Pancreatic cancer is one of the most lethal cancers with a poor prognosis. However, recent advances in therapeutics and diagnostics are providing hope for better outcomes. This article discusses the current state of pancreatic cancer treatment and diagnosis.
Overview of Pancreatic Cancer
Pancreatic cancer occurs when abnormal and uncontrolled cell growth forms a malignant tumor in the pancreas. The pancreas is an organ located deep in the abdomen that plays an important role in digestion and regulating blood sugar levels. There are two main types of pancreatic cancer - exocrine pancreatic cancer which forms in the ducts or acinar cells, and endocrine pancreatic cancer which forms in the islet cells. Exocrine pancreatic cancer, also known as pancreatic ductal adenocarcinoma (PDAC), accounts for over 90% of pancreatic cancer cases.
Risk factors for developing pancreatic cancer include age over 60, smoking, obesity, diabetes, family history, chronic pancreatitis and certain genetic mutations. Surgery offers the only chance of cure but only about 20% of patients are candidates for surgery as the cancer is usually advanced at the time of diagnosis. The 5-year survival rate for pancreatic cancer is only around 9% making it one of the deadliest cancers. Improving early detection through better diagnostics and developing new therapies are urgently needed to combat this disease.
Advances in Diagnosis
Making an early and accurate diagnosis of pancreatic cancer remains challenging due to nonspecific symptoms and lack of reliable screening tests. However, new diagnostic techniques are improving detection capabilities. Endoscopic ultrasound (EUS) along with guided fine needle aspiration biopsy is now the most accurate non-surgical method to diagnose pancreatic cancer. EUS allows visualization of the pancreas and detection of small tumors as well as collection of tissue samples for analysis.
Blood-based biomarker tests are also enhancing diagnostic ability. The tumor marker CA19-9 is commonly measured but has limited utility as elevations can occur due to other pancreatic conditions. Newer biomarkers like DNA circulating tumor DNA (ctDNA) show promise in detecting molecular alterations from tumors that may serve as very specific indicators of pancreatic cancer. Combining multiple biomarkers into "signature profiles" through advanced analysis of blood samples now allows detection of early stage tumors with high accuracy.
Noninvasive imaging techniques continue advancing as well. Multidetector computed tomography (CT) scanning remains the primary imaging method but often misses small cancers. Magnetic resonance imaging (MRI) with contrast agents provides better soft tissue contrast resolution and detection of small tumors. Positron emission tomography (PET) scans now routinely incorporate CT imaging, known as PET/CT, to precisely localize abnormalities identified on PET. These combined anatomic and functional scans help identify both the primary tumor as well as metastasis with high sensitivity and specificity.
Advances in Treatment
Despite making headlines for approval of new drugs, pancreatic cancer continues to face major treatment challenges. Surgery, when feasible, offers the best chance of cure by complete surgical resection but recurrence is common. For most patients, surgery is not a viable option due to advanced stage at diagnosis. These patients undergo combination chemotherapy, often with the drugs gemcitabine or 5-fluorouracil, to try and control tumor growth.
Targeted therapy drugs that specifically interfere with pancreatic cancer therapeutics and diagnostics cell signaling pathways are beginning to show promise. Drugs that block epidermal growth factor receptor (EGFR), such as erlotinib, have modest benefits when combined with chemotherapy. Inhibition of vascular endothelial growth factor (VEGF) pathways through drugs like bevacizumab may enhance the effects of chemotherapy by limiting tumor blood supply.
Immunotherapy is an exciting new treatment frontier. Checkpoint inhibitors targeting proteins like PD-1/PD-L1 that help tumors evade immune detection have led to long-term remissions in some pancreatic cancer patients. Combining these immunotherapies with therapies that increase tumor immunogenicity, such as chemotherapy or targeted therapy drugs, show enhanced responses. T-cell therapies that specifically target tumor antigens present the potential for a "living drug" cure.
New chemotherapy combinations are also being explored. FOLFIRINOX, a combination of four chemo drugs, provides longer survival when compared to gemcitabine alone for selected patients. Nanoparticle drug delivery directly into tumors offers dose intensification possibilities. Research into pancreatic cancer biology and genomics will lead to individualized precision medicine approaches based on a patient's unique tumor mutations.
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