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Naturally Occurring Protein Controls Growth and Spread of Triple Negative Breast Cancer
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Naturally Occurring Protein Controls Growth and Spread of Triple Negative Breast Cancer

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Highlights:
  • Triple negative breast cancer is a particularly serious form of breast cancer with limited treatment options, and associated with high rates of recurrence and an overall unfavorable patient prognosis
  • Tinagl1 protein, an experimental agent based on a naturally occurring protein shown to be effective in preventing growth and spread of cancer cells in triple negative breast cancer by inhibiting two important pathways that make this cancer highly aggressive
  • The two major pathways attacked by Tinagl1 protein include the epidermal growth factor receptor (EGFR) and integrin signaling pathways

There is some good news for patients who suffer from the aggressive form of 'Triple negative breast cancer.' This is a type of breast cancer that is known to have high rates of recurrence rate and an overall poor prognosis. Tinagl1 protein in a recent study conducted at Princeton University, has been found to be effective in controlling the growth and spread of cancer cells of these triple negative breast cancer.

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The findings of the study appear in the journal Cancer Cell.

Testing Efficacy of Tinagl1 Therapy in Controlling Tumor Growth

  • The study team genetically engineered human and mouse tumor cells to express high levels of the Tinagl1 protein.
  • They found that high levels of expression of Tinagl1 in mouse cancer cells made them grow slowly and less likely to spread to other sites
  • The team also administered Tinagl1 protein to mice with breast tumors and found that within seven weeks, there was significant reduction in the growth of the primary tumor and spread to lungs with no major adverse effects
  • Tinagl1 protein was found to effectively block both EGFR and integrin/FAK signaling pathways, resulting in better control of tumor growth and spread compared to single agent inhibitors
The findings of the study suggest that Tinagl1 protein is able to simultaneously block the two key pathways in triple negative breast cancer, thereby destroying the tumor cells and less likely to escape or find ways to compensate.

"People have tried to block the spread of this form of cancer but attempts so far have failed because if you try one approach, the cancer cells compensate by finding a way to escape," said Yibin Kang, the Warner-Lambert/Parke-Davis Professor of Molecular Biology at Princeton University, associate director for consortium research at the Rutgers Cancer Institute of New Jersey, and senior author on the study.

Timing of Tinagl1 Treatment

The team found that Tinagl1 protein was also effective in preventing further growth and spread of tumors that had already started to metastasize.
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Tinagl1 Protein - Inhibiting Two Major Pathways in Triple Negative Breast Cancer
  • Triple negative breast cancer is particularly aggressive and hard to treat due to the activity of the two pathways namely epidermal growth factor receptor (EGFR) and integrin signaling pathways
  • Until now treatments have focused on suppressing either one of the pathways, but the tumor cells manage to evade treatment and find a way to escape by finding alternate pathways
  • Tinagl1 protein suppressed the two major pathways simultaneously in a distinct manner leaving the tumor cells little room for escape or compensate, much like killing two birds with one stone
  • Tinagl1 protein was found to suppress the activity of the mutated EGFR protein, and simultaneously inhibits the integrin/FAK signaling pathways, both of which promote the uncontrolled growth and survival of tumor cells and spread of tumor cells to other parts of the body

Tinagl1 Expression in Human Breast Cancers

The study team analyzed over 800 tumor samples obtained from breast cancer patients
  • Patients with advanced stage of cancer at diagnosis and shorter duration of survival had decreased expression of Tinagl1 protein
  • Patients with high levels of expression of Tinagl1 protein had better survival and prognosis
  • The difference in patient outcome was most marked in the subset of patients with triple negative breast cancer

Triple Negative Breast Cancer in Brief

Triple negative breast cancer is a fast growing and aggressive form of breast cancer accounting for more than 15% of all breast cancer cases. It gets its name from the fact that this form of breast cancer lacks all the three major biological targets of breast cancer therapy namely estrogen receptor (ER), progesterone receptor (PR) and and the human epidermal growth factor receptor 2 (HER2), making the tumor very difficult to treat with high recurrence rates and poor patient outcome.

Summary - The findings of the current study suggest that recombinant Tinagl1 protein could find application in the treatment of triple negative breast cancer, warranting further research.

Reference :
  1. Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling - (http://dx.doi.org/10.1016/j.ccell.2018.11.016)


Source: Medindia

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