Today, November 17, is World Pancreatic Cancer Day.

Today, November 17, is World Pancreatic Cancer Day.

According to the American Cancer Society, Pancreatic Cancer (PancCa) accounts for about 3 % of all cancers in the US and about 7 % of cancer deaths.

In 2016, an estimated 53,070 people (27,670 men and 25,400 women) have been diagnosed with and about 41,780 people (21,450 men and 20,330 women) are dying of PancCa. The increase in incidence and death will turn PancCa into the second deadliest cancer by 2030 with a 5-year survival rate of less than 5 % for advanced and 15-20 % for local disease after tumor resection.

In the past 42 years several famous artists and scientists died of this really tough to treat, tough to have, tough to watch, …, tough to everything cancer. Ten who died between 1974 and today are listed below. The two that I remember most were Steve Jobs and Patrick Swayze. Their suffering went through the news. How painful must it have been for them to go through treatment trying to fight this merciless illness.

List of 10 famous patients who died of pancreatic cancer

2012: Sally Ride, physicist and astronaut

2011: Anne Francis, actress

2011: Steve Jobs, Apple CEO

2009: Patrick Swayze, Actor, dancer, singer, songwriter

2007: Luciano Pavarotti, operatic tenor

1996: Marcello Mastroianni, actor

1994: Bill Hicks, Comedian

1986: Donna Reed, actress

1977: Joan Crawford, actress

1974: Jack Benny, Comedian

When I worked in a research lab at Mt. Sinai in New York City, I remember our chair Dr. Sam Waxman say at a journal club when we discussed anti-angiogenic treatment for PancCa that this approach made sense because it is such a bloody cancer and very difficult to operate on. That was in the early 2000s and there is still no anti-angiogenic agent approved for pancreatic cancer.

Later, I worked on a targeted therapy project (IGF-1R) for PancCa and it was cancelled because it did not work – the phase III study did not meet the expectations. Why is it that there has been so little advancement over the past decades – just surgery (if it is not too advanced), radiation and chemotherapy. Few innovations have been achieved with two chemotherapeutics, one albumin-bound the other liposomal to reduce side effects to a certain extent.

Why is it that in the century of targeted therapy, immunotherapy, cancer vaccines etc. there is so little progress in the field of PancCa despite the obvious need?

In 2015, Garrido-Laguna and Hidalgo wrote a Nature Review about exactly this subject. It should help us understand a bit better.

The authors explain that prognosis is poor for most patients due to the fact that early stage pancreatic cancer is asymptomatic so that most patients are diagnosed with advanced stage disease when the tumor has spread already and cannot be entirely removed anymore. This is devastating because up to now surgery offers the best prospect of somewhat longer-term survival. An effective screening approach for early detection is not yet available either. On the other hand, preclinical transgenic mouse models suggest that PancCa is a systemic disease. Thus, a combination of surgery and systemic therapy should be the right treatment strategy.

Significant improvements in surgical techniques over the past decade have resulted in less perioperative morbidity and mortality for patients with resectable disease. Adding adjuvant chemotherapy has shown to be beneficial for these patients but did not lead to a cure. Most likely due to the fact that the tumor spread in form of micrometastases and surgical margins contained small but sufficient numbers of cancer cells. One hypothesis is to treat borderline resectable patients with neo-adjuvant chemotherapy before applying surgery. This concept is still controversely discussed and would require a multi-center, randomized study.

What about unrecectable disease when tumors have progressed beyond the possibility to be removed by surgery? In these patients chemotherapy can be combined with radiation depending on a biomarker called SMAD4 (tested in tumor tissue or blood samples) that may help identify patients that should be treated with chemo only. This approach yet has to be confirmed prospectively.

Some advances were made in metastatic disease according to Garrido-Laguna and Hidalgo using chemo combinations and testing novel targeted therapy approaches (also in combinations) like inhibitors of HER2, the RAS-pathway, Janus kinase, the PI3K-mTor pathway, PARP and immune system checkpoint proteins in addition to vaccines. Great effort is currently underway to identify biomarkers that may help select the right therapy for the right patients. The difficulty is that targeted approaches show some effect in some patients but not in others. I am using this very vague language on purpose to demonstrate how much still needs to be done to understand this very complex disease.

It’s certainly not that scientists don’t work hard for patients in high need – in contrary. It is rather that like so often, pancreatic cancer is just not a straight forward disease …..



About the Author:

Sanne has a mixed science/business background with a PhD in Mol. Oncology and an MBA in healthcare. She worked 12 years as a scientist in cancer research labs before she moved on towards life science/healthcare consulting and medical affairs. Sanne is inspired to function as a bridge to overcome gaps within the healthcare community through communication, medical education and support of clinical research ideas.

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