Reflections on drug resistance to KRAS inhibitors and gene silencing/editing tools for targeting mutant KRAS in cancer treatment.

KRAS is the most commonly mutated oncogene in human tumors, especially in lung, pancreatic, and colorectal cancers. Small-molecule inhibitors targeting mutant KRAS demonstrated promising anti-tumor effect in patients with non-small cell lung cancer harboring KRAS mutation, while the intrinsic and acquired drug resistance occurred frequently and might be inevitable. Unlike the protein-level inhibition approach, gene silencing/editing tools for DNA-level knockout and RNA-level knockdown of mutant KRAS may be advantageous since these approaches directly eliminate the production of mutant KRAS-encoded protein.

Novel D323G mutation of DSG4 gene in a girl with localized autosomal recessive hypotrichosis clinically overlapped with monilethrix.

Background: Localized autosomal recessive hypotrichosis (LAH) is an inherited rare disease caused by DSG4 mutations, characterized by short, sparse, brittle hair affecting restricted areas such as the scalp, trunk, and extremities. To date, DSG4 mutations have been reported in 14 pedigrees of LAH overlapping with monilethrix.

Methods: To clarify the etiology of hair defects for a 2-year-old Chinese girl, peripheral blood, skin, and hair samples were collected, and skin immunohistochemistry, electron microscopy (scanning and transmission types), Vivascope confocal microscopy, and DSG4 sequencing were investigated.