Pancreatic cancer begins in the pancreas, an organ located in the abdomen that helps in digestion and regulates blood sugar. The pancreas produces enzymes that aid digestion and hormones like insulin and glucagon that regulate blood sugar levels. There are two main types of pancreatic cancer – exocrine tumors and endocrine tumors. Exocrine tumors account for about 95% of pancreatic cancers and develop in the pancreatic cells that produce enzymes to help break down and absorb nutrients in food. Endocrine tumors develop in the hormone-producing cells and account for the remaining 5% of cases.
Risk Factors and Symptoms
Some of the main risk factors for developing Pancreatic Cancer include age (over 60 years), smoking, obesity, family history of pancreatic cancer, long-standing pancreatitis, diabetes and race among others. Symptoms are often vague in the initial stages but may include abdominal or back pain, jaundice, weight loss, nausea and loss of appetite. Due to non-specific symptoms, pancreatic cancer is usually detected at an advanced stage when it has already spread to other organs. This makes surgical resection difficult and treatment options limited. More specific biomarkers are needed to help detect the disease at an earlier stage when surgery may still be possible to significantly improve outcomes.
Diagnostic Advances
A combination of blood tests, imaging and biopsy are typically used to diagnose pancreatic cancer. Several changes have been made over the years to enhance early detection. Improved cross-sectional imaging using endoscopic ultrasound (EUS), computed tomography (CT) and magnetic resonance imaging (MRI) allow for more precise visualization of the pancreas. EUS plays an important role by providing high-resolution images close to the actual organ. EUS-guided fine needle aspiration biopsy is widely used to diagnose and stage pancreatic tumors. Molecular pathology is leveraging advances in genomics and proteomics to identify biomarkers from tissue and blood samples to potentially detect pancreatic cancer earlier. Liquid biopsies that detect circulating tumor DNA in blood are emerging and need further research to determine their utility as a screening or risk assessment tool.
Surgical Options for Pancreatic Cancer Treatment
Surgery offers the only potential cure for pancreatic cancer but is only possible in about 15-20% of cases when the cancer is still localized within the pancreas. The two main surgeries are the Whipple procedure, also known as pancreaticoduodenectomy, for tumors in the head of the pancreas and distal pancreatectomy for cancers in the body or tail. The Whipple procedure removes the head of the pancreas along with the first part of the small intestine, part of the stomach, the bile duct and gallbladder. A distal pancreatectomy involves removal of the tail and body of the pancreas along with the spleen. Both operations are complex and have risks of serious complications given the organ’s location deep in the abdomen. Advances in minimally invasive surgery using robotics and laparoscopy are gradually helping improve surgical outcomes.
Chemotherapy and Radiation Options
For most pancreatic cancer patients whose tumor has spread beyond the pancreas, chemotherapy is the main treatment option. Gemcitabine (Gemzar) used to be the standard chemotherapy drug for pancreatic cancer. More recent combination regimens that pair Gemcitabine with newer drugs like Abraxane, Onivyde or FOLFIRINOX have improved outcomes by a few months on average. Targeted therapies that inhibit specific genes driving cancer growth are also beginning to show promise for select patients when used along with chemotherapy. External beam radiation therapy often combined with chemotherapy is another option to control symptoms or prolong survival in advanced disease. Brachytherapy, also known as internal radiation using implanted radioactive seeds in conjunction with chemotherapy may help improve local control. Researchers continue exploring novel systemic agents as well as radiation techniques like proton beam therapy to better target tumors while sparing healthy tissues from radiation damage.
Immunotherapy Approaches
By harnessing the body’s own immune system, immunotherapy has transformed outcomes for multiple cancers like melanoma and lung cancer over the last decade. Several immunotherapy drugs approved for other solid tumors are under active investigation for pancreatic cancer. Checkpoint inhibitors that target PD-1, PD-L1 and CTLA4 are among the most studied. So far, only the PD-1 inhibitor pembrolizumab (Keytruda) has gained FDA approval along with chemotherapy for advanced pancreatic cancer. Ongoing clinical trials are evaluating immunotherapy drugs alone or in combination with chemotherapy, targeted therapies, radiation therapy and oncolytic viruses to potentially improve survival. Challenges include the dense fibrotic tissue surrounding pancreatic tumors which limits immune cell infiltration. Newer pre-clinical research focuses on depleting this dense stroma barrier and strategies like personalized cancer vaccines to achieve better immunotherapy responses.
Despite recent progress, pancreatic cancer remains a major clinical challenge with a low overall 5-year survival of just 11%. Continued research efforts across disciplines involving better imaging, molecular diagnostics, innovative surgery, novel systemic agents and immunotherapy are critical to advance therapeutics for this disease. While biomarker-driven early detection and improved local therapies hold promise, most progress will likely emerge through well-designed clinical trials establishing effective multidisciplinary regimens for both localized and advanced disease. Unraveling the complex biology of pancreatic cancer at the genomic, proteomic and immune levels will drive the development of additional targeted and personalized treatment approaches with the goal of enhancing survival and quality of life for patients.