Why Pancreatic Cancer, the Cause of Justice Ginsburg’s Death, is so Lethal

Supreme Court Justice Ruth Bader Ginsburg is not among us today.  

Sadly, we lost this iconic, trailblazing leader, who was the second woman to serve on the U.S. Supreme Court, and who was an inspiration and a role model to countless women across the globe, to metastatic pancreatic cancer. Among many stellar achievements, Ginsburg wrote opinions that eliminated gender-based stereotyping in legislation. She co-founded the first law journal on women’s rights, and helped to uphold the Affordable Care Act, which has given many Americans, including cancer patients, access to health care. It is stunning to realize that her tireless work took place throughout her decades-long struggle with multiple cancer diagnoses and treatments. 

Ruth Bader Ginsburg

As AACR Chief Executive Officer Margaret Foti, PhD, MD (hc), noted in her tweet, “[Justice Ginsburg] leaves a lasting legacy that benefits women in all professional fields including science and medicine.”  

In 1999, six years after Ginsburg’s appointment to the Supreme Court, she was treated for early-stage colon cancer. A decade later, she was treated for early-stage pancreatic cancer. In December 2018, she had two cancerous nodules removed from her lung. And in July 2020, she announced that she had been treated in February with chemotherapy for cancerous lesions on her liver. Ultimately, her pancreatic cancer returned and was the cause of her death. 

According to the National Cancer Institute, this year alone, more than 57,000 people will be diagnosed with pancreatic cancer and more than 47,000 people are expected to die in the United States, accounting for 7.8 percent of all cancer deaths in 2020. The five-year survival rate for pancreatic cancer overall is 10 percent, and for advanced disease, it is a dismal 2.9 percent. This poor prognosis is largely attributed to the difficulty in diagnosing this disease early, compounded by a dearth of new treatment options. 

Until the end of 2019, there were no molecularly targeted therapies for pancreatic cancer. Major risk factors for this disease, whose signs and symptoms include jaundice, pain, and weight loss, are smoking, obesity, a personal history of diabetes or pancreatitis, a family history of pancreatic cancer, and certain hereditary conditions. Pancreatic cancers are largely treated with surgery, chemotherapy, and radiotherapy. 

In December 2019, the U.S. Food and Drug Administration approved the use of olaparib (Lynparza) for the maintenance treatment of adult patients whose metastatic pancreatic cancer carries certain genetic defects, mutations in the genes BRCA1 and BRCA2. These mutations account for about 4 to 7 percent of all pancreatic cancers diagnosed in the United States. Additionally, some patients whose pancreatic cancers test positive for the biomarker microsatellite instability-high can be treated with the immune checkpoint inhibitor pembrolizumab (Keytruda).  

Several new treatment options are being studied to treat pancreatic cancer. Efforts are being made to find ways to circumvent the immunosuppressive environment of the pancreatic cancer tumors to make them amenable to immunotherapeutic approaches, and to target the RAS oncogenic signaling pathway.  

Basic research into the origins of pancreatic cancer recurrence, published in Cancer Discovery, a journal of the American Association for Cancer Research (AACR), has shown a unique genomic landscape in untreated pancreatic cancer, highlighting the value of post-treatment tumor sampling to manage the disease efficiently. A study published in the AACR’s Cancer Epidemiology, Biomarkers & Prevention showed that a risk prediction model that combined genetic and clinical factors with circulating biomarkers could help identify people at significantly higher than normal risk of pancreatic cancer. Early detection is key to better outcomes in patients with cancer. 

To further basic science research in pancreatic cancer, in March 2020, The Pancreatic Cancer Collective, the strategic partnership of Lustgarten Foundation and Stand Up To Cancer (AACR is the Scientific Partner), awarded additional funding of up to $16 million to four teams of top researchers as part of its “New Therapies Challenge Grants.” The first round of funding was announced in November 2018. This latest funding will support research on targeting SHP2 in pancreatic cancer, exploiting DNA repair gene mutations in pancreatic cancer, immunotherapy targeting of mutant KRAS, and studying molecularly targeted radionuclide therapy via the Integrin αvb6. 

Scientific advances such as these, and the opportunity for cancer researchers to exchange ideas and learn about the latest developments in the field, such as at the upcoming AACR Virtual Special Conference: Pancreatic Cancer, to be held September 29-30, will hopefully help the cancer research community make progress against this deadly disease that has taken so many loved ones from their families.