This graphical abstract illustrates the complex mechanisms of metastasis, emphasizing the contributions of genetic variation, post-transcriptional regulation, tumor metabolism, and the tumor microenvironment. It further explores the prospects of innovative therapeutic strategies, highlighting the demand for an integrative approach to address metastatic cancer effectively.

Cancer stem cells (CSCs) represent a fundamental barrier to effective cancer therapy, contributing to therapeutic resistance. Characterized by robust drug efflux capacity, enhanced DNA repair mechanisms, metabolic plasticity, resilience to oxidative stress, and upregulation of detoxifying ALDH enzymes, CSCs enable tumors to withstand various treatments. Recent studies indicate that therapeutic strategies targeting proliferative non-CSCs, directly eradicating CSCs, or inducing CSC differentiation may improve patient outcomes.

Ephrin A1 CAR targeting EphA2 exhibits potent cytotoxicity against EphA2-postive solid cancer cells in vitro and in vivo. Notably, no obvious toxic side effects were observed in mice and rhesus macaques.

1. Lomitapide can significantly inhibit the methyltransferase activity of METTL3 and reduce the m6A modification and expression of UQCC2. 2. The METTL3/UQCC2 axis inhibition by lomitapide could activate autophagy-mediated cell death, thus reversing osimertinib resistance in NSCLC cells.