The Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins

05/03/2024

Congratulations to Laura Wood, Ashley Kiemen, Denis Wirtz, Ralph Hruban and the pancreatic cancer research team on their exciting new paper in Nature (https://rdcu.be/dGpnV) describing the genetics of precancerous lesions (PanINs) of the pancreas in three dimensions. Really elegant and impactful science using a combination of digital pathology, artificial intelligence and cutting-edge genetics.

03/08/2024

Please join us for the 2024 Sol Goldman Pancreatic Cancer Research Center's 10th annual International Think Tank! This year the topic is artificial intelligence and pancreatic cancer. The conference is virtual, and it is free! To learn more:

The 10th Annual Sol Goldman Pancreatic Cancer Research Center Think TankHosted by Ralph Hruban, M.D., and Laura Wood, M.D., Ph.D.April 3, 202408:30 AM - 12:00 PM EST

11/07/2023

Quitting smoking shown to decrease the risk of pancreatic cancer!

Cigarette smoking is one of the leading preventable causes of pancreatic cancer. In most studies, smoking ci******es doubles one’s risk of developing pancreatic cancer. Veronica Setiawan and colleagues from the University of Southern California just completed a study of cigarette smoking, and the good news is that they found that quitting smoking can reduce the risk of developing pancreatic cancer ! In an analysis of over 180,000 people reported in the journal Cancer Causes and Control (see https://link.springer.com/article/10.1007/s10552-023-01811-x and below), they found that people who smoked more than 50 pack-years (a pack year is calculated by multiplying the number of packs of ci******es smoked per day times the number of years a person has smoked) had an almost doubled risk of pancreatic cancer. Importantly, they found that every year a person quit smoking corresponded to a 9% decreased excess risk of developing pancreatic cancer! This was especially true for people who quit before the age of 65.
The message is simple- Don’t smoke, and if you do, quit smoking! It may save your life!

Reference: Bogumil D, Stram D, Preston DL, Pandol SJ, Wu AH, McKean-Cowdin R, Conti DV, Setiawan VW. Excess pancreatic cancer risk due to smoking and modifying effect of quitting smoking: The Multiethnic Cohort Study. Cancer Causes Control. 2023 Nov 4. doi: 10.1007/s10552-023-01811-x. Epub ahead of print. PMID: 37924460.

Purpose Risk factors for pancreatic cancer include racial/ethnic disparities and smoking. However, risk trajectories by smoking history and race/ethnicity are unknown. We examined the association of smoking with pancreatic cancer by race/ethnicity to generate age-specific incidence estimates by smok...

09/20/2023

Neoadjuvant therapy vs. straight to surgery
Patients with a surgically resectable pancreatic cancer often ask the question, “should I get chemotherapy before my surgery or should I go straight to surgery?” Chemotherapy before surgery is called “neoadjuvant” therapy, and for a number of years it seemed the best way to go. This conclusion was larger based on work from a research team at the MD Anderson Cancer Center (see references #1 and #2 below). Indeed, several studies reported that both life expectancy (LE) and quality-adjusted life expectancy (QALE) was better for patients who underwent neoadjuvant therapy than it was for patients who underwent surgery first, followed by chemotherapy after surgery (see reference #2 below).
A recent paper presented at the 2023 American Society of Clinical Oncology Meeting II (Short-course neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer: A multicenter randomized phase-II trial (NORPACT-1). | Journal of Clinical Oncology (ascopubs.org)) questions the impact of neoadjuvant therapy. In this paper, a team from Europe, reported the results of a randomized phase II trial conducted from 2017 to 2021.In the trial, called NORPACT-1, 140 patients were randomly assigned to either receive neoadjuvant FOLFIRINOX, or to undergo surgery first (upfront surgery). Surprisingly, the average overall survival was lower in the patients who received neoadjuvant therapy (25.1 months) than it was in the patients who underwent upfront surgery (38.5 months).
From these results, the authors concluded “Neoadjuvant FOLFIRINOX did not improve OS compared with upfront surgery in resectable pancreatic head cancer. Our results do not support neoadjuvant chemotherapy as standard of care for these patients.”
Where does this leave us? Unfortunately, as happens all too often in medicine, the data aren’t clear. Although many studies support the use of adjuvant therapy in patients with resectable pancreatic cancer, some studies, such as this one, do not. This means the decision of whether or not to go with neoadjuvant therapy or have upfront surgery, should very much be a personal decision based on thoughtful discussions between the patient and their health care provider. Some patients may “want their cancer out” and prefer upfront surgery. Others may wish to see how their cancer responds to chemotherapy before having surgery. Simply put, every patient should be fully informed, and should have a voice in their treatment.

References:
1. Raut CP, Evans DB, Crane CH, Pisters PW, Wolff RA. Neoadjuvant therapy for resectable pancreatic cancer. Surg Oncol Clin N Am. 2004 Oct;13(4):639-61
2. de Geus SW, Evans DB, Bliss LA, Eskander MF, Smith JK, Wolff RA, Miksad RA, Weinstein MC, Tseng JF. Neoadjuvant therapy versus upfront surgical strategies in resectable pancreatic cancer: A Markov decision analysis. Eur J Surg Oncol. 2016 Oct;42(10):1552-60. doi: 10.1016/j.ejso.2016.07.016.

05/22/2023

One Sunday May 22nd, members of PanCAN Washington D.C./Baltimore visited the pancreatic cancer team at Johns Hopkins to learn about our clinical, research and educational efforts. Visitors from PanCAN had the opportunity to meet with members of the Hopkins team in small groups. This allowed for patients and their families to learn about the latest advances, and, conversely, the Hopkins team had the opportunity to learn about the needs of those most impacted by the disease. A special thanks to Anna Somers from PanCAN, and Cordiela Lee from Hopkins, for all of their hard work organizing this wonderful event!

05/11/2023

Personalized vaccine to treat pancreatic cancer
A remarkable study was recently published by Rojas and colleagues in the journal Nature (Vaccine boosts T cells that target pancreatic tumours (nature.com)) . In their study, sixteen people underwent surgery for pancreatic cancer. The removed cancer was then analyzed, and a personal mRNA vaccine was developed to target 20 unique features (neoantigens) of each of the sixteen cancers. Each participant was then vaccinated with their personal vaccine, and received chemotherapy and an immune check point inhibitor. The results were remarkable. The authors showed that some patients developed an immune reaction (a T cell response) to the unique features present on their cancers. Although half of the patients did not respond, those that did had no evidence of disease 18 months after surgery.
The generation of personalized therapies can be extremely expensive, and this approach has a long way to go (Phase 2 and phase 3 trials are needed), this study “established the feasibility of using mRNA-based neoantigen vaccines for pancreatic cancer.”

04/20/2023

Ashley Kiemen, Ph.D., a new assistant professor in the Goldman Center, received the Lustgarten Foundation-AACR Carrer Development Award for Pancreatic Cancer Research in honor of Ruth Bader Ginsburg. This award honors the life and legacy of Justice Ginsburg, who worked tirelessly to advance gender equality, even while battling pancreatic cancer.

09/23/2021

Hopkins Team Helps Define Protein Expression Patterns in Pancreatic Cancer
A team of scientists from the Sol Goldman Pancreatic Cancer Research Center published a landmark paper in the journal Cell. The study, the result of an international collaborative effort, compared the proteins made by pancreatic cancer cells to the proteins made by normal cells in the pancreas. In so doing, the team defined the ways in which pancreatic cancer differs from normal. The team used the technology called “mass spectrometry” to characterize the proteins, glycoproteins (proteins with sugar molecules added onto the proteins), and phosphoproteins (proteins with phosphate molecules added). Many thousands of proteins were identified, and the results deposited in publically available databases for other researchers to use.
Why is this study important? The study is important for three reasons. First, many of the known cancer markers are glycoproteins. The discovery of glycoproteins made at high levels therefore identifies potential new pancreatic cancer markers. Second, some phosphoproteins are targetable therapeutically. The discovery of phosphoproteins made at high levels in pancreatic cancer cells therefore identifies a number of potential new targets for therapy. Third, the database is huge and will be shared freely. It is hoped that scientists will take advantage of it for years to come.
To learn more, visit: https://www.hopkinsmedicine.org/news/newsroom/news-releases/unique-aspects-of-pancreatic-cancer-proteins-could-lead-to-early-detection-new-treatments

Large scale 'proteogenomics' study suggests new targets for this deadly disease

05/06/2021

You are invited! Please spread the word. Fellows, students, trainees and faculty are all welcome!

The 2021 Sol Goldman Pancreatic Cancer Research Center International Think Tank
Hosted by Bert Vogelstein, M.D. and Ralph Hruban, M.D.
Targeting KRAS
Jun 16, 2021 08:30 AM – 11:30 AM Eastern Time
https://pathology.jhu.edu/pancreas/think-tank-kras

Please join us for an exciting and informative think tank on targeting KRAS! The think tank will be held by Zoom and will include some of the leading experts on targeting mutant KRAS.
Speakers include:

Mariano Barbacid, Ph.D., AXA-CNIO Professor of Molecular Oncology
Centro Nacional de Investigaciones Oncológicas (CNIO)
Spanish National Cancer Research Center
“In search of Therapeutic Strategies Against KRAS Driven Pancreatic Tumors”

Piro Lito, M.D., Ph.D., Assistant Member and Attending Physician
Human Oncology & Pathogenesis Program
Memorial Sloan Kettering Cancer Center
“Novel Insights into the Regulation of Mutant KRAS”

Yi Liu, Ph.D., CEO, Co-founder
Kumquat Bioscience
“Developing KRAS Inhibitors for Pancreatic Cancer Treatment”

Darryl B. McConnell, Ph.D., Senior Vice President
Research Site Head Austria
Bei Boehringer Ingelheim RCV GmbH & Co Kg
“The KRAS Drugs en Route”

Kevan M. Shokat, Ph.D., Professor, Department of Cellular & Molecular Chemistry
UCSF Helen Diller Family Comprehensive Cancer Center
“Chemical and Immunological Strategies for Directly Targeting KRAS”

Shibin Zhou, M.D., Ph.D., Associate Professor of Oncology
Sidney Kimmel Comprehensive Cancer Center
Director, Experimental Therapeutics, Ludwig Center for Cancer Genetics
“Redirecting T cells to Kill Cancer Cells with RAS Mutations”

To register in advance for this webinar:
https://jhjhm.zoom.us/webinar/register/WN_yodY855DSt69cc_OlXVqJQ

Or an H.323/SIP room system:
H.323:
162.255.37.11 (US West)
162.255.36.11 (US East)
69.174.57.160 (Canada Toronto)
65.39.152.160 (Canada Vancouver)
Meeting ID: 912 5259 4345
Passcode: 379075
SIP: 91252594345@zoomcrc.com
Passcode: 379075

10/27/2020

The Sol Goldman Center held its International Think Tank by Zoom this year! The focus was on the important topic of pancreatic cysts and precancers. This included "intraductal papillary mucinous neoplasms," and other precancerous lesions of the pancreas. Over 40 scientists participated, including prominent scientists from Japan, The Netherlands, Italy, Israel, and from all across the US.
Dr. Laura Wood gave the keynote, and even though the conference was held by Zoom, the day was filled with lively thought provoking discussions.

06/22/2020

2020 AACR Team Science Prize

The 2020 Team Science Prize from the American Association for Cancer Research was awarded to The Cancer Genome Atlas (TCGA). https://www.aacr.org/about-the-aacr/newsroom/news-releases/aacr-to-recognize-the-cancer-genome-atlas-tcga-founding-members-and-current-project-team-with-2020-team-science-awards/ The TCGA led an effort to sequence the DNA of all major cancer types. Ralph Hruban, M.D. from Johns Hopkins was included as one of the recipients of the AACR’s Team Science Prize as he co-led, together with Benjamin Raphael, the TCGA’s effort to sequence pancreatic cancer (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964983/). This is an amazing third time that the pancreatic cancer team at Hopkins has been recognized with the Team Science Award. The Hopkins team won it in 2013 for the first sequencing of all of the genes in pancreatic cancer, in 2017 for new approaches to the early detection of cancer (the “liquid biopsy”), and now again in 2020. These awards highlight the collaborative spirit that characterizes the pancreatic cancer research team at Johns Hopkins.

The AACR to recognize the founding members and the current project team associated with TCGA with 2020 AACR Team Science Awards.

02/18/2020

Enormous study of the DNA changes across 38 tumor types

The journal Nature just published (https://www.nature.com/collections/afdejfafdb and https://www.nature.com/articles/s41586-020-1969-6) a series of remarkable papers that integrate a number of large studies of the genetic (DNA) changes in a large number of cancer types. A number of faculty in the Sol Goldman Pancreatic Cancer Research Center participated in these studies. For example, the paper “Pan-cancer analysis of whole genomes,” integrated 2,658 whole-cancer genomes (studies of all of the DNA changes) across 38 cancer types, including pancreatic cancer. The investigators used data from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), and found that the average cancer has 4 to 5 “driver” mutations (mutations that clearly promote cancer growth), and that “catastrophic” genetic events, called chromothripsis, are more common and occur earlier than previously thought. The driver mutations for pancreatic cancer are usually in the KRAS, TP53, SMAD4 and p16/CDKN2A genes. Large scale studies such as these that integrate multiple datasets can be powerful as they can detect subtle patterns that can be missed in smaller studies.

02/04/2020

New living cell line of precancer of the pancreas created

Investigators from the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins recently published the first report of a cell line derived from an intraductal tubulopapillary neoplasm (ITPN) of the pancreas. This study, co-lead by principal investigators Dr. Laura Wood and Dr. Nicholas Roberts, was published in the journal Laboratory Investigation (https://www.ncbi.nlm.nih.gov/pubmed/32005909 ). It reports the molecular and functional characterization of this new cell line. To create the cell line, the authors used a combination of three-dimensional organoid culture and traditional two-dimensional cell culture. Intriguingly, they demonstrate that the cancer-associated properties of the cell line, such as colony formation and invasion, are intermediate between normal ductal cells and bona fide invasive pancreatic cancer cells, consistent with its identity as a precancerous lesion. This novel cell line represents an important model for further investigation of ITPNs and precancerous pancreatic lesions more generally. Moreover, it highlights three-dimensional culture as a technique to propagate early neoplasms in culture, with the potential to transition to traditional two-dimensional approaches for further studies.

01/24/2020

More early stage pancreatic cancers are being discovered!

A team led by Dr. Michael Goggins in the Sol Goldman Center just published an extensive review of pancreatic cancers reported in the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database (Blackford et al, J Natl Cancer Inst. 2020 Jan 20; https://www.ncbi.nlm.nih.gov/pubmed/31958122 ). They found that the incidence (number) of early stage (stage IA) pancreatic cancers is increasing. Coupled with this increase, they found that the average age of patients with stage I disease is decreasing. They also report that patients with Stage IA disease are more likely to carry insurance (versus Medicaid/none) than are higher-stage cases.

These findings are exciting as it suggests hope for the early detection of pancreatic cancer. Or, as the authors write: “these trends may be the result of improved early diagnosis and early detection.” They also suggest that access to healthcare (insurance) is critical.

J Natl Cancer Inst. 2020 Jan 20. pii: djaa004. doi: 10.1093/jnci/djaa004. [Epub ahead of print]

01/08/2020

The American Cancer Society just published, in the journal “CA: A Cancer Journal for Clinicians,” the latest cancer statistics in the United States (https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21590). The authors report that “In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted.”
The authors estimate that in 2020 approximately 57,600 Americans will be diagnosed with pancreatic cancer, and 47,050 will die from pancreatic cancer. In a hopeful sign, the five-year relative survival rate for patients with pancreatic cancer is 9%, better, but still way too low!
The report highlights the importance of smoking cessation, weight control and early detection in reducing cancer deaths. For patients with pancreatic cancer, the study highlights the importance of early detection. Patients with localized disease had a 37% five-year survival, patients with regional disease a five-year survival rate of 12% and patients with distant disease a five-year survival rate of only 3%.
We should all be encouraged by the many lives saved with the remarkable decline in overall cancer rates. The study does, however, painfully highlight the work that needs to be done fighting pancreatic cancer. New approaches to early detection, and new therapies are sorely needed.

01/06/2020

Two papers highlight the risk of recurrence after the surgical resection of an intraductal papillary mucinous neoplasm of the pancreas
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are non-invasive precancerous lesions, some of which, over time progress to invasive pancreatic cancer. If an intraductal papillary mucinous neoplasms of the pancreas is removed, it will not progress to invasive cancer. Intraductal papillary mucinous neoplasms of the pancreas therefore represent an opportunity to cure a pancreas tumor, before it becomes cancer.
While removing an intraductal papillary mucinous neoplasm of the pancreas prevents the lesion that was removed from progressing to pancreas, the remnant (remaining) pancreas remains at risk. Just as patients who have had a colon polyp removed need to be more carefully monitored for more colon tumors, so too do patients who have had an intraductal papillary mucinous neoplasms of the pancreas surgically resected need to be monitored for additional pancreas tumors.
Two papers that were just published help answer important questions in the post-operative monitoring of these patients.
https://www.ncbi.nlm.nih.gov/pubmed/30413822
https://www.ncbi.nlm.nih.gov/pubmed/31463655
First, what is the magnitude of the risk of recurrence after the surgical resection of an intraductal papillary mucinous neoplasm of the pancreas? The reported risk varies, but these two papers, combined with several previously published papers, suggest that the risk of getting a new significant lesion in the remnant pancreas in the five years after surgery is in the range of 5-15%. Patients who had an intraductal papillary mucinous neoplasm of the pancreas with “high-grade dysplasia” resected have a higher risk than do patients who had an intraductal papillary mucinous neoplasm of the pancreas with “low-grade dysplasia” resected.
Second, does the risk ever go down to zero, or do we have to monitor patients indefinitely? Both studies suggest that the risk persists. One cannot identify a certain number of years after surgery where it is safe to stop monitoring. In fact, both studies show that the risk persists well beyond five years after surgery.
Why is this important? These studies reinforce a growing body of literature that emphasize the importance of monitoring patients who have had an intraductal papillary mucinous neoplasm of the pancreas resected. They also show that this monitoring should, when clinically indicated, be indefinite.

For more information, visit: http://pathology.jhu.edu/pancreas/cyst/index.php

Am J Gastroenterol. 2019 Mar;114(3):524-529. doi: 10.1038/s41395-018-0403-2.

12/21/2019

Warm your heart

Warm your heart with an end of the year gift in support of the pancreatic cancer research team at Johns Hopkins! Giving is simple (just visit http://pathology.jhu.edu/pancreas/support.php) and impactful. Private giving supports our creative young scientists, private giving helps us pursue new and exciting leads, and most of all, private giving helps us fight pancreatic cancer!
Happy holidays to all, and THANK YOU for your support!

While all efforts to advance our understanding of pancreas cancer are proceeding at a record pace, we have more leads than we have resources to pursue them. Financial support is needed to continue these efforts.