For Pancreatic Cancer Patients Like Alex Trebek, New Research Suggests Resistance to Chemotherapy Can Be Reversed & Survival Rates Improved

Understanding Pancreatic Cancer

• New research is suggesting new hope in the battle against pancreatic cancer after finding that “chemoresistance can be reversed” and survival rates can be improved through “mechanotherapeutics” [a therapeutic technique using mechanical stimuli to treat disease/injury].”
• Alex Trebek died of pancreatic cancer after a year and a half of battling pancreatic cancer, an aggressive form of cancer.  After an 18-month-long cancer battle, Patrick Swayze also passed away amid his battle with the disease.
• Pancreatic cancer is a type of cancer that forms in the pancreas. It is more challenging to treat because symptoms usually don’t present themselves until the cancer has spread or metastasized. Symptoms may include weight gain, back pain, and jaundice.
• Early-stage pancreatic cancer tumors don’t appear on imaging scans, and people typically don’t experience symptoms until the disease has progressed. The pancreas’ location in the abdomen makes it harder to find tumors.
• Treatment options for pancreatic cancer may include surgery, radiation, chemotherapy, and targeted therapy.

For anyone fighting pancreatic cancer—the disease that took the life of "Jeopardy" host Alex Trabeck at age 80 and "Dirty Dancing" star Patrick Swayze at age 53— there's added hope in the battle against this disease as new research has suggested that "chemoresistance can be reversed" and survival rates can be improved through "mechanotherapeutics" [a therapeutic technique using mechanical stimuli to treat disease/injury]." The new study, which was recently published in the journal Nature Materials and titled "Engineered matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoids," says that targeting drugs in the microenvironment around a tumor can assist in how patients react to treatment. "Our study shows the importance of the tumor microenvironment and its properties in dictating how cancer progresses and responds to drug treatment. It also demonstrates that chemoresistance can be reversed," Bauer LeSavage, PhD, who directed the study in the Bioengineering Department at Stanford University in California, said in a statement, according to Medscape Medical News . According to the American Cancer Society’s Cancer Facts & Figures 2024 , the five-year relative survival rate for pancreatic cancer [for all stages], which develops in the pancreas and is known as the "silent disease," is estimated to be 13%, a number experts with the Pancreatic Cancer Action Network (PanCAN) previously said is more than double the rate from 10 years ago, which was approximately 6%. The study authors used an engineered three-dimensional pancreas tissue with "varying degrees of stiffness and different biochemical properties" to test out with small pieces of actual tumors from pancreatic cancer patients. The researchers viewed the growth of the real tumors and then attempted to eliminate them with drugs, ultimately discovering that cancer cells growing in a stiff matrix were "more resistant" to chemo, Medscape Medical News reports. The medical news outlet explains further, "They also found that high amounts of the tissue-strengthening protein hyaluronic acid in stiff tissue seemed to signal the cancer cells to develop tiny pumps on their surface which shuttled out the drugs before they could take effect. 'When the researchers moved the cancer cells into either a softer matrix or a stiff matrix in which the hyaluronic acid receptor, called CD44, was blocked, the chemotherapy drugs started working again." Sarah Heilshorn, PhD, a senior study author and professor at Stanford stated in response to the findings, "This suggests that if we can disrupt the stiffness signaling that's happening through the CD44 receptor, we could make patients' pancreatic cancer treatable again by normal chemotherapy. "These results suggest an exciting new direction for new drug development."

Expert Resources On Pancreatic Cancer

• Detecting Pancreatic Cancer Early Is Crucial
• Immunotherapy Offers New Hope for Fighting Pancreatic Cancer
• 3 Key Pancreatic Cancer Red Flags to Look Out For; Some Were Present in Alex Trebek & Patrick Swayze
• Pancreatic Cancer Treatment Just Became a Lot More Accessible; New Platform Is Designed to Test Multiple Therapies at the Same Time
• Management of Von-Hippel Lindau Disease

LeSavage says this study puts emphasis on the importance of the extracellular matrix, which the National Cancer Institute describes as "a large network of proteins and other molecules that surround, support, and give structure to cells and tissues in the body." He believes the use of organoids , artificial three-dimensional tissue cultures derived from stem cells, can assist in testing how drugs can play a role in fighting cancers. LeSavage added, "This isn't something that is just unique to pancreatic cancer. If we could take someone who has a chemo-resistant tumor and convert it into something that is sensitive to existing therapies again, we could give them a second chance."

Alex Trebek's Cancer Battle

Alex Trebek died of pancreatic cancer after a year and a half of battling pancreatic cancer, an aggressive form of cancer. While some celebrities choose to keep their cancer battles private, the “Jeopardy” star openly spoke about his treatment process with the public, and in doing so, educated millions on the disease. While hosting an episode of “Jeopardy!” in March 2019, Trebek shared with fans that he had been diagnosed with stage 4 pancreatic cancer , and would immediately start pursuing treatment. Despite the difficult journey, he remained the host of the TV trivia show and would keep viewers up to date on his progress periodically. At the time of his diagnosis, the one-year survival rate of pancreatic cancer was just 18%, but in June 2020 he made a special announcement that he’s “ beating the odds ” by surpassing the one-year-survival rate.   In addition to sharing good news, Trebek was also extremely open about the side-effects he experienced as a result of chemotherapy, and how it affected his mental state significantly at times. He later turned to an experimental therapy, developed by Dr. Patrick Soon-Shiong , which attempts to use multiple parts of the immune system to destroy tumors. RELATED: Alex Trebek’s Transparency About Pancreatic Cancer Battle Caused “Tremendous Spike” In Awareness & Helped Many Understand the Disease Trebek’s transparency made a huge impact in educating the public on pancreatic cancer, and made people more vigilant in spotting symptoms early. In fact, one “Jeopardy!” viewer said Trebek “ saved his life ” when the TV show host shared symptoms he experienced before his diagnosis, and the viewer realized he was also experiencing these symptoms. As a result, the viewer’s pancreatic cancer was caught at an early and treatable stage.

Patrick Swayze's Brave Battle

As for Patrick Swayze, his battle with the disease began when he was diagnosed with pancreatic cancer in March 2008. Before he passed, Swayze shared that he started experiencing symptoms of pancreatic cancer in December 2007 when he dealt with digestive issues. Again, pancreatic cancer often presents subtle symptoms early on, making it hard to notice.

In his memoir, he noted that he thought he was feeling bloated and that the feeling would eventually subside. “I had been having some digestive trouble,” he wrote . “It was mostly acid reflux and a kind of bloated feeling for a few weeks. I’ve had a sensitive stomach my whole life, so I hadn’t thought much of it, but lately, I just couldn’t shake the constant discomfort.” He was officially diagnosed a few months later. After an 18-month-long cancer battle, he died from the disease.

Learning about Pancreatic Cancer

Pancreatic cancer is an aggressive disease that is difficult to detect because symptoms, including jaundice and weight loss, typically present at a later stage in the cancer’s development. In a previous interview with SurvivorNet, Dr. Anirban Maitra , the co-leader of the Pancreatic Cancer Moon Shot at MD Anderson Cancer Center, explains what he typically sees when patients develop this disease. “Because the pancreas is inside the abdomen often doesn’t have symptoms that would tell you that something is wrong with your pancreas,” he says. “By the time individuals walk into the clinic with symptoms like jaundice, weight loss, back pain or diabetes, it’s often very late in the stage of the disease.” Detecting Pancreatic Cancer Early Is Crucial Parents, siblings and children of someone with pancreatic cancer are considered high risk for developing the disease because they are first-degree relatives of the individual. PGVs (pathogenic germline variants) are changes in reproductive cells (sperm or egg) that become part of the DNA in the cells of the offspring. Germline variants are passed from parents to their children, and are associated with increased risks of several cancer types, including pancreatic, ovarian and breast cancers. Germline mutations in ATM, BRCA1, BRCA2, CKDN2A, PALB2, PRSS1, STK11 and TP53 are associated with increased risk of pancreatic cancer. Jessica Everett , a genetic counselor at NYU Langone’s Perlmutter Cancer Center, encourages people in this category to look into possible screening options. “If you’re concerned about pancreatic cancer in your family, start by talking to a genetic counselor to learn more about your risk and what options you have,” Everett said. In addition, note that up to ten percent of pancreatic cancer cases are caused by inherited genetic syndromes. So, if two or more members of your family have had pancreatic cancer, or if you have pancreatic cysts, it’s worth asking your doctor to check for pancreatic cancer since you’re at high risk.

Progress in Pancreatic Cancer

Progress has been made over the last few years in the world of pancreatic cancer treatments. One clinical trial recently found that the drug Onivyde, in combination with chemotherapy in the so-called Nalirifox regimen, helped patients live longer compared with chemotherapy in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), according to Ipsen , the pharmaceutical company that bought the drug. "The prognosis for people diagnosed with pancreatic cancer is extremely poor and we plan to submit these new findings to the regulatory authority as, if approved, we believe this regimen could offer up an important new treatment option for people living with an aggressive and hard-to-treat cancer," Howard Mayer, Executive Vice President and Head of Research and Development for Ipsen, said . "We thank the patients who participated in the study, their families and their healthcare teams." The drug is currently approved in the U.S., Europe, and Asia in combination with fluorouracil and leucovorin as a treatment for mPDAC after disease progression and following gemcitabine-based therapy. Another example of progress being made comes in the form of immunotherapy, a type of cancer treatment that uses your own immune system to fight cancer. "Up until now, immunotherapy hasn't had a big role," Dr. Allyson Ocean , a medical oncologist at Weill Cornell Medical Center, previously told SurvivorNet. Dr. Allyson Ocean explains why pancreatic cancer is so hard to treat. A clinical trial led by researchers at the Perelman School of Medicine at the University of Pennsylvania, and sponsored by the Parker Institute for Cancer Immunotherapy, found "combination of chemotherapy with an immunotherapy meant to unleash the anticancer capacity of the immune system was effective against one of the hardest targets in cancer care, pancreatic cancer," said Penn Medicine . "The researchers found that in 34 patients with advanced pancreatic cancer randomized to receive the immunotherapy nivolumab with two chemotherapy drugs, nab-paclitaxel and gemcitabine, had a one-year survival rate of 57.7 percent, significantly greater than the historical average of 35 percent with chemotherapy alone," the institution said. Dr. Benjamin Musher , the director of medical oncology at the Dan L Duncan Comprehensive Cancer at Baylor St. Luke's Medical Center, recently said there were currently multiple " home-grown clinical trials testing novel immunotherapies in all stages of pancreatic cancer studies underway at Baylor St. Luke's. " But only about 5 percent of patients with pancreatic cancer participate in such studies. "We know that we are not going to improve outcomes without more patients enrolling," Musher said. In addition, there are immunotherapy clinical trial innovations being made to allow for multiple immunotherapeutic approaches to be tested and compared to one or several standard-of-care options within trials. In other words, "investigational treatments can be added or dropped from the trial over time, depending on preclinical and clinical evidence." "We're encouraged by the trend toward more innovative clinical trial designs to improve the drug development process and ultimately lead to better patient outcomes," PanCAN Chief Science Officer Lynn Matrisian said in a recent article from the Pancreatic Cancer Action Network . Clinical trials , in general, are research studies that compare the most effective known treatment for a specific type or stage of a disease with a new approach. Dr. Beth Karlan , a gynecologic oncologist with UCLA Health, previously told SurvivorNet that clinical trials can play an important role for some patients' treatment, but they also serve a larger purpose. "Clinical trials hopefully can benefit you, but it's also providing very, very vital information to the whole scientific community about the effectiveness of these treatments," Dr. Karlan said. "We need everyone to be partners with us if we're ever going to truly cure cancer or prevent people from having to die from cancer." That being said, there is no guarantee you'll receive more effective treatment than the standard of care, and clinical trials certainly aren't right for everyone. You should always talk with your doctor(s) before getting involved in one. Some risks to consider are:

• The risk of harm and/or side effects due to experimental treatments
• Researchers may be unaware of some potential side effects for experimental treatments
• The treatment may not work for you, even if it has worked for others

But if you've already decided that a clinical trial is right for you or you're just beginning to explore your treatment options, you should know that SurvivorNet has a tool for you . The SurvivorNet Clinical Trial Finder : an A.I. driven tool for patients to find clinical trial options for treatment. The tool is built on top of clinicaltrials.gov , a database maintained by the U.S. government that compiles privately and publicly funded clinical trials conducted around the world, and gives access to more than 100,000+ individual clinical trials, updated daily. "Clinical trials are critical to the development of new therapies, and as we live through this extraordinary revolution in genomics, immunotherapy and targeted therapy, it's clear that one of the most pressing needs for patients, clinical trials sponsors, and researchers is simply a better way to find patients," SurvivorNet CEO Steve Alperin said . "Even one percent more people successfully enrolled in clinical trials can change the world." Contributing: SurvivorNet Staff