Princeton University researchers have been developing a new therapeutic agent to combat triple-negative breast cancer (TNBC), one of the most difficult to treat forms of malignancy. Their approach tackles two separate mechanisms for cancer’s growth and has shown some remarkable results so far.
Tinagl1 is based on a naturally occurring protein and manages to block two main pathways by which the mutated cells can grow and migrate out of the primary tumor to spread to other organs in the body. “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”, noted Professor of Molecular Biology Yibin Kang.
Tubulointerstitial Nephritis Antigen-like 1 inhibits both a tumor-promoting protein known as epidermal growth factor receptor gene (EGFR) and certain molecules, called integrins, which are involved in regulating cellular migration to new locations, adhesion to other cells, and transformation into tumors.
In general, patients with TNBC are prone to recurrence and have limited treatment options. The disease gets its name from the lack of three prominent biological targets – the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2). Estimates say it accounts for 10 to 20 percent of all breast cancer cases.
The team looked at over 800 samples and noticed that lower expressions of the Tinagl1 gene were more likely to have come from patients with advanced tumor stages and shorter survival times. Laboratory-engineered tumor models with boosted levels of Tinagl1 produced slower-growing tumors that were less likely to metastasize to the lung.
Animal testing confirmed their theory as mice with mammary tumors that had doses of this protein administered showed significantly inhibited primary tumor growth and spontaneous lung metastasis while having no significant side effects.
Even though the compound has proven its effectiveness, there are still many details to address before human trials can begin. Nevertheless, the team is hoping to eventually create an improved treatment in the near future.
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