Targeting colorectal cancer (stem-like) cells using LGR5 directed antibody drug conjugates

Tumors are comprised of phenotypically and genotypically heterogeneous cell populations. The stem cell hypothesis of cancer proposes that tumors are organized hierarchically, in analogy to many normal organs and tissues that are renewed and maintained by adult tissue specific stem cells; in other words, a subpopulation of tumor cells possesses stem cell-like capabilities, hence being able to self-renew and to generate the diverse cells that comprise the bulk of the tumor. It is thought that so-called ‘cancer stem cells’ are involved in tumor relapse, metastasis and therapeutic resistance. Consequently, pursuing stem cells as therapeutic targets represents an interesting approach and might help to overcome some of the frustrations associated with current cancer treatment regimens. However, most cancer stem cell markers, often cell surface molecules, are not restricted to cancer cells but are also expressed in normal stem cells, making the selective targeting of cancer stem cells without harming normal tissue and organ function a challenge.