The Dark Site of Conventional Cancer Therapy—Triggering the Origin of Recurrence Cancer Stem Cells

2016 ◽  
pp. 165-180
Keyword(s):  
Stem Cells ◽  
Cancer Therapy ◽  
Cancer Stem Cells

scholarly journals PIK3C3 Inhibition Promotes Sensitivity to Colon Cancer Therapy by Inhibiting Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2168
Author(s):  
Balawant Kumar ◽  
Rizwan Ahmad ◽  
Swagat Sharma ◽  
Saiprasad Gowrikumar ◽  
Mark Primeaux ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Side Population ◽  
Therapy Resistance ◽  
Fluorescent Reporter ◽  
Combination Treatments ◽  
Gsk 3Β ◽  
Resistance To Chemotherapy

Background: Despite recent advances in therapies, resistance to chemotherapy remains a critical problem in the clinical management of colorectal cancer (CRC). Cancer stem cells (CSCs) play a central role in therapy resistance. Thus, elimination of CSCs is crucial for effective CRC therapy; however, such strategies are limited. Autophagy promotes resistance to cancer therapy; however, whether autophagy protects CSCs to promote resistance to CRC-therapy is not well understood. Moreover, specific and potent autophagy inhibitors are warranted as clinical trials with hydroxychloroquine have not been successful. Methods: Colon cancer cells and tumoroids were used. Fluorescent reporter-based analysis of autophagy flux, spheroid and side population (SP) culture, and qPCR were done. We synthesized 36-077, a potent inhibitor of PIK3C3/VPS34 kinase, to inhibit autophagy. Combination treatments were done using 5-fluorouracil (5-FU) and 36-077. Results: The 5-FU treatment induced autophagy only in a subset of the treated colon cancer. These autophagy-enriched cells also showed increased expression of CSC markers. Co-treatment with 36-077 significantly improved efficacy of the 5-FU treatment. Mechanistic studies revealed that combination therapy inhibited GSK-3β/Wnt/β-catenin signaling to inhibit CSC population. Conclusion: Autophagy promotes resistance to CRC-therapy by specifically promoting GSK-3β/Wnt/β-catenin signaling to promote CSC survival, and 36-077, a PIK3C3/VPS34 inhibitor, helps promote efficacy of CRC therapy.

scholarly journals Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kristen Abernathy ◽  
Jeremy Burke
Keyword(s):  
Stem Cells ◽  
Glioblastoma Multiforme ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Differential Equations ◽  
Ordinary Differential Equations ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Common Event

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

Targeting pancreatic cancer stem cells for cancer therapy

2012 ◽  
Vol 1826 (2) ◽  
pp. 385-399 ◽  
Author(s):  
Jun Xia ◽  
Changjie Chen ◽  
Zhiwen Chen ◽  
Lucio Miele ◽  
Fazlul H. Sarkar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Pancreatic Cancer Stem Cells

scholarly journals Targeting self-renewal pathways in cancer stem cells: clinical implications for cancer therapy

Oncogenesis ◽  
2015 ◽  
Vol 4 (11) ◽  
pp. e177-e177 ◽  
Author(s):  
A Borah ◽  
S Raveendran ◽  
A Rochani ◽  
T Maekawa ◽  
D S Kumar
Keyword(s):  
Stem Cells ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Clinical Implications ◽  
Self Renewal
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