Years ago, when I was just starting my healthcare career, I worked with a team specializing in the management of patients with pancreatic cancer. Despite the dedication and compassion of our team, revolutionary surgical techniques, and top-notch palliative care, all too often our patients died. Even today, some 30 years later, pancreatic cancer has a poor prognosis. It’s seldom detected in its early stages, and often spreads rapidly. Signs and symptoms frequently don’t appear until the disease is advanced and surgical removal isn’t possible.
Pancreatic cancer touches so many people. It killed my childhood mentor and one of my best friends. It’s taken the lives of many household names, from astronauts to actors, entrepreneurs to opera singers. For example, Patrick Swayze, Randy Pausch, Luciano Pavarotti, Dizzy Gillespie, Count Basie, Michael Landon, Joan Crawford, Sally Ride and of course, Apple CEO – Steve Jobs.
So, I was excited to hear about new research into a targeted anti-cancer therapy that promised limited side effects. The study, published April 22 in the Proceedings of the National Academy of Sciences found that treating mice with an attenuated, radioactively labeled bacteria – Listeria monocytogenes – drastically reduced the number of metastases, while leaving normal tissue unscathed.
The notion of using bacteria to attack tumors is not new. Robert Hoffman, a cancer biologist at the University of California, San Diego, who was not involved in the current study, has shown that Salmonella can kill mouse cancer cells, including metastases of pancreatic cancer.
Other research has shown that a Listeria strain known as CRS-207 has the ability to stimulate an immune response in Phase 1 and 2 trials.
In the new study, researchers at Albert Einstein College of Medicine have paired this technique with a radioactive isotope to selectively kill tumor cells, focusing on the metastatic cells that so often elude current treatment regimens.
It’s this combination of approaches that synergistically target metastases, that’s new. Claudia Gravekamp, an immunologist at Albert Einstein College of Medicine who led the study with nuclear medicine researcher Ekaterina Dadachova had previously demonstrated that an attenuated strain of Listeria monocytogenes, a type of bacterium that penetrates host cells during infection, selectively killed breast cancer cells without damaging normal tissue. The bacteria’s ability to target only diseased cells raised the possibility that it could be used to treat metastatic cancer by both directly killing cells and by carrying anti-tumor therapies—like radiation—to cancer cells.
Gravekamp and Dadachova tested the bacteria against highly metastatic pancreatic cancer in mice. First, they demonstrated that the bacteria proliferated well in the animals’ metastases, but poorly in the primary tumor, and not at all in normal tissues like spleen, suggesting the bacteria would be good candidates for delivering a therapy to far-flung metastases.
Then, the researchers armed the Listeria with the Rhenium-188, a radionuclide that kills cells by releasing DNA-damaging. Sure enough, regular injections of the Rhenium-188 labeled bacteria decreased metastases by 90% versus controls.
While this implies that bacteria have to potential to be used to deliver therapeutic radiation doses to metastases, the bacteria were administered before metastases were established, notes Donald Buchsbaum, a radiation biologist at the University of Alabama at Birmingham who was not involved in the study. “So to some extent it’s a prevention model.”
Future work will need to focus on targeting established metastases, possibly by exploring other radioisotope options. Gravekamp and Dadachova are currently refining their protocol and examining alternative radioisotopes to achieve a 100% reduction of metastases, but have high hopes for their bacteria.
Though primary tumors are often removed surgically, even small pieces left behind can produce new metastases. It might be possible that one day radioactive Listeria could be part of an “early second-line treatment after surgery to prevent further metastases,” says Gravekamp.
Which is great news in the war against cancer and not a bad deal for the Listeria bacteria which normally gets a bad rap for causing the infection listeriosis – the leading cause of death among food-borne bacterial pathogens – responsible for approximately 2,500 illnesses and 500 fatalities annually in the United States.