Emerging role of tumor cell plasticity in modifying therapeutic response

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Oct. 7, 2020

Abstract Resistance to cancer therapy is a major barrier management. Conventional views have proposed that acquisition of resistance may result from genetic mutations. However, accumulating evidence implicates key role non-mutational mechanisms underlying drug tolerance, the latter which focus will be discussed here. Such processes are largely driven by tumor cell plasticity, renders cells insusceptible drug-targeted pathway, thereby facilitating survival and growth. The concept plasticity highlights significance re-activation developmental programs closely correlated with epithelial–mesenchymal transition, properties stem cells, trans-differentiation potential during exposure. From observations in various cancers, this provides an opportunity for investigating nature anticancer resistance. Over years, our understanding emerging phenotype switching modifying therapeutic response has considerably increased. This expanded knowledge contributes developing novel strategies or combination regimens using available drugs, likely improve patient outcomes clinical practice.

Language: Английский

---

Sumoylation on its 25th anniversary: mechanisms, pathology, and emerging concepts

FEBS Journal, Journal Year: 2020, Volume and Issue: 287(15), P. 3110 - 3140

Published: April 7, 2020

Sumoylation is an essential post‐translational modification intimately involved in a diverse range of eukaryotic cellular mechanisms. Small ubiquitin‐like modifier (SUMO) protein isoforms can be reversibly linked to lysine residues that reside within specific motifs on thousands target substrates, leading modulations stability, solubility, localization, and interactor profile. Since its initial discovery almost 25 years ago, SUMO has been described as key regulator genomic cell proliferation, infection among other processes. In this review, we trace the exciting developments history critical modifier, highlighting SUMO’s roles pathogenesis well potential for development targeted therapies numerous diseases.

Language: Английский

---

Rational Cancer Treatment Combinations: An Urgent Clinical Need

Molecular Cell, Journal Year: 2020, Volume and Issue: 78(6), P. 1002 - 1018

Published: June 1, 2020

Language: Английский

---

Tumor biomarkers for diagnosis, prognosis and targeted therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Language: Английский

---

Cancer cell plasticity during tumor progression, metastasis and response to therapy

Nature Cancer, Journal Year: 2023, Volume and Issue: 4(8), P. 1063 - 1082

Published: Aug. 3, 2023

Language: Английский

---

Translational control of stem cell function

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(10), P. 671 - 690

Published: July 16, 2021

Language: Английский

---

Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy

Nature Chemical Biology, Journal Year: 2021, Volume and Issue: 17(5), P. 567 - 575

Published: March 4, 2021

Language: Английский

---

Hallmarks of cancer stemness

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(5), P. 617 - 639

Published: May 1, 2024

Language: Английский

---

The Transcriptional and Epigenetic Landscape of Cancer Cell Lineage Plasticity

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(8), P. 1771 - 1788

Published: July 20, 2023

Abstract Lineage plasticity, a process whereby cells change their phenotype to take on different molecular and/or histologic identity, is key driver of cancer progression and therapy resistance. Although underlying genetic changes within the tumor can enhance lineage it predominantly dynamic controlled by transcriptional epigenetic dysregulation. This review explores regulators plasticity interplay with other features malignancy, such as dysregulated metabolism, microenvironment, immune evasion. We also discuss strategies for detection treatment highly plastic tumors. Significance: hallmark critical facilitator oncogenic metastasis, resistance, It essential that mechanisms are elucidated enable development effectively target this phenomenon. In review, we describe cell in highlighting therapeutic approaches may be harnessed patient benefit.

Language: Английский

---

Understanding the impact of feedback regulations on blood cell production and leukemia dynamics using model analysis and simulation of clinically relevant scenarios

Applied Mathematical Modelling, Journal Year: 2024, Volume and Issue: 129, P. 340 - 389

Published: Feb. 4, 2024

Acute myeloid leukemia (AML) is a paradigmatic example of stem cell-driven cancer. AML belongs to the most aggressive malignancies and has poor prognosis. A hallmark expansion malignant cells in bone marrow out-competition healthy blood-forming (hematopoietic) cells. In present study, we develop nonlinear ordinary differential equation model study impact feedback configurations kinetic cell properties such as symmetric self-renewal probability, differentiation asymmetric division proliferation rate, or death rate on leukemic population dynamics. The accounts for two types (mature immature) (cells that can divide have lost ability divide). considered here generalization previous models contains them special case. We consider multiple differ their self-renewal, differentiation, probabilities. Linearized stability analysis performed derive necessary sufficient conditions extinction our analysis, distinguish three steady states, namely purely states (presence absence cells), composite where coexist. Steady-state reveals under biologically plausible assumptions are unique. If exist, they non-unique form one-dimensional manifold. state locally asymptotically stable if only unstable. analytical results illustrated by numerical simulations. Our suggest slight increase probability decrease compared destabilization homeostatic equilibrium This finding line with arrest observed Changes these parameters opposite direction re-establish population. furthermore suggests configuration loops impacts regeneration, growth cells, burden late stage leukemias decline patients.

Language: Английский

---