical teratoid rhabdoid tumor, bladder, lung, and pediatric cancers. Earlier this year, a phase 1a clinical trial was launched to evaluate the safety and efficacy of the treatment in patients with advanced solid tumors. The team also plans on exploring potential combinations of LP-184 with standard of care chemotherapy and other agents to increase the effectiveness of treatment for pancreatic cancer. Set to conclude in the first half of 2024, the phase 1a clinical trial will pave the road for additional clinical trials across multiple diseases. Ultimately that road could lead to the end of pancreatic cancer, and a host of other cancers along with it.

About the Author

Igor Astsaturov, MD, PhD, holds the Paul F. Engstrom professorship in oncology at Fox Chase Cancer Center, Temple University Health System, in Philadelphia, Pennsylvania.

References

1. Key Statistics for Pancreatic Cancer. American Cancer Society. Last updated January 12, 2023.Accessed December 18, 2023.https://www.cancer.org/cancer/types/pancreatic-cancer/about/key-statistics.html
2. Puckett Y, Garfield K. Pancreatic Cancer. In: StatPearls. Treasure Island (FL): StatPearls Publishing; September 26, 2022. Accessed December 18, 2023. https://pubmed.ncbi.nlm.nih.gov/30085538/
3. Pancreatic Cancer: Statistics. Cancer.net. March 2023. Accessed December 18, 2023. https://www.cancer.net/cancer-types/pancreatic-cancer/statistics
4. Restifo D, McDermott JR, Cvetkovic D, et al. Conditional Dependency of LP-184 on Prostaglandin Reductase 1 is Synthetic Lethal in Pancreatic Cancers with DNA Damage Repair Deficiencies. Mol Cancer Ther. 2023;22(10):1182-1190. doi:10.1158/1535-7163.MCT-22-0818
5. Lantern Pharma Announces Significant Positive Preclinical Data in Pancreatic Cancer With Drug Candidate LP-184. Dallas, Texas: Lantern Pharma; July 20, 2021. https://www.prnewswire.com/news-releases/lantern-pharma-announces-significant-positive-preclinical-data-in-pancreatic-cancer-with-drug-candidate-lp-184-301337294.html