Cancer stem cells: advances in biology and clinical translation—a Keystone Symposia report

Abstract

The test for the cancer stem cell (CSC) hypothesis is to find a target expressed on all, and only CSCs in a patient tumor, then eliminate all cells with that target that eliminates the cancer. That test has not yet been achieved, but CSC diagnostics and targets found on CSCs and some other cells have resulted in a few clinically relevant therapies. However, it has become apparent that eliminating the subset of tumor cells characterized by self‐renewal properties is essential for long‐term tumor control. CSCs are able to regenerate and initiate tumor growth, recapitulating the heterogeneity present in the tumor before treatment. As great progress has been made in identifying and elucidating the biology of CSCs as well as their interactions with the tumor microenvironment, the time seems ripe for novel therapeutic strategies that target CSCs to find clinical applicability. On May 19–21, 2021, researchers in cancer stem cells met virtually for the Keystone eSymposium “Cancer Stem Cells: Advances in Biology and Clinical Translation” to discuss recent advances in the understanding of CSCs as well as clinical efforts to target these populations.

CD98 heavy chain as a prognostic biomarker and target for cancer treatment

“…Some CSC populations are also proven to be resistant to the conventional treatment ( 128 , 130 , 131 ). CSC markers were related to the poor clinical prognosis in different types of cancer ( 124 , 128 , 132 , 133 ). CD98hc and CD98hc-binding proteins, such as SLC7A5 and SLC7A11, have been characterized as putative CSC markers for several malignancies ( 134 – 138 ) ( Table 2 ).…”

Imagine beyond: recent breakthroughs and next challenges in mammary gland biology and breast cancer research

“…It is important to realize that the same molecular and cellular properties thought to underlie MRD and dormancy can be applied to the concept of cancer stem cells (CSCs). While their role and identity also still remain poorly understood [ 144 , 145 ], cells with properties of stem cells can resist current forms of therapy, including radiation [ 146 ], chemotherapy [ 147 ] and hormone therapy [ 148 ], facilitating development of tumor recurrence. While it is currently unclear how far MRD and dormancy should be interpreted in this context, as always it is important to let biological understanding and not semantics drive the discussion.…”

Cancer Stem Cells and Prostate Cancer: A Narrative Review

“…The CSC model hypothesis explains tumor heterogeneity, initiating ability, and therapeutic resistance [13]. In addition, a small number of CSCs are needed to recapitulate the tumor and its initial heterogeneity [13].…”

“…The CSC model hypothesis explains tumor heterogeneity, initiating ability, and therapeutic resistance [13]. In addition, a small number of CSCs are needed to recapitulate the tumor and its initial heterogeneity [13]. Cancer cells are organized in hierarchical order and CSCs stem on top of the pyramid, having stem-like characteristics such as self-renewal, pluripotency, and plasticity, that evolve during the lifetime of a tumor [14].…”

“…Cancer cells are organized in hierarchical order and CSCs stem on top of the pyramid, having stem-like characteristics such as self-renewal, pluripotency, and plasticity, that evolve during the lifetime of a tumor [14]. CSCs may be involved in PCa development and may solve the unmet needs in PCa prevention and diagnosis [13]. Their possible role in PCa progression may also improve the current gaps in PCa treatment, especially in the castration-resistant stages of the disease when androgen sensitivity is compromised [15].…”