Graphical AbstractWith DNA damage being a primary anti-cancertarget, a need has arisen for the development of an approach that is a harmlessfor normal tissues but allows for cancer cell-specific cytotoxicity. Previous researchfrom K. Gurova's suggests that small compounds, namely curaxins that bind theDNA can cause chromatin instability and cell death in a cancer cell-specificmanner. In this brief perspective commentary, we investigate how the scientificcommunity has further developed this anti-cancer approach.

Cancers often express hundreds of genes otherwise specific to germ cells, the germline/cancer (GC) genes. Here, we present and discuss the hypothesis that activation of a “germline program” promotes cancer cell malignancy. We do so by proposing four hallmark processes of the germline: meiosis, epigenetic plasticity, migration, and metabolic plasticity. Together, these hallmarks enable replicative immortality of germ cells as well as cancer cells. Especially meiotic genes are frequently expressed in cancer, implying that genes unique to meiosis may play a (...) role in oncogenesis. Because GC genes are not expressed in healthy somatic tissues, they form an appealing source of specific treatment targets with limited side effects besides infertility. Although it is still unclear why germ cell specific genes are so abundantly expressed in cancer, from our hypothesis it follows that the germline's reproductive program is intrinsic to cancer development. (shrink)