Pancreatic Cancer disease mechanism in adults
Pancreatic cancer is a particularly aggressive form of cancer originating in the tissues of the pancreas, an organ located deep within the abdomen that plays vital roles in digestion and blood sugar regulation. Understanding the disease mechanism in adults involves exploring the cellular and molecular changes that drive its development, progression, and resistance to treatment.
The vast majority of pancreatic cancers are adenocarcinomas that develop from the exocrine cells of the pancreas, specifically the ductal cells. The process begins with genetic mutations that accumulate over time, often influenced by risk factors such as smoking, chronic pancreatitis, obesity, and genetic predispositions. These mutations disrupt normal cellular processes, leading to uncontrolled cell growth and division.
One of the key molecular pathways involved in pancreatic cancer development is the mutation of the KRAS gene, which occurs in over 90% of cases. KRAS encodes a protein that transmits signals for cell growth and survival. When mutated, it becomes constitutively active, meaning it continuously signals cells to divide and evade apoptosis (programmed cell death), fostering tumor formation. Alongside KRAS mutations, additional genetic alterations often involve tumor suppressor genes such as TP53, CDKN2A, and SMAD4. Loss or inactivation of these genes further promotes malignant transformation by impairing the cell’s ability to regulate division, repair DNA damage, or undergo apoptosis.
The progression from normal ductal cells to invasive carcinoma involves a series of preneoplastic lesions called PanINs (pancreatic intraepithelial neoplasias). These lesions accumulate genetic mutations and cellular abnormalities, gradually evolving into invasive tumors that invade surrounding tissues and metastasize to distant organs like the liver, lungs, and peritoneal cavity.
At the cellular level, pancreatic tumors are characterized by a dense stromal reaction, or desmoplasia, composed of fibroblasts, immune cells, and extracellular matrix components. This stromal environment not only provides structural support but also contributes to tumor growth, immune evasion, and resistance to chemotherapy. The complex interaction between cancer cells and their microenvironment is a major obstacle in effective treatment.
On a molecular level, pancreatic cancer cells often exhibit alterations in signaling pathways such as PI3K/AKT, TGF-β, and Wnt/β-catenin, which support proliferation, invasion, and metastasis. These molecular changes enable the tumor to adapt to various stresses, including hypoxia and immune responses, facilitating disease progression.
In summary, pancreatic cancer in adults arises from a multifactorial genetic and molecular cascade that transforms normal ductal cells into invasive, metastatic tumors. Its development involves critical mutations in oncogenes and tumor suppressor genes, coupled with complex interactions within the tumor microenvironment. Unraveling these mechanisms is essential for developing targeted therapies and improving prognosis for this formidable disease.
