Light-Based Conquest of Pancreatic Cancer

If you’ve been diagnosed with metastatic pancreatic cancer, you’ve probably been told that you have very few options for effective treatment. The poor prognosis is made even worse if you develop resistance to the main chemotherapy drug, gemcitabine (brand name: Gemzar®). For those who find themsevles in this unfortunate situation, treatment with a drug called irinotecan (brand name: Camptosar®) can extend survival, based on findings reported at the European Society for Medical Oncology 16th World Congress on Gastrointestinal Cancer in Barcelona, Spain. A special nanoliposomal form of this drug has been approved for treatment in Europe and the United States.

The problem is that the cancer eventually develops resistance to irinotecan (and other drugs) as well. The therapeutic potential of irinotecan is hindered by several resistance mechanisms. One of these mechanisms involves a protein called ABCG2, which enables cancer cells to pump irinotecan out of the cell, thereby weakening its treatment punch. A recent study at Harvard Medical School’s Wellman Center for Photomedicine showed that photodynamic therapy (PDT) reduced the cancer cell’s expression of ABCG2, and this, in turn, was linked with increased irinotecan levels inside pancreatic cancer cells.

Going further, the researchers found that PDT blocked the expression of survivin, another protein involved in treatment resistance. Thus, PDT clearly enhanced the treatment potential of irinotecan. At the same time, the Harvard team demonstrated that the “combination of single low-dose PDT and a subclinical dose of nanoliposomal irinotecan synergistically inhibited tumor growth by 70% for three weeks compared to 25% reduction after either [treatment alone],” as reported online ahead-of-print in the 15 December 2015 issue of Cancer Research.

In a separate study, the same research team showed that the nanoliposome technology enhanced the effectivenesss of a molecular targeting drug (cabozantinib, XL184). Exposing the pancreatic tumor to near-infrared light after intravenous treatment with a special liposomal preparation (containing both the XL184 agent and a photosensitizing agent) triggers photodynamic damage of tumor cells and microvessels, while simultaneously releasing the XL184 inside the tumor. A single light-based treatment led to prolonged tumor shrinkage and suppressed experimental metastases in pancreatic cancer, as reported online ahead-of-print in the 18 January 2016 issue of Nature Nanotechnology.

Light-Based Conquest of A Deadly Cancer

Taken together, the Harvard findings offer new opportunities for clinical testing and eventual implementation as an integrative approach—that is, combining PDT with various anticancer drugs for a more humane and effective treatment of pancreatic cancer. These days, many anticancer treatments ultimately fail against advanced cancer because the malignant cells develop resistance to the treatment. PDT may be capable of minimizing and perhaps even nullifying such resistance.  In addition, other preclinical research has shown that PDT has immune-enhancing effects that could help overcome the deadly problem of metastases.

So far, the only clinical evidence showing that PDT can prolong survival for people diagnosed with inoperable pancreatic cancer comes from a small study conducted in the United Kingdom. Dr. Stephen Bown and colleagues at the National Medical Laser Centre in London were able to document that PDT did indeed break down and destroy pancreatic tumors.  Though the survival statistics were not significantly better than those of standard chemotherapy, patients treated with PDT enjoyed a good quality of life due to lack of treatment-related toxicities.  Such toxicities—and the reduced quality of life that results therefrom—are among the main reasons doctors and patients alike are searching for effective alternatives to chemotherapy.

In conclusion, the scientific evidence to date has shown that PDT significantly decreases pancreatic cancer cell growth, destroys pancreatic tumors, and prolongs the survival of patients with inoperable pancreatic cancer without adversely affecting one’s quality of life. The fact that PDT was able to overcome the resistance mechanisms for a key chemotherapy drug—one already approved for pancreatic cancer, but with limited success on a stand-alone basis—underscores the potential for integrating this powerful treatment strategy into mainstream cancer care. Since so little clinical research has evaluated the potential benefits of PDT on pancreatic cancer, clinical trials are urgently needed.

Sources

Huang HC, Mallidi S1, Liu J, Chiang CT, Mai Z, Goldschmidt R, Ebrahim-Zadeh N, Rizvi I, Hasan T. Photodynamic therapy synergizes with irinotecan to overcome compensatory mechanisms and improve treatment outcomes in pancreatic cancer. Cancer Res. 2015 Dec 30. [Epub ahead of print]

Spring BQ, Bryan Sears R, Zheng LZ, Mai Z, Watanabe R, Sherwood ME, Schoenfeld DA, Pogue BW, Pereira SP, Villa E, Hasan T. A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways. Nat Nanotechnol. 2016 Jan 18. [Epub ahead of print]

Tangutoori S, Spring BQ, Mai Z, Palanisami A, Mensah L, Hasan T. Simultaneous delivery of cytotoxic and biologic therapeutics using nanophotoactivatable liposomes enhances treatment efficacy in a mouse model of pancreatic cancer. Nanomedicine. 2015 Sep 25. [Epub ahead of print]

Huggett MT, Jermyn M, Gillams A, Illing R, Mosse S, Novelli M, Kent E, Bown SG, Hasan T, Pogue BW, Pereira SP. Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer. Br J Cancer. 2014 Apr 2;110(7):1698-704

Bown SG, Rogowska AZ, Whitelaw DE, Lees WR, Lovat LB, Ripley P, Jones L, Wyld P, Gillams A, Hatfield AW. Photodynamic therapy for cancer of the pancreas. Gut. 2002;50 (4:549–557.

Ayaru L, Bown SG, Pereira SP. Photodynamic therapy for pancreatic carcinoma: experimental and clinical studies. Photodiagnosis Photodyn Ther. 2004 Sep;1(2):145-55.