Outgoing AACR President: Big challenges remain in prevention, diagnosis, and treatment of pancreatic cancer

David A. Tuveson, MD, PhD, FAACR
David A. Tuveson, MD, PhD, FAACR

When U.S. President Joe Biden reignited his Cancer Moonshot initiative earlier this year with the ambitious goals of reducing the age-adjusted mortality of cancer by 50 percent over the next 25 years and improving the experience of living with and surviving cancer, it brought increased awareness to the cancer research community.

In his Presidential Address on Sunday, April 10, AACR President David A. Tuveson, MD, PhD, FAACR, elevated awareness of the unique challenges in the fight against pancreatic cancer and what it will take to achieve the targets of the Cancer Moonshot in this patient population.

Tuveson’s address, A Road Map to Defeat Pancreatic Cancer, can be viewed on the virtual platform by registered meeting participants through July 13, 2022.

Tuveson began by reminiscing about receiving a grant to study pancreatic cancer at the AACR Annual Meeting two decades ago.

“Twenty years ago, there weren’t a lot of pancreas cancer experts—I’m talking about oncologists, mostly—but there are today,” he recalled.

Even so, the current reality for pancreatic cancer patients includes some stark statistics. 

Many patients never see an expert in pancreas cancer, despite the growing ranks of specialists, and are treated instead by a generalist or internist, Tuveson noted. Moreover, a third of people with pancreas cancer never receive medicine for their illness, and only 11 percent survive five years.

“That’s actually an improvement from when I was in my early days, doubling what it was in 2000. So, we have improved, but we’re still far away,” Tuveson said. “So, how are we going to meet the presidential challenge?”

The answer lies in what he refers to as the “Seven Deadly Hallmarks of Pancreatic Cancer,” five of which are scientific and two are clinical:

  1. Chronic inflammation stimulates pancreatic cancer
  2. Desmoplastic stroma is a critical process in the disease
  3. Dysregulated metabolism promotes this cancer
  4. Cellular plasticity states may represent dependencies in pancreatic cancer
  5. For this cancer, oncogenic KRAS program is the predominant dependency
  6. Patients experience rapid deconditioning
  7. Early detection of pancreatic cancer does not exist

“We should treat early disease, and then we could actually learn more about the drugs we have and maybe try to prevent metastasis,” Tuveson said.

There’s also a need to develop methods to assess pancreatic tissue health.

“We know how to assess your heart health and your lung health, but how do you assess someone’s pancreatic health?” Tuveson asked. “Lots of people who present with type 3c diabetes—meaning diabetes when you’re older and you’re starting to lose weight—this is a crowd that is predisposed to getting pancreas cancer. Basically, their pancreas tissue is lost.” 

A singular approach will not be sufficient to defeat pancreatic cancer, Tuveson noted. The path forward needs to include establishing prevention tactics, developing diagnostics for early disease, and improving treatments.

“Our patients need this disease to go away, and it hasn’t happened. But it’s getting much better,” he said. “I’m actually very optimistic.”

Tuveson’s lab is among the collaborators in a randomized clinical trial at seven sites in the U.S. and Canada comparing two standard-of-care chemotherapy regimens in patients with stage 4 pancreatic cancer: modified folfirinox and gemcitabine/nab-paclitaxel. The Pancreatic Adenocarcinoma Signature Stratification for Treatment-01 trial, or PASS-01, seeks to determine whether the gene signatures from patient-derived organoids can be used to predict the outcomes of the patient.

“The real question we have is will this be the way to pick the better medicine for a patient, because the better medicines are coming online,” Tuveson said.