Dark force rising: Reawakening and targeting of fetal-like stem cells in colorectal cancer
Sigrid K. Fey,
Nuria Vaquero-Siguero,
Rene Jackstadt
Affiliations
Sigrid K. Fey
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Cancer Progression and Metastasis Group, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany
Nuria Vaquero-Siguero
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Cancer Progression and Metastasis Group, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany
Rene Jackstadt
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Cancer Progression and Metastasis Group, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, 69120 Heidelberg, Germany; Corresponding author
Summary: Stem cells play pivotal roles in maintaining intestinal homeostasis, orchestrating regeneration, and in key steps of colorectal cancer (CRC) initiation and progression. Intriguingly, adult stem cells are reduced during many of these processes. On the contrary, primitive fetal programs, commonly detected in development, emerge during tissue repair, CRC metastasis, and therapy resistance. Recent findings indicate a dynamic continuum between adult and fetal stem cell programs. We discuss critical mechanisms facilitating the plasticity between stem cell states and highlight the heterogeneity observed upon the appearance of fetal-like states. We focus on therapeutic opportunities that arise by targeting fetal-like CRC cells and how those concepts can be translated into the clinic.