Stepping up efforts to combat the rise of pancreatic cancer

A cancer with the lowest five-year survival rate of any major cancer is on the rise.

Pancreatic cancer rates have been steadily climbing, and it’s now the third-leading cause of cancer deaths in the country.

By 2020, it's expected to occupy the No. 2 spot. Rates are rising faster than any other cancer in the country.

What's driving this alarming climb?

“Advances for pancreatic cancer are lagging behind lung, colon and breast cancer, which have seen dramatic improvements from plummeting smoking rates, improved cancer detection methods and new therapies,” says Robert Wolff, M.D., professor of GI Medical Oncology and a program leader for MD Anderson’s Pancreatic Cancer Moon Shot™. “In contrast, pancreatic cancer is notoriously tricky to detect and treat.”

Unlike breast, prostate and colon cancers, which have effective screening methods, there are no reliable early-detection tests for pancreatic cancer. The pancreas is difficult to scan with current imaging technologies because of its location deep within the body. And pancreatic tumors are often surrounded by dense tissues that render drugs useless. Surgery is the only treatment known to cure the disease, but less than 20 percent of cases are operable.

“It's not that pancreatic cancer is becoming more lethal,” says Wolff. “It's as lethal as it ever has been, but we've done better with other cancers.” 

He say he's seeing more overweight, diabetic patients, who are twice as likely to develop pancreatic cancer.

“An average patient of mine has a body mass index between 30 and 35 — 30 is obese — has high blood pressure, diabetes or pre-diabetes, and takes a lipid-lowering drug,” Wolff says.

Making better lifestyle choices — eating healthier, exercising more and not smoking — would go a long way toward stemming the rising tide of pancreatic cancer, says Wolff, who estimates that 25 to 30 percent of pancreatic cancer cases are preventable.

On the research and treatment front, MD Anderson has pioneered many pancreatic cancer advancements, including neoadjuvant chemotherapy (chemotherapy given before surgery), the chemotherapy drug gemcitabine and the discovery of the genetic causes of pancreatic cancer.

Today, MD Anderson's pancreatic cancer experts are focusing their efforts on three main areas: novel therapeutic strategies, therapy prior to surgery and early detection. Here’s a closer look:

Gut check

In recent years, immune-blockade drugs have successfully treated some cancers by freeing the immune system to attack tumors. But pancreatic cancers have been stubbornly resistant. Could gut bacteria be to blame?

“There may be several reasons at work: the immune checkpoints targeted so far may not be relevant in pancreatic cancer, and the microenvironment (in the gut) that surrounds pancreatic cancer is strongly immunosuppressive, so T cells have a hard time getting activated around the tumor,” says Florencia McAllister, M.D., assistant professor of Clinical Cancer Prevention and director of MD Anderson’s clinic for high-risk pancreatic cancer patients.

She’s leading several animal studies targeting the gut microenvironment in combination with immunotherapy.

Preliminary results suggest that bacteria play an important role in directing immune responses and ultimately affecting pancreatic cancer.

Prehabilitation

Pancreatic cancer tumors release proteins that disturb the body's physiology and break down muscle, leaving patients frail and weak. Matthew Katz, M.D., co-leader of the Pancreatic Cancer Moon Shot and chief of the Pancreatic Surgery service at MD Anderson, is studying prehabilitation to strengthen pancreatic cancer patients for surgery and allow them to receive chemotherapy afterward.

Patients in the study either exercise moderately up to 30 minutes a day, five days a week and strength train two days a week, or receive a brochure about how to exercise safely. All patients receive fitness trackers to record their steps. Their fitness levels are tested up to seven months after surgery to see if their overall fitness and quality of life improve.

“Patients like it,” Katz says. “It's something they can really feel a part of, instead of just receiving chemotherapy or other drugs, this is actually something they can do themselves. And it makes them feel better.”

The researchers also are examining patients’ tumor specimens to see whether exercise expands the blood vessels supplying the tumors, making them more receptive to chemotherapy, as demonstrated in their mouse studies.

Quicker, focused radiation

Stereotactic body radiation therapy, or SBRT, allows radiologists to deliver high doses of focused radiation, with minimal side-effects, over five days instead of six weeks.

This allows out-of-town patients to spend just one week at MD Anderson getting this kind of care. The stress and financial implications for patients are minimized.

Katz is comparing SBRT and chemotherapy versus chemotherapy alone for patients with tumors that are located close to blood vessels, making them difficult to completely eradicate through surgery alone. The trial’s goal is to see which approach best enhances the effectiveness of surgery.

MD Anderson radiologists also are studying an intravenously administered radiation protector to shield the neighboring bowel from the toxic effects of high doses of radiation. In addition, they’re developing novel pathways to combine immunotherapy with radiation, and exploring radiomics, looking at patterns in imaging to pinpoint cancerous areas and help select patients for specific therapies.

Better detection

Because it's hard to detect, more than 85 percent of pancreatic cancer patients have advanced disease by the time they’re diagnosed. Less than 10 percent survive five years past diagnosis. 

“Our goal is to catch this disease at the earliest possible stage and come in with novel therapies to improve survival as much as possible,” says Anirban Maitra, M.B.B.S, scientific director of MD Anderson's Pancreatic Cancer Research Center and co-leader of the Pancreatic Cancer Moon Shot.

MD Anderson has launched a clinic for people at high risk of developing pancreatic cancer and is investigating several methods to screen for the disease, including liquid blood biopsies as a potential alternative to conventional, invasive needle biopsies. The technology analyzes a single vial of blood, and provides genetic information about the patient’s tumor, allowing doctors to “match” patients to the best clinical trial.

Information collected from this study will guide drug development and allow clinicians to track how a patient’s tumor responds to therapy.

Other advances

A new clinical trial at MD Anderson is currently enrolling patients to test a therapy that uses a patients’ own T cells to fight tumors. Several new drugs are entering Phase I clinical trials including IACS-10759, which targets abnormal metabolism within cancer cells. The drug is currently being used in an ongoing trial for acute myeloid leukemia. And researchers are developing therapies that inhibit abnormal genes and pathways in pancreatic cancer, including KRAS, which is mutated in as many as 95 percent of pancreatic cancer cases.

“I think there's no question that, compared to 10 or even five years ago, we've come a long way, and I do see long-term survivors all the time now — I mean, five years, seven years, even 10 years,” Maitra says. “We're making progress.”