Currently, therapeutic interventions targeting simultaneous inhibition of MEK/extracellular signal-regulated kinase (ERK) and PI3K/AKT signaling with the aim to overcome drug resistance mediated by upstream mutations of Ras and/or Raf are tested in advanced PC carrying K-Ras, N-Ras, and/or B-Raf mutations. Here, KRAS is linked to pachyonychia congenita.