Study Explores Starving Malignant Cells to Boost I
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Posted On: 07/12/2024 4:47:20 PM
Study Explores Starving Malignant Cells to Boost Immunotherapy, Improve DNA Damage
Prostate cancer is challenging to treat, especially when the disease progresses to a castrate-resistant metastatic state. Conventional treatments, such as hormonal treatments, radiotherapy and chemotherapy, fail most times because of acquired resistance, off-target effects and toxicities.
It is well-known that amino acids perform important metabolic functions. While normal cells have lower demand for amino acids, cancer cells exhibit high demand for amino acids because of increased demand for cellular building blocks and energy.
Now a new study has determined that starving cancer cells may help improve immunotherapy response and increase damage to DNA, which in turn helps speed up death of cancer cells. The study was carried out by researchers Dawit Kidane and Aashirwad Shahi from Howard University.
In their study, the researchers looked into an alternative therapeutic approach that focuses on the metabolic vulnerabilities of prostate cancer cells. Metabolic reprograming is a distinctive feature of prostate cancer cells and is represented by tumor dependency on metabolic pathways to promote survival as well as growth.
In particular, the researchers focused on these cells’ reliance on amino acids such as cysteine. This nonessential amino acid is crucial in protein production, among other metabolic functions. The researchers hypothesized that targeting metabolism for cancer cells may improve response to therapy for treatment-resistant cancers while decreasing toxicities related to therapy.
For their study, the researchers used engineered enzyme cyst(e)inase to consume the cystine/cysteine and cause oxidative stress and damage to DNA in cancer cells. They observed that this depletion disturbed synthesis of glutathione, increased levels of reactive oxygen species and increased damage to cancer cell DNA, causing cell death.
The researchers also observed that DNA repair mechanisms protected cancer cells against DNA replication stress and reactive oxygen species-induced oxidative DNA damage.
In their report, the two explained how their data suggested that repair of lesions in DNA caused by reactive oxygen species needed the interaction of several repair pathways, including base excision repair. The researchers also discovered that the presence of both double- and single-strand DNA breaks in prostate cancer cells treated with cyst(e)inase, suggesting that other repair pathways could also play a role in protecting cells from this damage.
In addition, the researchers stated that the combined use of agents that targeted antioxidant defenses such as thioredoxins andcyst(e)inase further increased cytotoxicity and decreased tumor size in in-vivo models. This discovery highlights opportunities to increase the effectiveness of immune checkpoint inhibitors while improving tumor immunogenicity.
The researchers’ findings were reported in “Oncotarget.”
As more approaches to increase the efficacy of immunotherapies against cancer are developed, the immunotherapies brought to market by various companies such as Scinai Immunotherapies Ltd. (NASDAQ: SCNI) could help more people than the current limited pool of eligible patients.
NOTE TO INVESTORS: The latest news and updates relating to Scinai Immunotherapeutics Ltd. (NASDAQ: SCNI) are available in the company’s newsroom at https://ibn.fm/SCNI
Please see full terms of use and disclaimers on the BioMedWire website applicable to all content provided by BMW, wherever published or re-published: http://BMW.fm/Disclaimer
Prostate cancer is challenging to treat, especially when the disease progresses to a castrate-resistant metastatic state. Conventional treatments, such as hormonal treatments, radiotherapy and chemotherapy, fail most times because of acquired resistance, off-target effects and toxicities.
It is well-known that amino acids perform important metabolic functions. While normal cells have lower demand for amino acids, cancer cells exhibit high demand for amino acids because of increased demand for cellular building blocks and energy.
Now a new study has determined that starving cancer cells may help improve immunotherapy response and increase damage to DNA, which in turn helps speed up death of cancer cells. The study was carried out by researchers Dawit Kidane and Aashirwad Shahi from Howard University.
In their study, the researchers looked into an alternative therapeutic approach that focuses on the metabolic vulnerabilities of prostate cancer cells. Metabolic reprograming is a distinctive feature of prostate cancer cells and is represented by tumor dependency on metabolic pathways to promote survival as well as growth.
In particular, the researchers focused on these cells’ reliance on amino acids such as cysteine. This nonessential amino acid is crucial in protein production, among other metabolic functions. The researchers hypothesized that targeting metabolism for cancer cells may improve response to therapy for treatment-resistant cancers while decreasing toxicities related to therapy.
For their study, the researchers used engineered enzyme cyst(e)inase to consume the cystine/cysteine and cause oxidative stress and damage to DNA in cancer cells. They observed that this depletion disturbed synthesis of glutathione, increased levels of reactive oxygen species and increased damage to cancer cell DNA, causing cell death.
The researchers also observed that DNA repair mechanisms protected cancer cells against DNA replication stress and reactive oxygen species-induced oxidative DNA damage.
In their report, the two explained how their data suggested that repair of lesions in DNA caused by reactive oxygen species needed the interaction of several repair pathways, including base excision repair. The researchers also discovered that the presence of both double- and single-strand DNA breaks in prostate cancer cells treated with cyst(e)inase, suggesting that other repair pathways could also play a role in protecting cells from this damage.
In addition, the researchers stated that the combined use of agents that targeted antioxidant defenses such as thioredoxins andcyst(e)inase further increased cytotoxicity and decreased tumor size in in-vivo models. This discovery highlights opportunities to increase the effectiveness of immune checkpoint inhibitors while improving tumor immunogenicity.
The researchers’ findings were reported in “Oncotarget.”
As more approaches to increase the efficacy of immunotherapies against cancer are developed, the immunotherapies brought to market by various companies such as Scinai Immunotherapies Ltd. (NASDAQ: SCNI) could help more people than the current limited pool of eligible patients.
NOTE TO INVESTORS: The latest news and updates relating to Scinai Immunotherapeutics Ltd. (NASDAQ: SCNI) are available in the company’s newsroom at https://ibn.fm/SCNI
Please see full terms of use and disclaimers on the BioMedWire website applicable to all content provided by BMW, wherever published or re-published: http://BMW.fm/Disclaimer
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