Migrastatic Agents, Metastasis, and Mitochondrial Metabolism: Emerging Strategies for Cancer Drug Discovery

Cancer remains one of the leading causes of death worldwide. Despite substantial progress in developing effective therapies over the past century, it remains a major challenge in biomedical research. Anticancer drug discovery has historically focused on cytotoxic compounds designed to selectively target cancer cells while minimizing harm to healthy tissue, with the primary objective of reducing primary tumor burden. However, metastasis is responsible for the majority of cancer-related deaths. This process has received comparatively less attention in anticancer drug development. Bridging this gap requires dedicated research strategies that move beyond cytotoxicity and address the underlying molecular mechanisms driving cancer cell migration, invasion, and secondary colonization.In recent years, the concept of migrastatic agents has been introduced to describe non-cytotoxic compounds that inhibit the steps of metastatic cascade. Within this framework, mitochondria have emerged as one of the most relevant therapeutic targets, given their central role in supplying the energetic and metabolic support required for cancer cell migration and invasion.Beyond ATP synthesis, mitochondria regulate calcium signaling, apoptosis, and reactive oxygen species (ROS) generation, processes that collectively govern cell motility and invasive behavior. Metastatic cells often exhibit metabolic flexibility, enabling rapid adaptation to the dynamic demands of the tumor microenvironment. This Research Topic aims to bring together current advances in the rational design of compounds targeting mitochondrial metabolism to disrupt metastatic progression, promoting molecular mechanisms/target validation for migrastatics, as a distinct therapeutic class in cancer drug discovery.This Research Topic welcomes contributions from researchers working at the intersection of medicinal chemistry, chemical biology, stromal-cancer communication, cancer metabolism and mitochondrial pharmacology. We invite original research articles, reviews, mini-reviews, perspectives, and hypothesis-and-theory manuscripts addressing, but not limited to, the following themes:• Synthesis and biological evaluation of migrastatic compounds targeting mitochondrial function• Mechanisms of mitochondrial adaptations that modulate cancer cell migration and invasion• Role of ROS, calcium signaling, and mitochondrial membrane potential in metastatic progression• Metabolic plasticity and substrate preferences of metastatic cells and its pharmacological exploitation• Computational approaches for the rational design of mitochondria-targeting antimetastatic agents• In vitro and in vivo models for preclinical assessment of migrastatic activity• Drug delivery strategies for mitochondria-directed antimetastatic compound Topic editors: Maximiliano Martínez-Cifuentes, Félix A. Urra, Pankaj Patyal Source: https://www.frontiersin.org/research-topics/82564/migrastatic-agents-metastasis-and-mitochondrial-metabolism-emerging-strategies-for-cancer-drug-discovery