Pancreatic Cancer
Pancreatic cancer is a malignant neoplasm originating from transformed cells in the pancreas, an organ essential for digestion and glucose regulation. The majority of pancreatic cancers arise from the exocrine component, particularly the ductal epithelium, but neoplasms can also originate from the endocrine islets. The pathogenesis involves a multistep process of genetic and epigenetic alterations, including mutations in oncogenes such as KRAS, tumor suppressor genes like TP53, and dysregulation of cellular signaling pathways. Chronic inflammation, as seen in chronic pancreatitis, and certain hereditary syndromes, such as those involving BRCA mutations, contribute to increased risk. Pancreatic cancer is characterized by aggressive local invasion, early metastasis, and a dense desmoplastic stroma that impedes drug delivery and immune cell infiltration. The disease exerts significant health impacts due to its late presentation, rapid progression, and limited therapeutic options, resulting in high morbidity and mortality. Patients often experience profound weight loss, abdominal pain, obstructive jaundice, and metabolic derangements, with a substantial reduction in quality of life and overall survival.
Pancreatic ductal adenocarcinoma is the most prevalent form of pancreatic cancer, accounting for over 90% of cases. It arises from the epithelial lining of the pancreatic ducts and is characterized by an aggressive clinical course, marked desmoplastic reaction, and resistance to conventional therapies. PDAC typically presents at an advanced stage due to its asymptomatic early development and rapid progression, often involving local invasion and distant metastases at diagnosis.
Pancreatic neuroendocrine tumors originate from the hormone-producing islet cells of the pancreas. They represent a minority of pancreatic malignancies but display a wide spectrum of biological behavior, ranging from indolent, well-differentiated tumors to highly aggressive, poorly differentiated carcinomas. PNETs may be functional, secreting hormones that cause specific clinical syndromes, or non-functional, presenting with mass effect or metastatic disease.
Acinar cell carcinoma is a rare exocrine tumor derived from the acinar cells responsible for enzyme production. These tumors often exhibit distinct histopathological features, including acinar differentiation and the production of pancreatic enzymes, which can occasionally lead to paraneoplastic syndromes such as lipase hypersecretion. Acinar cell carcinomas tend to have a better prognosis than PDAC but are frequently diagnosed at an advanced stage.
Pancreatoblastoma is a rare malignant epithelial neoplasm most commonly observed in children. It is characterized by a combination of acinar, ductal, and sometimes neuroendocrine differentiation. Pancreatoblastomas often present as large abdominal masses and may be associated with elevated serum alpha-fetoprotein. Despite their aggressive nature, these tumors can be responsive to multimodal therapy.
Mucinous cystic neoplasms are cystic lesions of the pancreas that possess malignant potential. When invasive carcinoma arises within an MCN, it is termed mucinous cystic neoplasm with invasive carcinoma. These tumors predominantly affect middle-aged women and are typically located in the body or tail of the pancreas. The prognosis is generally more favorable than that of PDAC when detected early.
Pancreatic cancer is the seventh leading cause of cancer-related mortality worldwide, with an estimated 495,000 new cases and 466,000 deaths annually according to GLOBOCAN 2020 data. The incidence varies geographically, being higher in developed countries such as the United States and Western Europe. In the United States, it is the third leading cause of cancer death, with a lifetime risk of approximately 1 in 64. The age-adjusted incidence rate is about 13 per 100,000 individuals, and the disease predominantly affects older adults, with a median age at diagnosis of 70 years. There is a slight male predominance, and risk factors include smoking, obesity, diabetes mellitus, chronic pancreatitis, and certain hereditary cancer syndromes. The five-year overall survival rate remains dismal, at approximately 10%, largely due to late-stage diagnosis and limited efficacy of current treatments.
The diagnosis of pancreatic cancer relies on a combination of clinical assessment, laboratory testing, imaging modalities, and histopathological confirmation. Initial evaluation includes a thorough history and physical examination, focusing on symptoms such as jaundice, weight loss, abdominal pain, and new-onset diabetes. Laboratory studies may reveal elevated liver enzymes, hyperbilirubinemia, and tumor markers such as carbohydrate antigen 19-9 (CA 19-9), though these are not specific. Cross-sectional imaging, particularly contrast-enhanced computed tomography (CT) of the abdomen, is the cornerstone for detecting pancreatic masses, assessing local invasion, and evaluating for metastatic disease. Magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) offer additional sensitivity for small lesions and can guide fine-needle aspiration (FNA) for cytological diagnosis. Endoscopic retrograde cholangiopancreatography (ERCP) is useful for biliary decompression and obtaining ductal brushings when indicated. Definitive diagnosis requires histological confirmation from biopsy specimens, which also facilitate molecular profiling for therapeutic stratification. Staging is performed in accordance with the American Joint Committee on Cancer (AJCC) TNM system, integrating tumor size, nodal involvement, and presence of distant metastases.
Irinotecan hydrochloride liposome injection and irinotecan liposome injection are formulations of the topoisomerase I inhibitor irinotecan encapsulated in liposomes, designed to enhance drug delivery and prolong systemic exposure, and are used in the treatment of pancreatic cancer, particularly in patients who have progressed on prior therapies. Belzutifan is an oral inhibitor of hypoxia-inducible factor-2 alpha (HIF-2α) and is employed in the management of pancreatic cancer, targeting tumor adaptation to hypoxic microenvironments. Sulfatinib, also known as surufatinib, is an oral small-molecule inhibitor of multiple receptor tyrosine kinases, including VEGFR, FGFR, and CSF-1R, and is indicated for the treatment of pancreatic neuroendocrine tumors by impeding angiogenesis and modulating tumor-associated immune cells. Irinotecan sucrosofate, administered as a nanoliposomal irinotecan injection, is a specialized formulation designed for improved pharmacokinetics, offering an additional therapeutic option for patients with advanced pancreatic cancer. Olaparib is an oral poly (ADP-ribose) polymerase (PARP) inhibitor indicated for patients with germline BRCA-mutated metastatic pancreatic cancer, exploiting synthetic lethality in tumor cells with defective DNA repair mechanisms. Cabozantinib S-malate is a tyrosine kinase inhibitor targeting MET, VEGFR, and other kinases, and is used in the treatment of pancreatic cancer to inhibit tumor growth, angiogenesis, and metastatic progression. Sunitinib malate is another multi-targeted tyrosine kinase inhibitor, approved for the management of advanced pancreatic neuroendocrine tumors, where it exerts anti-proliferative and anti-angiogenic effects. Nab-paclitaxel, a nanoparticle albumin-bound formulation of paclitaxel, is administered in combination regimens for pancreatic cancer, enhancing drug delivery to tumor tissue and improving response rates. Erlotinib hydrochloride is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in combination with gemcitabine for the treatment of locally advanced, unresectable, or metastatic pancreatic cancer, targeting aberrant EGFR signaling pathways. Everolimus is an oral inhibitor of the mammalian target of rapamycin (mTOR) pathway, indicated for the treatment of advanced pancreatic neuroendocrine tumors, where it suppresses cellular proliferation and angiogenesis.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
| irinotecan hydrochloride liposome injection; irinotecan liposome injection | ||||
 | belzutifan (Rec INN; USAN) | 1672668-24-4 | C17 H12 F3 N O4 S | 383.342 |
 | sulfatinib; surufatinib (Rec INN; USAN) | 1308672-74-3 | C24 H28 N6 O3 S | 480.583 |
| Irinotecan sucrosofate; liposome irinotecan injection; nanoliposomal irinotecan sucrosofate | ||||
 | olaparib (Rec INN; USAN) | 763113-22-0 | C24 H23 F N4 O3 | 434.463 |
 | cabozantinib S-malate (Prop INNM; USAN) | 1140909-48-3; 849217-68-1 (free base) | C28 H24 F N3 O5 . C4 H6 O5 | 635.593 |
 | sunitinib malate (Rec INNM; USAN) | 341031-54-7; 557795-19-4 (free base) | C22 H27 F N4 O2 . C4 H6 O5 | 532.561 |
| nab-paclitaxel; paclitaxel nanoparticles | ||||
 | erlotinib hydrochloride (Rec INNM; USAN) | 183319-69-9; 183321-74-6 (free base) | C22 H23 N3 O4 . Cl H | 429.897 |
 | everolimus (Rec INN; USAN) | 159351-69-6 | C53 H83 N O14 | 958.224 |
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