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Clinical Implications and Impact of Discovery of the Thyroid Hormone Receptor on Integrin αvβ3 (T3 therapy may be safer than T4 for cancer patients)

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  • Clinical Implications and Impact of Discovery of the Thyroid Hormone Receptor on Integrin αvβ3 (T3 therapy may be safer than T4 for cancer patients)

    Hypothyroidism has been reported to improve survival in cancer patients but only recently has the putative mechanism been identified as a receptor for thyrox...


    Front. Endocrinol., 23 August 2019 | https://doi.org/10.3389/fendo.2019.00565
    Clinical Implications and Impact of Discovery of the Thyroid Hormone Receptor on Integrin αvβ3–A Review
    Aleck Hercbergs*
    • Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, United States
    T4 and Cancer Biology

    T4 in physiological free hormone concentrations stimulates proliferation of cancer cells in vitro and in xenografts (13, 3945). Preclinical studies of tetrac, which blocks thyroid hormone action at integrin αvβ3, have shown arrested tumor growth (7, 11) in a variety of tumor xenografts including xenografts of renal cell carcinoma (13), non-small cell lung carcinoma (46), medullary carcinoma of the thyroid (41), pancreatic carcinoma (43), and multi-drug resistant breast cancer (47).
    Euthyroid Hypothyroxinemia and Divergence of Action Between T4 and T3

    This is a eumetabolic state maintained in the total absence of blood thyroxine by providing exogenous T3. The individual can therefore live and perform all normal daily activities and functions as prior to removal of the source of T4 or post total thyroidectomy. Preclinical evidence (12) indicates that T3, bound with a lower affinity by αvβ3 (9), is of low activity at physiological levels at the receptor (5, 39). The clinical ramifications of these effects on cancer cells are supported by the results of induction of the state of euthyroid hypothyroxinemia in patients with advanced cancers and with normal thyroid function (1).

    In a compassionate-need study of terminal patients with a variety of incurable solid tumors, extended survival was observed in a majority of patients using exogenous T3 to induce and maintain hypothyroxinemia. T3 administration prevented symptomatic hypothyroidism. Low odds of survival were surmounted in 19 of 23 patients (83%) who exceeded the expected median survival of literature-reported series used as controls (1). An additional approach is to terminate exogenous T4 supplementation to allow the T4 level to decline and supplement with T3 titrated individually to the patient's functional needs. Examples of the outcomes of this strategy on advanced disease (glioblastoma and sarcoma) are shown in Figures 35.
    Conclusion
    Identification of the integrin αvβ3 receptor pathway promises a paradigm changing approach to manage and treat cancer more effectively than currently available modalities.
    _____________________________________________

    Ask Congress to Investigate COVID Origins and Government Response to Pandemic.

    i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

    "...there’s an obvious contest that’s happening between different sectors of the colonial ruling class in this country. And they would, if they could, lump us into their beef, their struggle." ---- Omali Yeshitela, African People’s Socialist Party

    (My posts are not intended as advice or professional assessments of any kind.)
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  • #2


    Wu, C?C, Islam, MM, Nguyen, PA, et al. Risk of cancer in long?term levothyroxine users: Retrospective population?based study. Cancer Sci. 2021; 00: 1? 9. https://doi.org/10.1111/cas.14908

    Abstract

    Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. The relationship between levothyroxine use and cancer risk is largely underdetermined. To investigate the magnitude of the possible association between levothyroxine use and cancer risk, this retrospective case?control study was conducted using Taiwan?s Health and Welfare Data Science Center database. Cases were defined as all patients who were aged ?20 years and had a first?time diagnosis for cancer at any site for the period between 2001 and 2011. Multivariable conditional logistic regression models were used to calculate an adjusted odds ratio (AOR) to reduce potential confounding factors. A total of 601 733 cases and 2 406 932 controls were included in the current study. Levothyroxine users showed a 50% higher risk of cancer at any site (AOR: 1.50, 95% CI: 1.46?1.54; P < .0001) compared with non?users. Significant increased risks were also observed for brain cancer (AOR: 1.90, 95% CI: 1.48?2.44; P < .0001), skin cancer (AOR: 1.42, 95% CI: 1.17?1.72; P < .0001), pancreatic cancer (AOR: 1.27, 95% CI: 1.01?1.60; P = .03), and female breast cancer (AOR: 1.24, 95% CI: 1.15?1.33; P < .0001). Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Levothyroxine remains a highly effective therapy for hypothyroidism; therefore, physicians should carefully consider levothyroxine therapy and monitor patients? condition to avoid negative outcomes. Additional studies are needed to confirm these findings and to evaluate the potential biological mechanisms.
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    Full text at link. Below a patient advocate shares his thoughts.

    I would like to urge any reader to read the entire article and the content of the links prior to considering the implications. The research I am referring to will not apply to everyone on Levothyroxine. Many thyroid patients will do just fine on Levo and never have any issues. So, it is important to…
    _____________________________________________

    Ask Congress to Investigate COVID Origins and Government Response to Pandemic.

    i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

    "...there’s an obvious contest that’s happening between different sectors of the colonial ruling class in this country. And they would, if they could, lump us into their beef, their struggle." ---- Omali Yeshitela, African People’s Socialist Party

    (My posts are not intended as advice or professional assessments of any kind.)
    Never forget Excalibur.

    Comment


    • #3
      For many decades, scientists have been studying the effect of thyroid hormones in promoting cancer proliferation. Confusion and contradictions often arise in “cancer & thyroid” rese…

      Cancer scientists point finger at T4 & RT3 hormones

      By thyroidpatientsca on February 5, 2020
      _____________________________________________

      Ask Congress to Investigate COVID Origins and Government Response to Pandemic.

      i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

      "...there’s an obvious contest that’s happening between different sectors of the colonial ruling class in this country. And they would, if they could, lump us into their beef, their struggle." ---- Omali Yeshitela, African People’s Socialist Party

      (My posts are not intended as advice or professional assessments of any kind.)
      Never forget Excalibur.

      Comment


      • #4
        bump this

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