Molecular mechanisms associated with chemoresistance in esophageal cancer

• Published in: Cellular and molecular life sciences : CMLS 2022-02, Vol.79 (2), p.116, Article 116
• Main Authors: Lohan-Codeço, Matheus, Barambo-Wagner, Maria Luísa, Nasciutti, Luiz Eurico, Ribeiro Pinto, Luis Felipe, Meireles Da Costa, Nathalia, Palumbo, Antonio
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Antineoplastic Agents - therapeutic use; Apoptosis; Autophagy; Biochemistry; Biomarkers, Tumor - antagonists & inhibitors; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer; Carboplatin; Carboplatin - therapeutic use; Cell Biology; Cell cycle; Chemical compounds; Chemoresistance; Chemotherapy; Cisplatin; Cisplatin - therapeutic use; Deregulation; Disease management; Drug metabolism; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Epigenetics; Esophageal cancer; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophagus; Fluorouracil - therapeutic use; Humans; Life Sciences; Malignancy; Metabolism; Metastases; Molecular modelling; Molecular Targeted Therapy - methods; Mutation; Paclitaxel; Paclitaxel - therapeutic use; Pharmacology; Review; Stem cells; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumor Microenvironment - genetics; Tumors
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-022-04131-6

Esophageal cancer (EC) is one of the most incident and lethal tumors worldwide. Although surgical resection is an important approach in EC treatment, late diagnosis, metastasis and recurrence after surgery have led to the management of adjuvant and neoadjuvant therapies over the past few decades. In this scenario, 5-fluorouracil (5-FU) and cisplatin (CISP), and more recently paclitaxel (PTX) and carboplatin (CBP), have been traditionally used in EC treatment. However, chemoresistance to these agents along EC therapeutic management represents the main obstacle to successfully treat this malignancy. In this sense, despite the fact that most of chemotherapy drugs were discovered several decades ago, in many cases, including EC, they still represent the most affordable and widely employed treatment approach for these tumors. Therefore, this review summarizes the main mechanisms through which the response to the most widely chemotherapeutic agents used in EC treatment is impaired, such as drug metabolism, apoptosis resistance, cancer stem cells (CSCs), cell cycle, autophagy, energetic metabolism deregulation, tumor microenvironment and epigenetic modifications.