- Adenocarcinoma is a malignant tumor arising from glandular epithelial cells, which are responsible for producing and secreting substances such as mucus and digestive enzymes.
- These cancers exhibit significant heterogeneity in their molecular characteristics, clinical behavior, and treatment responses. Advances in genomic and molecular profiling have enabled a better understanding of their pathogenesis, leading to improved diagnostic and therapeutic strategies.
- Given the widespread presence of glandular tissue throughout the body, adenocarcinomas can develop in multiple organs. Most common types of adenocarcinoma are described below.
- Lung adenocarcinoma is the most common histological subtype of non-small cell lung cancer (NSCLC), accounting for approximately 40% of all lung cancer cases. It primarily arises in the alveolar epithelial cells and is frequently driven by genetic alterations in EGFR, KRAS, ALK, and ROS1. While smoking remains a primary risk factor, a significant proportion of cases occur in non-smokers, often due to EGFR mutations. Clinically, lung adenocarcinoma presents with chronic cough, hemoptysis, dyspnea, and pleuritic chest pain, and it has a high propensity for metastasis to the brain, liver, and bones.
- Colorectal adenocarcinoma develops in the glandular epithelium of the colon or rectum and is among the most frequently diagnosed cancers worldwide. The adenoma-carcinoma sequence, involving genetic alterations in APC, TP53, KRAS, and SMAD4, plays a critical role in tumor initiation and progression. Microsatellite instability (MSI), a hallmark of defective DNA mismatch repair, is a key molecular feature in a subset of cases. Risk factors include a diet high in red and processed meats, obesity, smoking, and chronic inflammatory bowel disease (IBD). Patients often present with hematochezia, altered bowel habits, abdominal pain, and anemia.
- Breast adenocarcinoma primarily originates in the ductal (invasive ductal carcinoma, IDC) or lobular (invasive lobular carcinoma, ILC) epithelium of the mammary glands. It is the most common malignancy in women, and its pathogenesis is closely linked to hormone receptor signaling (ER/PR positivity) and HER2 amplification. Genetic mutations, including BRCA1 and BRCA2, contribute to hereditary breast cancer syndromes. Clinically, breast adenocarcinoma may manifest as a palpable mass, skin dimpling, nipple retraction, or abnormal discharge. Early detection through mammography and molecular profiling has significantly improved survival rates.
- Prostate adenocarcinoma is the predominant malignancy of the male reproductive system, originating from the glandular epithelium of the prostate. It is often androgen-driven, with genetic alterations affecting TMPRSS2-ERG fusions, PTEN loss, and TP53 mutations. The disease typically progresses slowly, but aggressive forms can metastasize to the bone and lymph nodes. Symptoms include urinary hesitancy, nocturia, hematuria, and pelvic pain, but many cases remain asymptomatic in early stages, highlighting the importance of prostate-specific antigen (PSA) screening.
- Pancreatic adenocarcinoma, arising from pancreatic ductal epithelial cells, is one of the most lethal malignancies, with a five-year survival rate below 10%. It is frequently diagnosed at an advanced stage due to its aggressive biology and lack of early symptoms. Nearly 90% of cases harbor KRAS mutations, along with alterations in TP53, CDKN2A, and SMAD4. Patients often present with painless jaundice, weight loss, and epigastric pain, and metastatic spread is common at diagnosis. Currently, surgical resection and FOLFIRINOX chemotherapy remain the mainstay of treatment, though novel immunotherapies are under investigation.
- Esophageal adenocarcinoma typically arises in the distal esophagus, frequently in the setting of chronic gastroesophageal reflux disease (GERD) and Barrett’s esophagus, a precursor lesion characterized by intestinal metaplasia. Molecular alterations, including TP53 mutations and HER2 amplification, drive tumor progression. Patients often present with progressive dysphagia, odynophagia, retrosternal pain, and weight loss. Given its aggressive nature, early detection through endoscopic surveillance in high-risk individuals is critical for improving prognosis.
- Gastric adenocarcinoma originates in the glandular epithelium of the stomach and is strongly associated with Helicobacter pylori infection, which induces chronic inflammation, atrophic gastritis, and genetic mutations such as CDH1 loss in diffuse-type gastric cancer. Other risk factors include a diet high in salted and smoked foods, smoking, and Epstein-Barr virus (EBV) infection. Clinically, patients may experience epigastric pain, nausea, early satiety, and gastrointestinal bleeding. Molecular subtyping (MSI-high, EBV-positive, chromosomal instability, and genomically stable subtypes) has led to more personalized therapeutic strategies, including HER2-targeted and immune checkpoint inhibitors.
- Adenocarcinomas, despite their diverse organ origins, share common molecular pathways of tumorigenesis, immune evasion, and metastatic progression.
- Advances in genomic sequencing, biomarker-driven therapies, and immuno-oncology have improved the precision of treatment approaches. However, resistance mechanisms remain a major challenge, necessitating ongoing research into tumor microenvironment interactions, metabolic vulnerabilities, and novel combination therapies.
- As the landscape of cancer treatment continues to evolve, early detection, molecular profiling, and targeted therapeutic strategies will play a crucial role in improving patient outcomes.
