Applications of high-resolution clone tracking technologies in cancer

Morgan, Don W.; Jost, Tyler A.; Santiago, Carolina De; Brock, Amy

doi:10.1016/j.cobme.2021.100317

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…Another useful tool for furthering our understanding of resistance evolution is clonal tracing. This experimental method can be used to examine the evolutionary dynamics of evolving cells by inserting heritable barcode tags in individual cells within a starting population and characterizing phenotypic changes in the subpopulations that arise from different clones [ 74 ]. Such phenotypes could include changes in the transcriptome, proteome, and drug responses.…”

Section: Predicting Drug Sensitivity To Improve Treatment Planningmentioning

confidence: 99%

Evolution-Informed Strategies for Combating Drug Resistance in Cancer

Lin‐Rahardja

Weaver

Scarborough

et al. 2023

IJMS

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The ever-changing nature of cancer poses the most difficult challenge oncologists face today. Cancer’s remarkable adaptability has inspired many to work toward understanding the evolutionary dynamics that underlie this disease in hopes of learning new ways to fight it. Eco-evolutionary dynamics of a tumor are not accounted for in most standard treatment regimens, but exploiting them would help us combat treatment-resistant effectively. Here, we outline several notable efforts to exploit these dynamics and circumvent drug resistance in cancer.

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Section: Predicting Drug Sensitivity To Improve Treatment Planningmentioning

confidence: 99%

Evolution-Informed Strategies for Combating Drug Resistance in Cancer

Lin‐Rahardja

Weaver

Scarborough

et al. 2023

IJMS

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“…We suggest using mathematical modeling to examine how best to leverage each of these two approaches to gain information on the cancer of interest. In addition, emerging clone-tracking technology allows for ever more in-depth study of tumor evolution ( Morgan et al, 2021 ). Mathematical modeling will be a useful tool in designing, and interpreting results from, clone-tracking experiments ( Acar et al, 2020 ; Damaghi et al, 2021 ; Johnson et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

A survey of open questions in adaptive therapy: Bridging mathematics and clinical translation

West

Adler

Gallaher

et al. 2023

eLife

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Adaptive therapy is a dynamic cancer treatment protocol that updates (or ‘adapts’) treatment decisions in anticipation of evolving tumor dynamics. This broad term encompasses many possible dynamic treatment protocols of patient-specific dose modulation or dose timing. Adaptive therapy maintains high levels of tumor burden to benefit from the competitive suppression of treatment-sensitive subpopulations on treatment-resistant subpopulations. This evolution-based approach to cancer treatment has been integrated into several ongoing or planned clinical trials, including treatment of metastatic castrate resistant prostate cancer, ovarian cancer, and BRAF-mutant melanoma. In the previous few decades, experimental and clinical investigation of adaptive therapy has progressed synergistically with mathematical and computational modeling. In this work, we discuss 11 open questions in cancer adaptive therapy mathematical modeling. The questions are split into three sections: (1) integrating the appropriate components into mathematical models (2) design and validation of dosing protocols, and (3) challenges and opportunities in clinical translation.

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“…While incredibly useful, pseudotime trajectories do not allow for the pinpointing of the populations critical for these tumor dynamics, rather phenotypic characteristics are inferred from the populations identified in the screening. In recent years, genetic barcode lineage tracing has emerged as a novel tool to trace individual clonal populations over time (31)(32)(33). Genetic barcode lineage tracing allows for the identification of individual cellular clones by inserting a unique piece of DNA to serve as a "barcode" in the genome of a cell using a retrovirus or CRISPR sgRNA library (28,34,35).…”

Section: Introductionmentioning

confidence: 99%

Single Cell lineage Tracing Identifies Cancer Testis Antigens as Mediators of Chemoresistance in Small Cell Lung Cancer

Wollenzien

Tecleab

Szczepaniak-Sloane

et al. 2022

Preprint

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Small Cell Lung Cancer (SCLC) is often a heterogeneous tumor, where dynamic regulation of key transcription factors can drive multiple populations of phenotypically different cells which contribute differentially to tumor dynamics. This tumor is characterized by a very low 2-year survival rate, high rates of metastasis, and rapid acquisition of chemoresistance. The heterogeneous nature of this tumor makes it difficult to study and to treat, as it is not clear how or when this heterogeneity arises. Here we describe temporal, single-cell analysis of SCLC to investigate tumor initiation and chemoresistance in both SCLC xenografts andin situSCLC mouse models. We identify an early population of tumor cells with high expression of AP-1 network genes that are critical for tumor growth. Furthermore, we have identified and validated the cancer testis antigens (CTAs) PAGE5 and GAGE2A as mediators of chemoresistance in human SCLC. CTAs have successfully been targeted in other tumor types and may be a promising avenue for targeted therapy in SCLC.

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Applications of high-resolution clone tracking technologies in cancer

Cited by 5 publications

References 49 publications

Evolution-Informed Strategies for Combating Drug Resistance in Cancer

Evolution-Informed Strategies for Combating Drug Resistance in Cancer

A survey of open questions in adaptive therapy: Bridging mathematics and clinical translation

Single Cell lineage Tracing Identifies Cancer Testis Antigens as Mediators of Chemoresistance in Small Cell Lung Cancer

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