Steroidal derivatives in pancreatic cancer: Paving the way to new anticancer drugs

Pancreatic cancer remains one of the most life-threatening cancers worldwide with limited therapeutic options and a poor prognosis. Despite the advances in treatment regimens, the death rate of pancreatic cancer patients continues to rise, justifying the need for novel therapeutic agents. Steroidal derivatives, with their unique modifiable framework, have emerged as a promising class of compounds in drug discovery, namely for the search for novel anticancer drugs. A comprehensive review of studies on the anticancer activity of synthetic and natural steroidal derivatives for potential pancreatic cancer treatment was conducted, highlighting their structural versatility, mechanisms of action, and recent advances in their development. For this, an extensive literature search was conducted in two main databases - PubMed and Web of Science. In the preclinical setting, the steroidal derivatives described throughout this review display their cytotoxicity by different mechanisms, which culminate in cell death mostly by apoptosis. Remarkably, many of the pathways affected by this class of compounds are considered key players in many of the hallmarks of cancer, which reinforces the importance of studying steroidal derivatives for the treatment of pancreatic cancer. This review summarises the current state of research and underscores the potential of steroidal derivatives as a groundwork for novel therapeutic approaches in pancreatic cancer management, outlining future directions for their development as effective anticancer agents.