Induced Phenotype Targeted Therapy: Radiation-Induced Apoptosis-Targeted Chemotherapy

Lee, Beom Suk; Cho, Yong Woo; Kim, Gui Chul; Lee, Do Hee; Kim, Chang‐Jin; Kil, Hee Seup; Yoon, Dae Hwan; Byun, Youngro; Yuk, Soon Hong; Kim, Kwangmeyung; Kim, In San; Kwon, Ick Chan; Kim, Sang Yoon

doi:10.1093/jnci/dju403

Cited by 60 publications

(55 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Enhanced apoptosis is one of the key anti-tumor responses mediated by EphB4 targeting and radiation325262728. In caspase-3/7 assay, we observed a significant increase in apoptosis (~28%) in Fadu cells transfected with EphB4-siRNA and 4 Gy dose of radiation compared to radiation alone at 96 h (Fig.…”

Section: Resultsmentioning

confidence: 71%

See 1 more Smart Citation

Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

Sharma

Oweida

Griego

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Members of the Eph family of receptor tyrosine kinases have been implicated in a wide array of human cancers. The EphB4 receptor is ubiquitously expressed in head and neck squamous cell carcinoma (HNSCC) and has been shown to impart tumorigenic and invasive characteristics to these cancers. In this study, we investigated whether EphB4 receptor targeting can enhance the radiosensitization of HNSCC. Our data show that EphB4 is expressed at high to moderate levels in HNSCC cell lines and patient-derived xenograft (PDX) tumors. We observed decreased survival fractions in HNSCC cells following EphB4 knockdown in clonogenic assays. An enhanced G2 cell cycle arrest with activation of DNA damage response pathway and increased apoptosis was evident in HNSCC cells following combined EphB4 downregulation and radiation compared to EphB4 knockdown and radiation alone. Data using HNSCC PDX models showed significant reduction in tumor volume and enhanced delay in tumor regrowth following sEphB4-HSA administration with radiation compared to single agent treatment. sEphB4-HSA is a protein known to block the interaction between the EphB4 receptor and its ephrin-B2 ligand. Overall, our findings emphasize the therapeutic relevance of EphB4 targeting as a radiosensitizer that can be exploited for the treatment of human head and neck carcinomas.

show abstract

Section: Resultsmentioning

confidence: 71%

“…Previous studies have found a correlation between radiation and programmed cell death27284445. Importantly, EphB4 knockdown has been reported to promote cell death by apoptosis339.…”

Section: Discussionmentioning

confidence: 97%

Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

Sharma

Oweida

Griego

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Kim and co-workers recently developed an induced phenotype targeted therapy (IPTT) where DEVD-S-DOX prodrug containing DOX linked to a peptide moiety (DEVD) is cleaved by an enzyme caspase-3. Caspase three expression is elevated in tumor region by radiation induced apoptosis [196]. Several enzyme cleavable peptide prodrug conjugates and formulations of DOX have been recently developed to increase the specificity and tolerability of chemotherapeutic agents [197–205].…”

Section: Prodrug Approach: Analog / Chemical Conjugation For Cancementioning

confidence: 99%

Novel delivery approaches for cancer therapeutics

Mitra

Agrahari

Mandal

et al. 2015

Journal of Controlled Release

138

View full text Add to dashboard Cite

Currently, a majority of cancer treatment strategies are based on the removal of tumor mass mainly by surgery. Chemical and physical treatments such as chemo- and radiotherapies have also made a major contribution in inhibiting rapid growth of malignant cells. Furthermore, these approaches are often combined to enhance therapeutic indices. It is widely known that surgery, chemo- and radiotherapy also inhibit normal cells growth. In addition, these treatment modalities are associated with severe side effects and high toxicity which in turn lead to low quality of life. This review encompasses novel strategies for more effective chemotherapeutic delivery aiming to generate better prognosis. Currently, cancer treatment is a highly dynamic field and significant advances are being made in the development of novel cancer treatment strategies. In contrast to conventional cancer therapeutics, novel approaches such as ligand or receptor based targeting, triggered release, intracellular drug targeting, gene delivery, cancer stem cell therapy, magnetic drug targeting and ultrasound-mediated drug delivery, have added new modalities for cancer treatment. These approaches have led to selective detection of malignant cells leading to their eradication with minimal side effects. Lowering, multi-drug resistance and involving influx transportation in targeted drug delivery to cancer cells can also contribute significantly in the therapeutic interventions in cancer.

show abstract

“…Lee et al described a novel strategy called induced phenotype targeted therapy to simplify targets complicated by tumor heterogeneity and to overcome tumor evolutionary complexity [20]. In this strategy, a specific apoptotic phenotype was artificially induced and used as a target for prodrugs.…”

Section: Magnified Viewmentioning

confidence: 99%

Neoantigen activation, Protein Translocation and Targeted Drug Delivery in Combination With Radiotherapy

Sethuraman

Ranjan

2016

Ther. Deliv.

View full text Add to dashboard Cite

Concurrent chemo and radiation therapies are commonly used to treat locally advanced cancer. Despite improved efficacy, failure rates remain high due to healthy organ toxicity caused by chemo-radiotherapy. Recent technological advances such as nanoparticle encapsulation of anticancer agents, locally controlled irradiation and concurrent use of radio- and nano-medicines are providing innovative solutions for overcoming the limitations of systemic and local treatment toxicities. In this mini-review, we discuss the roles of radiotherapy in generating new therapeutic targets and altering the tumor microenvironment, and we propose their future applications in drug delivery in combination with radiotherapy.

show abstract

Induced Phenotype Targeted Therapy: Radiation-Induced Apoptosis-Targeted Chemotherapy

Abstract: Such a phenotype induction strategy represents a conceptually novel approach to overcome tumor heterogeneity and complexity as well as to substantially improve current conventional chemoradiotherapy with fewer sequelae and side effects.

Cited by 60 publications

References 33 publications

Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

Novel delivery approaches for cancer therapeutics

Neoantigen activation, Protein Translocation and Targeted Drug Delivery in Combination With Radiotherapy

Contact Info

Product

Resources

About