Novel treatment strategies for malignant gliomas using neural stem cells

Introduction of tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myelogenous leukemia (CML), and treatment-free remission (TFR) is now a treatment goal. However, about half of the patients experience molecular relapse after cessation of TKIs, suggesting that leukemic stem cells (LSCs) are resistant to TKIs. Eradication of the remaining LSCs using immunotherapies including interferon-alpha, vaccinations, CAR-T cells, and other drugs would be a key strategy to achieve TFR.

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Adult Neurogenesis and Glial Oncogenesis: When the Process Fails

BioMed Research International ◽

10.1155/2014/438639 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Chary Marquez Batista ◽

Eric Domingos Mariano ◽

Breno José Alencar Pires Barbosa ◽

Matthias Morgalla ◽

Suely Kazue Nagahashi Marie ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Tumor Growth ◽

Cell Biology ◽

Treatment Strategies ◽

Tumor Formation ◽

Glial Tumor ◽

Novel Treatment ◽

Novel Treatment Strategies ◽

High Degree

Malignant brain tumors, including glioblastoma multiforme (GBM), are known for their high degree of invasiveness, aggressiveness, and lethality. These tumors are made up of heterogeneous cell populations and only a small part of these cells (known as cancer stem cells) is responsible for the initiation and recurrence of the tumor. The biology of cancer stem cells and their role in brain tumor growth and therapeutic resistance has been extensively investigated. Recent work suggests that glial tumors arise from neural stem cells that undergo a defective process of differentiation. The understanding of this process might permit the development of novel treatment strategies targeting cancer stem cells. In the present review, we address the mechanisms underlying glial tumor formation, paying special attention to cancer stem cells and the role of the microenvironment in preserving them and promoting tumor growth. Recent advancements in cancer stem cell biology, especially regarding tumor initiation and resistance to chemo- or radiotherapy, have led to the development of novel treatment strategies that focus on the niche of the stem cells that make up the tumor. Encouraging results from preclinical studies predict that these findings will be translated into the clinical field in the near future.

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Therapeutic Targeting Strategies of Cancer Stem Cells in Gastrointestinal Malignancies

Biomedicines ◽

10.3390/biomedicines7010017 ◽

2019 ◽

Vol 7 (1) ◽

pp. 17 ◽

Cited By ~ 9

Author(s):

Mohamad Sonbol ◽

Daniel Ahn ◽

Tanios Bekaii-Saab

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Treatment Strategies ◽

Treatment Resistance ◽

Cancer Growth ◽

Distinct Population ◽

Therapeutic Targeting ◽

Gastrointestinal Malignancies ◽

Novel Treatment ◽

Novel Treatment Strategies

Cancer stem cells (CSCs) are thought to be a distinct population of cells within a tumor mass that are capable of asymmetric division and known to have chemoresistant characteristics. The description and identification of CSC models in cancer growth and recurrence has inspired the design of novel treatment strategies to overcome treatment resistance by targeting both CSCs and non-CSC tumor cells. Several cellular signaling pathways have been described as playing a role in the induction and maintenance of stemness in CSCs, such as the Wnt/β-catenin, Notch, STAT3, and Hedgehog pathways. In this review, we aim to review some of the ongoing CSC therapeutic targeting strategies in gastrointestinal malignancies.

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Unique Genomic Landscape of High-Grade Neuroendocrine Cervical Carcinoma: Implications for Rethinking Current Treatment Paradigms

JCO Precision Oncology ◽

10.1200/po.19.00248 ◽

2020 ◽

pp. 972-987

Author(s):

Ramez N. Eskander ◽

Julia Elvin ◽

Laurie Gay ◽

Jeffrey S. Ross ◽

Vincent A. Miller ◽

...

Keyword(s):

Treatment Strategies ◽

Current Treatment ◽

High Grade ◽

Novel Treatment ◽

Sample Average ◽

Genomic Landscape ◽

Comprehensive Genomic Profiling ◽

Tumor Mutational Burden ◽

Sample Range ◽

Novel Treatment Strategies

PURPOSE High-grade neuroendocrine cervical cancer (HGNECC) is an uncommon malignancy with limited therapeutic options; treatment is patterned after the histologically similar small-cell lung cancer (SCLC). To better understand HGNECC biology, we report its genomic landscape. PATIENTS AND METHODS Ninety-seven patients with HGNECC underwent comprehensive genomic profiling (182-315 genes). These results were subsequently compared with a cohort of 1,800 SCLCs. RESULTS The median age of patients with HGNECC was 40.5 years; 83 patients (85.6%) harbored high-risk human papillomavirus (HPV). Overall, 294 genomic alterations (GAs) were identified (median, 2 GAs/sample; average, 3.0 GAs/sample, range, 0-25 GAs/sample) in 109 distinct genes. The most frequently altered genes were PIK3CA (19.6% of cohort), MYC (15.5%), TP53 (15.5%), and PTEN (14.4%). RB1 GAs occurred in 4% versus 32% of HPV-positive versus HPV-negative tumors ( P < .0001). GAs in HGNECC involved the following pathways: PI3K/AKT/mTOR (41.2%); RAS/MEK (11.3%); homologous recombination (9.3%); and ERBB (7.2%). Two tumors (2.1%) had high tumor mutational burden (TMB; both with MSH2 alterations); 16 (16.5%) had intermediate TMB. Seventy-one patients (73%) had ≥ 1 alteration that was theoretically druggable. Comparing HGNECC with SCLC, significant differences in TMB, microsatellite instability, HPV-positive status, and in PIK3CA, MYC, PTEN, TP53, ARID1A, and RB1 alteration rates were found. CONCLUSION This large cohort of patients with HGNECC demonstrated a genomic landscape distinct from SCLC, calling into question the biologic and therapeutic relevance of the histologic similarities between the entities. Furthermore, 73% of HGNECC tumors had potentially actionable alterations, suggesting novel treatment strategies for this aggressive malignancy.

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