ZyVersa Therapeutics Highlights Peer-Reviewed Article Linking Inflammasome Activation to Triple-Negative Breast Cancer Brain Metastasis
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The recent findings on the role of inflammasome activation, specifically the NLRP3 inflammasome, in the proliferation of triple negative breast cancer (TNBC) cells in the brain are significant. As an oncologist, I can confirm that TNBC is one of the most challenging breast cancer subtypes to treat due to its aggressive nature and lack of hormone receptors, which render hormonal therapies ineffective. The discovery that NLRP3 inflammasome activation leads to increased secretion of IL-1β, a pro-inflammatory cytokine and that this process is pivotal in brain metastasis provides a clear therapeutic target. The potential for inflammasome inhibitors like IC 100 to mitigate these effects could represent a substantial advancement in the management of TNBC with brain metastasis, a condition that severely limits treatment options and worsens prognosis.
Furthermore, the correlation of IL-1β expression with the size of metastatic lesions highlights a possible biomarker for disease progression. This could lead to more personalized treatment approaches, where the level of IL-1β expression informs the urgency and type of intervention. Given the high rate of brain metastasis in TNBC patients, the clinical implications of these findings are profound. The ability to inhibit a pathway that is central to the development of one of the most lethal aspects of this disease could improve survival rates and quality of life for affected patients.
The research on inflammasome inhibitors, specifically targeting NLRP3, opens up new avenues for the treatment of TNBC with brain metastasis. From a research perspective, the use of both in vivo and in vitro models, as well as human cultures, adds robustness to the study's findings. The data suggest that targeting the NLRP3 inflammasome could be effective in reducing the proliferation of TNBC cells in the brain, which is a significant breakthrough given the limited efficacy of current treatments for brain metastases.
It's also worth noting that the development of drugs like ZyVersa's IC 100 could have a ripple effect on the biopharmaceutical industry, potentially leading to increased investment in inflammasome research. The specificity of IC 100 in inhibiting up to 12 different inflammasomes may provide a wide therapeutic window, reducing off-target effects that are common with less selective anti-inflammatory drugs. This precision could lead to better patient outcomes and fewer side effects, which is a critical consideration in drug development. If clinical trials confirm the efficacy and safety of IC 100, it could set a precedent for the development of similar therapeutics targeting inflammasomes in various diseases.
From an investment perspective, the development of a novel therapeutic like IC 100 could have substantial implications for ZyVersa Therapeutics' market valuation. The publication of peer-reviewed research demonstrating the efficacy of their drug candidate in preventing the proliferation of TNBC cells in the brain could potentially lead to increased investor confidence. This is particularly relevant given the high unmet medical need for effective treatments for TNBC brain metastasis.
Moreover, the specificity of IC 100 in targeting multiple inflammasomes could position ZyVersa as a leader in this niche market. If subsequent clinical trials are successful, the company could secure a significant competitive advantage. Investors will be closely monitoring the progression of IC 100 through clinical trials, as positive results could lead to a surge in stock prices due to the anticipation of new revenue streams and market exclusivity. However, it is also crucial to consider the risks associated with drug development, including potential regulatory hurdles and the possibility of unsuccessful trial outcomes. Investors should maintain a balanced view of the potential risks and rewards associated with ZyVersa's pipeline.
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40% of women with triple negative breast cancer (TNBC) experience metastasis to their brain, which affects physical function, independence, personality, quality of life, and significantly increases mortality rates. - Published data demonstrate that inflammasome activation increases proliferation of TNBC cells in the brain, which was prevented by inhibition of NLRP3 inflammasomes in both mouse and human models.
- ZyVersa is developing Inflammasome ASC Inhibitor IC 100, which can inhibit up to 12 different inflammasomes (including NLRP3 inflammasomes) and their associated ASC specks which perpetuate damaging inflammation.
WESTON, Fla., Jan. 17, 2024 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA, or “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of inflammatory and renal diseases, announces publication of an article in the peer-reviewed journal, Acta Neuropathologica Communications, demonstrating that inflammasome activation enhances cancer metastasis to the brain in women with TNBC.
In the paper titled, “Inflammasome activation in peritumoral astrocytes is a key player in breast cancer brain metastasis development,” the authors evaluated in vivo and in vitro brain metastasis models, as well as human cultures of astrocytes and TNBC cells. Key findings are as follows:
- Activation of the NLRP3 inflammasome results in excretion of IL-1β in the tumor environment, enhancing proliferation of metastatic cells in the brain.
- Expression of IL-1β correlates with the size of metastatic lesions, being absent in tumor-free brain areas and more intense in the vicinity of large tumors in comparison to smaller ones.
- Inhibition of NLRP3 activation prevented proliferation of TNBC cells in both mouse and human models.
The authors stated, “We are the first to show that peritumoral reactive astrocytes promote the proliferation of TNBC cells in the brain through NLRP3 inflammasome-dependent secretion of IL-1β. Brain metastases are among the most aggressive and the least curable malignant tumors; therefore, we need novel therapies targeting mechanisms that contribute to the proliferation of metastatic cells in the brain.” They concluded, “We suggest that inflammasome inhibition might become a therapeutic option in this currently incurable disease.”
To read the article, click here.
“The research published in Acta Neuropathologica Communications linking inflammasome activation in patients with triple-negative breast cancer to brain metastasis supports a growing body of evidence about the role of dysregulated inflammasome pathways in a broad range of devastating diseases,” commented Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO, and President. “We are excited about the potential to transform the treatment of a multitude of inflammatory diseases with drugs like Inflammasome ASC Inhibitor IC 100. IC 100 uniquely inhibits inflammasome ASC and ASC specks to block initiation and perpetuation of damaging inflammation.” To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here.
About Inflammasome ASC Inhibitor IC 100
IC 100 is a novel humanized IgG4 monoclonal antibody that inhibits the inflammasome adaptor protein ASC. IC 100 was designed to attenuate both initiation and perpetuation of the inflammatory response. It does so by binding to a specific region of the ASC component of multiple types of inflammasomes, including NLRP1, NLRP2, NLRP3, NLRC4, AIM2, Pyrin. Intracellularly, IC 100 binds to ASC monomers, inhibiting inflammasome formation, thereby blocking activation of IL-1β early in the inflammatory cascade. IC 100 also binds to ASC in ASC Specks, both intracellularly and extracellularly, further blocking activation of IL-1β and the perpetuation of the inflammatory response that is pathogenic in inflammatory diseases. Because active cytokines amplify adaptive immunity through various mechanisms, IC 100, by attenuating cytokine activation, also attenuates the adaptive immune response.
About ZyVersa Therapeutics, Inc.
ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs for patients with renal and inflammatory diseases who have significant unmet medical needs. The Company is currently advancing a therapeutic development pipeline with multiple programs built around its two proprietary technologies – Cholesterol Efflux Mediator™ VAR 200 for treatment of kidney diseases, and Inflammasome ASC Inhibitor IC 100, targeting damaging inflammation associated with numerous CNS and other inflammatory diseases. For more information, please visit www.zyversa.com.
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