Cancer Treatment with Gene Therapy and Radiation Therapy

Kaliberov, Sergey A.; Buchsbaum, Donald J.

doi:10.1016/b978-0-12-398342-8.00007-0

Cited by 72 publications

(45 citation statements)

References 178 publications

(181 reference statements)

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“…5-FC, but not 5-FU, is able to diffuse through blood brain barrier; hence, many studies have focused on using this property for treating hard-to-reach tumors such as glioblastoma [87]. The other advantage of CD/5-FC system is the radiosensitizing ability of 5-FU which can enhance its tumor killing efficiency in combination with radiotherapy [88]. It is feasible to detect the conversion of 5-FC to 5-FU in patients using fluorine magnetic resonance spectroscopy ( 19 F MRS) and fluorine magnetic resonance spectroscopic imaging ( 19 F MRSI) which makes the system suitable for clinical translation [89].…”

Section: Enzyme/prodrug Systems: From Bench To Bedmentioning

confidence: 99%

Progress and problems with the use of suicide genes for targeted cancer therapy

Karjoo

Chen

Hatefi

2016

Advanced Drug Delivery Reviews

156

168

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Among various gene therapy methods for cancer, suicide gene therapy attracts a special attention because it allows selective conversion of non-toxic compounds into cytotoxic drugs inside cancer cells. As a result, therapeutic index can be increased significantly by introducing high concentrations of cytotoxic molecules to the tumor environment while minimizing impact on normal tissues. Despite significant success at the preclinical level, no cancer suicide gene therapy protocol has delivered the desirable clinical significance yet. This review gives a critical look at the six main enzyme/prodrug systems that are used in suicide gene therapy of cancer and familiarizes readers with the state-of-the-art research and practices in this field. For each enzyme/prodrug system, the mechanisms of action, protein engineering strategies to enhance enzyme stability/affinity and chemical modification techniques to increase prodrug kinetics and potency are discussed. In each category, major clinical trials that have been performed in the past decade with each enzyme/prodrug system are discussed to highlight the progress to date. Finally, shortcomings are underlined and areas that need improvement in order to produce clinical significance are delineated.

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Section: Enzyme/prodrug Systems: From Bench To Bedmentioning

confidence: 99%

Progress and problems with the use of suicide genes for targeted cancer therapy

Karjoo

Chen

Hatefi

2016

Advanced Drug Delivery Reviews

156

168

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“…Ovarian cancer and pancreatic cancer are threatening tumors with the high prevalence and the high clinical mortality, which are cured mainly by surgical treatment . Chemotherapy plays a supplementary role in the procedure, it helps to kill cancer cells in co‐operation and in another way assists to improve patients’ life quality . ERS is a subcellular pathological process of misbalance in ER homeostasis and physical function disorder.…”

Section: Disscusionmentioning

confidence: 99%

Cucurbitacin I induces cancer cell death through the endoplasmic reticulum stress pathway

Chen

et al. 2018

J of Cellular Biochemistry

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Endoplasmic reticulum stress (ERS) is usually involved in tumor development and progression, and anticancer agents have recently been recognized to induce ERS. Cucurbitacin‐I showed a potent anticancer action by inducing apoptosis through the inhibition of signal transducer and activator of transcription 3 pathway and triggering autophagic cell death. It is not known whether ERS mediates the cancer cell death induced by cucurbitacin‐I. Here, we investigated the role of ERS in cucurbitacin‐I‐treated SKOV3 ovarian cancer cells and PANC‐1 pancreatic cancer cells. We confirmed that cucurbitacin‐I caused cell death and stirred excessive ERS levels by activating inositol requiring enzyme 1α (IRE1α) and protein kinase R‐like endoplasmic reticulum kinase (PERK), as well as PERK downstream factors, including IRE1α and C/EBP homologous protein, but not activating transcription factor 6 (ATF6α) pathway, which was in parallel with the increased Bax and caspase‐12‐dependent ERS‐associated apoptosis, autophagy and autophagy flux levels and caspase‐independent nonapoptotic cell death. Furthermore, 4‐phenylbutyrate, an ERS inhibitor, suppressed cucurbitacin‐I‐induced apoptosis, autophagy, autophagy flux, and autophagic cell death. Simultaneously, there are positive correlations among ERS and cucurbitacin‐I‐induced reactive oxygen species and Ca 2+. Our results suggested that cucurbitacin‐I‐induced cancer cell death through the excessive ERS and CHOP‐Bax and caspase‐12‐dependent ERS‐associated apoptosis, as well as ERS‐dependent autophagy, autophagy flux, and caspase‐independent nonapoptotic cell death. These novel signaling insights may be useful for developing new, effective anticancer strategies in oncotherapy.

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“…Although cancer cells proliferate more quickly than normal cells, leaving their DNA more susceptible to unrepaired damage, these cells often contain multiple mutations resulting in constitutive activation of mechanisms for DNA repair or allowing them to survive following damage that would render normal cells unviable [34]. …”

Section: Ionizing Radiation-induced Cell Toxicitiesmentioning

confidence: 99%

“…Some cell types rapidly undergo apoptosis in response to the same level of radiation that induces senescence in another cell type (e.g., primary human hematopoietic CD34 + cells undergo apoptosis whereas pulmonary artery endothelial cells primarily undergo accelerated senescence) [27,37]. The selection process resulting in a specific mode of cell death or senescence has not been clearly defined, but research indicates that it is affected by the radiation dose, the dose rate, and multiple aspects of the cellular context [31,32,34,38,39]. …”

Section: Ionizing Radiation-induced Cell Toxicitiesmentioning

confidence: 99%

Mechanisms of Radiation Toxicity in Transformed and Non-Transformed Cells

Panganiban

Snow

Day

2013

IJMS

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Radiation damage to biological systems is determined by the type of radiation, the total dosage of exposure, the dose rate, and the region of the body exposed. Three modes of cell death—necrosis, apoptosis, and autophagy—as well as accelerated senescence have been demonstrated to occur in vitro and in vivo in response to radiation in cancer cells as well as in normal cells. The basis for cellular selection for each mode depends on various factors including the specific cell type involved, the dose of radiation absorbed by the cell, and whether it is proliferating and/or transformed. Here we review the signaling mechanisms activated by radiation for the induction of toxicity in transformed and normal cells. Understanding the molecular mechanisms of radiation toxicity is critical for the development of radiation countermeasures as well as for the improvement of clinical radiation in cancer treatment.

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Cancer Treatment with Gene Therapy and Radiation Therapy

Cited by 72 publications

References 178 publications

Progress and problems with the use of suicide genes for targeted cancer therapy

Progress and problems with the use of suicide genes for targeted cancer therapy

Cucurbitacin I induces cancer cell death through the endoplasmic reticulum stress pathway

Mechanisms of Radiation Toxicity in Transformed and Non-Transformed Cells

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