The development of MDA-7/IL-24 as a cancer therapeutic

Paul Dent; Adly Yacoub; Hossein A. Hamed; Margaret A. Park; Rupesh Dash; Sujit K. Bhutia; Devanand Sarkar; Xiang Yang Wang; Pankaj Gupta; Luni Emdad; Irina V. Lebedeva; Moira Sauane; Zhao zhong Su; Mohamed Rahmani; William C. Broaddus; Harold F. Young; Maciej S. Lesniak; Steven Grant; David T. Curiel; Paul B. Fisher

doi:10.1016/j.pharmthera.2010.08.001

The development of MDA-7/IL-24 as a cancer therapeutic

Paul Dent, Adly Yacoub, Hossein A. Hamed, Margaret A. Park, Rupesh Dash, Sujit K. Bhutia, Devanand Sarkar, Xiang Yang Wang, Pankaj Gupta, Luni Emdad, Irina V. Lebedeva, Moira Sauane, Zhao zhong Su, Mohamed Rahmani, William C. Broaddus, Harold F. Young, Maciej S. Lesniak, Steven Grant, David T. Curiel, Paul B. Fisher

Medicine - Veteran's Administration Medical Center

Research output: Contribution to journal › Review article › peer-review

53 Scopus citations

Abstract

The cytokine melanoma differentiation associated gene 7 (mda-7) was identified by subtractive hybridization as a protein whose expression increased during the induction of terminal differentiation, and that was either not expressed or was present at low levels in tumor cells compared to non-transformed cells. Based on conserved structure, chromosomal location and cytokine-like properties, MDA-7, was classified as a member of the interleukin (IL)-10 gene family and designated as MDA-7/IL-24. Multiple studies have demonstrated that expression of MDA-7/IL-24 in a wide variety of tumor cell types, but not in corresponding equivalent non-transformed cells, causes their growth arrest and rapid cell death. In addition, MDA-7/IL-24 has been noted to radiosensitize tumor cells which in part is due to the generation of reactive oxygen species (ROS) and ceramide that cause endoplasmic reticulum stress and suppress protein translation. Phase I clinical trial data has shown that a recombinant adenovirus expressing MDA-7/IL-24 (Ad.mda-7 (INGN-241)) was safe and had measurable tumoricidal effects in over 40% of patients, strongly arguing that MDA-7/IL-24 could have significant therapeutic value. This review describes what is presently known about the impact of MDA-7/IL-24 on tumor cell biology and its potential therapeutic applications.

Original language	English (US)
Pages (from-to)	375-384
Number of pages	10
Journal	Pharmacology and Therapeutics
Volume	128
Issue number	2
DOIs	https://doi.org/10.1016/j.pharmthera.2010.08.001
State	Published - Nov 2010

Bibliographical note

Funding Information:
Support was provided by P01-CA104177 , R01-CA108325 , R01-DK52825 ; R01-CA063753 , R01-CA077141 , R01-CA097318 ; R01-CA127641 ; R01-CA098712 ; P01-NS031492 , the Samuel Waxman Cancer Research Foundation (SWCRF) and the National Foundation for Cancer Research (NFCR) . P.D. is the Universal Professor in Signal Transduction and P.B.F. holds the Thelma Newmeyer Corman Chair in Cancer Research and is a SWCRF Investigator.

Keywords

Apoptosis
Autophagy
Ca
Ceramide
Clinical trial
ER stress
IL-24
MCL-1
MDA-7
PERK
ROS
Signal transduction

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Dent, P., Yacoub, A., Hamed, H. A., Park, M. A., Dash, R., Bhutia, S. K., Sarkar, D., Wang, X. Y., Gupta, P., Emdad, L., Lebedeva, I. V., Sauane, M., Su, Z. Z., Rahmani, M., Broaddus, W. C., Young, H. F., Lesniak, M. S., Grant, S., Curiel, D. T., & Fisher, P. B. (2010). The development of MDA-7/IL-24 as a cancer therapeutic. Pharmacology and Therapeutics, 128(2), 375-384. https://doi.org/10.1016/j.pharmthera.2010.08.001

Dent, P, Yacoub, A, Hamed, HA, Park, MA, Dash, R, Bhutia, SK, Sarkar, D, Wang, XY, Gupta, P, Emdad, L, Lebedeva, IV, Sauane, M, Su, ZZ, Rahmani, M, Broaddus, WC, Young, HF, Lesniak, MS, Grant, S, Curiel, DT & Fisher, PB 2010, 'The development of MDA-7/IL-24 as a cancer therapeutic', Pharmacology and Therapeutics, vol. 128, no. 2, pp. 375-384. https://doi.org/10.1016/j.pharmthera.2010.08.001

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title = "The development of MDA-7/IL-24 as a cancer therapeutic",

abstract = "The cytokine melanoma differentiation associated gene 7 (mda-7) was identified by subtractive hybridization as a protein whose expression increased during the induction of terminal differentiation, and that was either not expressed or was present at low levels in tumor cells compared to non-transformed cells. Based on conserved structure, chromosomal location and cytokine-like properties, MDA-7, was classified as a member of the interleukin (IL)-10 gene family and designated as MDA-7/IL-24. Multiple studies have demonstrated that expression of MDA-7/IL-24 in a wide variety of tumor cell types, but not in corresponding equivalent non-transformed cells, causes their growth arrest and rapid cell death. In addition, MDA-7/IL-24 has been noted to radiosensitize tumor cells which in part is due to the generation of reactive oxygen species (ROS) and ceramide that cause endoplasmic reticulum stress and suppress protein translation. Phase I clinical trial data has shown that a recombinant adenovirus expressing MDA-7/IL-24 (Ad.mda-7 (INGN-241)) was safe and had measurable tumoricidal effects in over 40% of patients, strongly arguing that MDA-7/IL-24 could have significant therapeutic value. This review describes what is presently known about the impact of MDA-7/IL-24 on tumor cell biology and its potential therapeutic applications.",

keywords = "Apoptosis, Autophagy, Ca, Ceramide, Clinical trial, ER stress, IL-24, MCL-1, MDA-7, PERK, ROS, Signal transduction",

author = "Paul Dent and Adly Yacoub and Hamed, {Hossein A.} and Park, {Margaret A.} and Rupesh Dash and Bhutia, {Sujit K.} and Devanand Sarkar and Wang, {Xiang Yang} and Pankaj Gupta and Luni Emdad and Lebedeva, {Irina V.} and Moira Sauane and Su, {Zhao zhong} and Mohamed Rahmani and Broaddus, {William C.} and Young, {Harold F.} and Lesniak, {Maciej S.} and Steven Grant and Curiel, {David T.} and Fisher, {Paul B.}",

note = "Funding Information: Support was provided by P01-CA104177 , R01-CA108325 , R01-DK52825 ; R01-CA063753 , R01-CA077141 , R01-CA097318 ; R01-CA127641 ; R01-CA098712 ; P01-NS031492 , the Samuel Waxman Cancer Research Foundation (SWCRF) and the National Foundation for Cancer Research (NFCR) . P.D. is the Universal Professor in Signal Transduction and P.B.F. holds the Thelma Newmeyer Corman Chair in Cancer Research and is a SWCRF Investigator.",

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AU - Bhutia, Sujit K.

AU - Sarkar, Devanand

AU - Wang, Xiang Yang

AU - Gupta, Pankaj

AU - Emdad, Luni

AU - Lebedeva, Irina V.

AU - Sauane, Moira

AU - Su, Zhao zhong

AU - Rahmani, Mohamed

AU - Broaddus, William C.

AU - Young, Harold F.

AU - Lesniak, Maciej S.

AU - Grant, Steven

AU - Curiel, David T.

AU - Fisher, Paul B.

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N2 - The cytokine melanoma differentiation associated gene 7 (mda-7) was identified by subtractive hybridization as a protein whose expression increased during the induction of terminal differentiation, and that was either not expressed or was present at low levels in tumor cells compared to non-transformed cells. Based on conserved structure, chromosomal location and cytokine-like properties, MDA-7, was classified as a member of the interleukin (IL)-10 gene family and designated as MDA-7/IL-24. Multiple studies have demonstrated that expression of MDA-7/IL-24 in a wide variety of tumor cell types, but not in corresponding equivalent non-transformed cells, causes their growth arrest and rapid cell death. In addition, MDA-7/IL-24 has been noted to radiosensitize tumor cells which in part is due to the generation of reactive oxygen species (ROS) and ceramide that cause endoplasmic reticulum stress and suppress protein translation. Phase I clinical trial data has shown that a recombinant adenovirus expressing MDA-7/IL-24 (Ad.mda-7 (INGN-241)) was safe and had measurable tumoricidal effects in over 40% of patients, strongly arguing that MDA-7/IL-24 could have significant therapeutic value. This review describes what is presently known about the impact of MDA-7/IL-24 on tumor cell biology and its potential therapeutic applications.

AB - The cytokine melanoma differentiation associated gene 7 (mda-7) was identified by subtractive hybridization as a protein whose expression increased during the induction of terminal differentiation, and that was either not expressed or was present at low levels in tumor cells compared to non-transformed cells. Based on conserved structure, chromosomal location and cytokine-like properties, MDA-7, was classified as a member of the interleukin (IL)-10 gene family and designated as MDA-7/IL-24. Multiple studies have demonstrated that expression of MDA-7/IL-24 in a wide variety of tumor cell types, but not in corresponding equivalent non-transformed cells, causes their growth arrest and rapid cell death. In addition, MDA-7/IL-24 has been noted to radiosensitize tumor cells which in part is due to the generation of reactive oxygen species (ROS) and ceramide that cause endoplasmic reticulum stress and suppress protein translation. Phase I clinical trial data has shown that a recombinant adenovirus expressing MDA-7/IL-24 (Ad.mda-7 (INGN-241)) was safe and had measurable tumoricidal effects in over 40% of patients, strongly arguing that MDA-7/IL-24 could have significant therapeutic value. This review describes what is presently known about the impact of MDA-7/IL-24 on tumor cell biology and its potential therapeutic applications.

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The development of MDA-7/IL-24 as a cancer therapeutic

Abstract

Bibliographical note

Keywords

UN SDGs

Access

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