Designing precision medicine panels for drug refractory cancers targeting cancer stemness traits

Warrier, Sudha; Patil, Manasi; Bhansali, Sanyukta; Varier, Lavanya; Sethi, Gautam

doi:10.1016/j.bbcan.2020.188475

Cited by 19 publications

(8 citation statements)

References 99 publications

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“…[79][80][81][82][83][84] Beta-Catenin and Cancer Stem Cells Cancer stem cells (CSCs), also known as tumor-initiating cells, share similar features with normal stem cells, including self-renewal and differentiation capacities. 85,86 CSCs were first identified in acute myeloid leukemia and it was found that they can increase number of colony-formation capacitors. 87 CSCs are responsible for developing heterogenous feature of tumors and is in contrast with conventional belief that tumor heterogeneity is mediated by genetic and epigenetic alterations.…”

Section: Beta-catenin and Hepatocellular Carcinoma Beta-catenin Expression Status And Mutation: Clinical Associationmentioning

confidence: 99%

Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

Paskeh

Mirzaei

Ashrafizadeh

et al. 2021

JHC

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Section: Beta-catenin and Hepatocellular Carcinoma Beta-catenin Expression Status And Mutation: Clinical Associationmentioning

confidence: 99%

Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

Paskeh

Mirzaei

Ashrafizadeh

et al. 2021

JHC

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“…The incidence and mortality rates of leukemia tend to increase with age. Acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) have been noted to have bimodal age distributions, affecting both children and adults 56–59 . Sharma et al investigated pyrimethamine as a potent and selective inhibitor of AML, looking into its effect on MN1‐transformed leukemic cells.…”

Section: Antineoplastic Effects Of Pyrimethaminementioning

confidence: 99%

The multifaceted antineoplastic role of pyrimethamine against human malignancies

et al. 2022

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Cancer accounted for nearly 10 million deaths in 2020 and is the second leading cause of death worldwide. The chemotherapeutic agents that are in clinical practice possess a broad range of severe adverse effects towards vital organs which emphasizes the importance of the discovery of new therapeutic agents or repurposing of existing drugs for the treatment of human cancers. Pyrimethamine is an antiparasitic drug used for the treatment of malaria and toxoplasmosis with a well‐documented excellent safety profile. In the last 5 years, numerous efforts have been made to explore the anticancer potential of pyrimethamine in in vitro and in vivo preclinical models and to repurpose it as an anticancer agent. The studies have demonstrated that pyrimethamine inhibits oncogenic proteins such as STAT3, NF‐κB, DX2, MAPK, DHFR, thymidine phosphorylase, telomerase, and many more in a different types of cancer models. Moreover, pyrimethamine has been reported to work in synergy with other anticancer agents, such as temozolomide, to induce apoptosis of tumor cells. Recently, the results of phase‐1/2 clinical trials demonstrated that pyrimethamine administration reduces the expression of STAT3 signature genes in tumor tissues of chronic lymphocytic leukemia patients with a good therapeutic response. In the present article, we have reviewed most of the published articles related to the antitumor effects of pyrimethamine in malignancies of breast, liver, lung, skin, ovary, prostate, pituitary, and leukemia in in vitro and in vivo settings. We have also discussed the pharmacokinetic profile and results of clinical trials obtained after pyrimethamine treatment. From these studies, we believe that pyrimethamine has the potential to be repurposed as an anticancer drug.

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“…The CSCs are abundantly found in the tumor microenvironment and due to their self-renewal capacity, they can preserve population of tumor cells and mediating tumorigenesis. Besides, CSCs can differentiate into different cell kinds, enhancing cancer progression [ 61 , 62 ]. Overall, there are two concepts for carcinogenesis.…”

Section: Cancer Stem Cellsmentioning

confidence: 99%

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

Paskeh

Asadi²,

Zabolian

et al. 2021

IJMS

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As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/β-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.

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Designing precision medicine panels for drug refractory cancers targeting cancer stemness traits

Cited by 19 publications

References 99 publications

Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

The multifaceted antineoplastic role of pyrimethamine against human malignancies

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

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