Considerations in Optimizing Radiation Therapy for Non-small Cell Lung Cancer

Greenberger, Joel S.; Bahri, Sanjeev; Jett, James R.; Belani, Chandra P.; Kalend, A.M.; Epperly, Michael W.

doi:10.1378/chest.113.1_supplement.46s

Cited by 9 publications

(5 citation statements)

References 26 publications

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“…As delivery of new inhalation gene therapy vectors becomes feasible, 25 use of radioprotective gene therapy programs in fractionated radiotherapy of thoracic tumor volumes or in total body irradiation patients 3 may become practical for reducing side-effects, including those mediated by lung tissue radiation damage. [26][27][28][29] Gene Therapy…”

Section: Discussionmentioning

confidence: 99%

Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation

et al. 2000

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To determine whether intratracheal (IT) lung protective manganese superoxide-plasmid/liposomes (MnSOD-PL) complex provided 'bystander' protection of thoracic tumors, mice with orthotopic Lewis lung carcinoma-bacterial ␤-galactosidase gene (3LL-LacZ) were studied. There was no significant difference in irradiation survival of 3LL-LacZ cells irradiated, then cocultured with MnSOD-PL-treated compared with control lung cells (D 0 2.022 and 2.153, respectively), or when irradiation was delivered 24 h after coculture (D 0 0.934 and 0.907, respectively). Tumor-bearing control mice showed 50% survival at 18 days and 10% survival at 21 days. Mice receiving liposomes with no insert or LacZ-PL complex plus 18 Gy had 50% survival at 22 days,

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Section: Discussionmentioning

confidence: 99%

Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation

et al. 2000

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“…Because the first encouraging experimental and clinical trials with liposomal SOD reduced chronic skin fibrosis following irradiation 3, viral approaches were considered to attempt to improve the level of SOD in tissues. The adenovirus mediated SOD gene therapy reduced fatal pneumonitis in mice with radiation‐induced pneumonitis 7; however, the viral toxicity precluded further studies and translation to human use 9. Another promising approach has been to use a synthetic SOD mimetics with and without catalase 21, 22.…”

Section: Discussionmentioning

confidence: 99%

“…Different formulations of SOD and synthetic SOD mimetics used in preclinical models also show promise 5–8. More recently, adenovirus‐mediated SOD gene transfer demonstrated efficient expression of SOD, but provoked a strong innate immune response in mice 7, 9.…”

Section: Introductionmentioning

confidence: 99%

Mitigation of radiation‐induced skin injury by AAV2‐mediated MnSOD gene therapy

Yan

Brown

Kolozsvary

et al. 2008

The Journal of Gene Medicine

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“…More recently, attempts to improve the therapeutic ratio, three‐dimensional conformal radiation therapy has been combined with gene therapy for radiation protection using an inhaled manganese‐superoxide‐dismutase (MnSOD) transgene [Greenberger et al, 1998]. Animal studies, in which mice with orthotopic lung carcinoma tumors received intratracheal transfer of MnSOD‐plasmid/liposomes (MnSOD‐PL) followed by irradiation, showed improved survival [Epperly et al, 2000].…”

Section: Overcoming Limitations Of Gene Therapymentioning

confidence: 99%

Gene therapy for lung cancer

Toloza

Morse

Lyerly

2006

J of Cellular Biochemistry

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Lung cancer patients suffer a 15% overall survival despite advances in chemotherapy, radiation therapy, and surgery. This unacceptably low survival rate is due to the usual finding of advanced disease at diagnosis. However, multimodality strategies using conventional therapies only minimally improve survival rates even in early stages of lung cancer. Attempts to improve survival in advanced disease using various combinations of platinum-based chemotherapy have demonstrated that no regimen is superior, suggesting a therapeutic plateau and the need for novel, more specific, and less toxic therapeutic strategies. Over the past three decades, the genetic etiology of cancer has been gradually delineated, albeit not yet completely. Understanding the molecular events that occur during the multistep process of bronchogenic carcinogenesis may make these tasks more surmountable. During these same three decades, techniques have been developed which allow transfer of functional genes into mammalian cells. For example, blockade of activated tumor-promoting oncogenes or replacement of inactivated tumor-suppressing or apoptosis-promoting genes can be achieved by gene therapy. This article will discuss the therapeutic implications of these molecular changes associated with bronchogenic carcinomas and will then review the status of gene therapies for treatment of lung cancer.

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Considerations in Optimizing Radiation Therapy for Non-small Cell Lung Cancer

Cited by 9 publications

References 26 publications

Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation

Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation

Mitigation of radiation‐induced skin injury by AAV2‐mediated MnSOD gene therapy

Gene therapy for lung cancer

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