On August 29, 2023 Shuttle Pharmaceuticals Holdings, Inc. (Nasdaq: SHPH), a discovery and development stage specialty pharmaceutical company focused on improving the outcomes of cancer patients treated with radiation therapy (RT), reported the publication of a manuscript reporting on the ability of Shuttle’s lead Histone deacetylase 6 (HDAC6) inhibitor drug candidate (SP-2-225) to stimulate the innate immune system following radiation therapy (Press release, Shuttle Pharmaceuticals, AUG 29, 2023, View Source [SID1234634761]). The manuscript, titled "Radiation therapy-induced immune response enhanced by selective HDAC6 Inhibition," was reported by first author Dr. Satish Noonepalle, Assistant Professor at Georgetown University and the Lombardi Comprehensive Cancer Center, and published in Molecular Cancer Therapeutics, a scientific journal affiliated with the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the premier international cancer research society.
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"The report highlights to the scientific and financial community how our novel selective inhibitor (SP-2-225) is able to target the HDAC6 function in tumors to inhibit tumor growth and enhance the M1/M2 ratio of infiltrating macrophages within tumors as a combination therapy with RT," commented Anatoly Dritschilo, M.D., CEO of Shuttle Pharmaceuticals and a co-author of the report. "These observations support a strategy to advance the use of selective HDAC6 inhibitors to improve antitumor immune responses and prevent tumor relapse post-radiation therapy."
RT is a curative cancer treatment modality that imparts damage to cellular DNA, induces immunogenic cell death, and activates antitumor immunity. Despite the RT-induced direct antitumor effect seen within the treated volume, accumulating evidence indicates activation of innate antitumor immunity. Acute proinflammatory responses mediated by anticancer M1 macrophages are observed in the immediate aftermath following RT. However, after a few days, these M1 macrophages are converted to anti-inflammatory and pro-cancer M2 phenotype, leading to cancer resistance and underlying potential tumor relapse.
The study was supported by NIH grant R01CA249248, and Cancer Research Institute Grant #228514 to Dr. Alejandro Villagra, and HDAC6 inhibitor SP-2-225 was provided at no charge by Shuttle Pharmaceuticals, Inc. under a material transfer agreement.
A copy of the publication is available at: View Source
Molecular Cancer Therapeutics publishes translational research studies focused on the discovery and preclinical development of therapeutic agents for oncology. To reflect the evolving field of therapeutics, the journal’s interest extends to all selective drugs including small molecule inhibitors, antibody-drug conjugates, antibody cytokine fusions, bispecific antibodies, cell therapies, gene therapies, radio-immunotherapeutics, vaccines, viral therapies, and other experimental approaches in oncology.