Cover image

The illustration evokes the spirit of exploration and discovery that underlies the study of molecular biology. Inspired by Alice in Wonderland, it reimagines a female scientist as Alice, standing before a keyhole that reveals a vibrant and intricate molecular world. The key in her hand symbolizes both the unlocking of scientific knowledge and the antibody–receptor interactions central to the biology of HER2-positive breast cancer and the therapeutic strategies explored in this study. In this issue, a complex landscape of HER2 transcript diversity generated by alternative splicing is unveiled—a regulatory mechanism that remains relatively underexplored in the context of therapeutic resistance. By integrating long- and short-read RNA sequencing, the study identifies dozens of HER2 isoforms with distinct structural features and subcellular localizations, some of which may evade recognition by currently available anti-HER2 antibody–drug conjugates (ADCs). This expanded isoform repertoire reveals novel mechanisms of drug resistance and underscores the importance of decoding splicing-driven proteomic diversity in the context of precision oncology.
The artwork was created by Alice Brassanini Mena Barreto dos Reis, a breast cancer survivor treated at the same institution where this research was conducted. One of the coauthors, Carlos H. dos Anjos, served as her clinical oncologist. This personal connection between the artist and the scientific team adds a powerful layer of meaning to the illustration—one that bridges science, healing, and artistic expression. (Cover art by Alice B.M.B. dos Reis, based on a concept by Alice B.M.B. dos Reis, Pedro A.F. Galante, Daniela P.Z. Galante, Gabriela D.A. Guardia, and Carlos H. dos Anjos. [For details, see Guardia et al., pp. 1942–1958.])