Radiation Biomarkers: Can Small Businesses Drive Accurate Radiation Precision Medicine?

Abstract:

:Radiation therapy is an essential component of cancer treatment. Currently, tumor control and normal tissue complication probabilities derived from a general patient population guide radiation treatment. Its outcome could be improved if radiation biomarkers could be incorporated into approaches to treatment. A substantial number of cancer patients suffer from side effects of radiation therapy. These side effects can result in treatment interruption. Such unplanned treatment interruptions not only jeopardize anticancer treatment efficacy but also result in poor post-treatment quality-of-life. To develop and translate radiation biomarkers for clinical use, NCI's Radiation Research Program, in collaboration with the Small Business Innovation Research Development Center, funded four small businesses through the request for proposals after peer review during 2015-2019. Here, we summarize publicly available information on intellectual property rights, the status of development, ongoing clinical trials, success in obtaining financing and regulatory approval. An analysis of publicly available information indicates all four companies have completed phase I of SBIR funding and advanced to further development, validation and clinical trials with phase II SBIR funding. These biomarkers are: 1. A panel of genomic biomarkers of radiation response to predict toxicity and radioimmune response (MiraDx Inc., Los Angeles, CA); 2. A multiplex assay for single nucleotide polymorphism (SNP) biomarkers of radiation sensitivity to identify a subset of prostate cancer patients for which radiotherapy is contraindicated (L2 Diagnostics, New Haven, CT); 3. A cell-free DNA assay in blood to measure tissue damage shortly after radiation exposure (DiaCarta Inc., Richmond, CA); and 4. A metabolomic/lipidomic assay to predict late effects that adversely affect quality-of-life among patients treated with radiation for prostate cancer (Shuttle Pharmaceuticals, Rockville, MD). This work also provides a bird's eye view of the process of developing radiation biomarkers for use in radiation oncology clinics, some of the challenges and future directions.

journal_name

Radiat Res

journal_title

Radiation research

authors

Prasanna PGS,Narayanan D,Zhang K,Rahbar A,Coleman CN,Vikram B

doi

10.1667/RR15553.1

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

199-208

issue

3

eissn

0033-7587

issn

1938-5404

pii

10.1667/RR15553.1

journal_volume

193

pub_type

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  • Biological responses in known bystander cells relative to known microbeam-irradiated cells.

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    doi:10.1667/0033-7587(2002)158[0023:aopsib]2.0.co;2

    authors: Abdoul-Carime H,Cecchini S,Sanche L

    更新日期:2002-07-01 00:00:00

  • Acute effects of whole-body proton irradiation on the immune system of the mouse.

    abstract::The acute effects of proton whole-body irradiation on the distribution and function of leukocyte populations in the spleen and blood were examined and compared to the effects of photons derived from a (60)Co gamma-ray source. Adult female C57BL/6 mice were exposed to a single dose (3 Gy at 0.4 Gy/min) of protons at sp...

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    authors: Kajioka EH,Andres ML,Li J,Mao XW,Moyers MF,Nelson GA,Slater JM,Gridley DS

    更新日期:2000-05-01 00:00:00

  • Serum copper concentration as an index of lung injury in rats exposed to hemithorax irradiation.

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    pub_type: 杂志文章

    doi:

    authors: Ward WF,Molteni A,Fitzsimons EJ,Hinz J

    更新日期:1988-06-01 00:00:00

  • Microcollimator for micrometer-wide stripe irradiation of cells using 20-30 keV X rays.

    abstract::Abstract Pataky, K., Villanueva, G., Liani, A., Zgheib, O., Jenkins, N., Halazonetis, D. J., Halazonetis, T. D. and Brugger, J. Microcollimator for Micrometer-Wide Stripe Irradiation of Cells Using 20-30 keV X Rays. Radiat. Res. 172, 252-259 (2009). The exposure of subnuclear compartments of cells to ionizing radiatio...

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    doi:10.1667/RR1483.1

    authors: Pataky K,Villanueva G,Liani A,Zgheib O,Jenkins N,Halazonetis DJ,Halazonetis TD,Brugger J

    更新日期:2009-08-01 00:00:00

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    journal_title:Radiation research

    pub_type: 杂志文章

    doi:

    authors: Banerjee S,Bhaumik G,Bhattacharjee SB

    更新日期:1989-08-01 00:00:00

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    abstract::A study has been made of methods for rapidly inactivating cells of E. coli at neutral pH to prevent enzymatic, chemical, or physical modification to DNA damaged by irradiation. The radiation was delivered in a fraction of a second using an electron accelerator. Cell inactivation was with ethanol or a solution (CSE) co...

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    pub_type: 杂志文章

    doi:

    authors: Tilby MJ,Loverock PS

    更新日期:1983-11-01 00:00:00

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    abstract::The effect of exposure of human epidermal keratinocytes to ionizing radiation, both in vivo and in vitro, on the expression of the epidermal growth factor receptor (EGF-R) was studied on the protein, mRNA, and functional levels. Quantitative fluorometry of short-term organ cultures incubated with a monoclonal antibody...

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    pub_type: 杂志文章

    doi:

    authors: Peter RU,Beetz A,Ried C,Michel G,van Beuningen D,Ruzicka T

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    doi:

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    doi:

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    doi:

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    doi:

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    doi:

    authors: Dubois A,Fiala N,Boward CA,Bogo V

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    pub_type: 杂志文章

    doi:

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  • Neoplastic transformation of C3H/10T1/2 cells following exposure to 120-Hz modulated 2.45-GHz microwaves and phorbol ester tumor promoter.

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    doi:

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    doi:

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    doi:

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    doi:

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    doi:

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    doi:

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