A study is being done by Dr Barani and her team, under the expert guidance of Prof Dr Srikumar Chakravarthi, affiliated to MAHSA University, to assess the levels of nectin-4 protein expression by triple negative breast cancer. It is expected that if nectin-4 protein is found to be expressed in high levels in triple negative breast cancers (just like other solid tumours such as bladder cancer), it will serve as an opportunity to make anti-nectin4 drug as a treatment option for patients fighting this challenging and difficult to treat cancer.
Triple-negative breast cancer is defined by its lack of expression of estrogen receptor, progesterone receptor, and HER2/neu protein. By preventing either the body's ability to manufacture hormones or the impact that hormones have on breast cancer cells, hormone treatment (anti-estrogen) slows or prevents the growth of hormone-sensitive tumours. Hormone treatment is ineffective on tumours that are hormone insensitive because they lack hormone receptors.
The growth-promoting protein known as HER2 is overproduced by the cancer cells in about 15–20% of breast malignancies. These malignancies, referred to as HER2-positive breast cancers, have a propensity for faster growth and metastasis than HER2-negative breast cancers. The HER2 protein has been the target of several therapeutic developments. Monoclonal antibodies are modified immune system proteins (antibodies) created by humans that have been programmed to bind to a particular target. In this instance, they bind to the HER2 protein on breast cancer cells, which can aid in inhibiting the growth of the cancer cells. Anti-HER2 treatments have significantly increased both early-stage and advanced-stage patient survival since they were first used to treat HER2-positive breast cancer patients. Cancers that are HER2 negative do not respond to anti-HER2 therapies.
Tumours that lack both hormone receptors and lack HER2 proteins are called as triple negative breast cancers. It is recognised as a clinicopathologic entity that exhibits aggressive behaviour and has a bad prognosis. The best course of treatment is still uncertain, and standard therapy is linked to high rates of recurrence. When compared to other breast cancer subtypes, triple negative breast cancers have a worse prognosis, a shorter disease-free survival rate, and a higher propensity for distant metastases. It is crucial that we identify the molecular characteristics of this breast cancer subgroup and identify precise indicators that may be applied in the identification and treatment option for this disease.
Many malignant cancers have been reported to over-express the Nectin cell adhesion protein 4 (Nectin-4). Such abnormal high expression is linked to the development of cancer and a bad prognosis. Nectin-4 has recently emerged a s a possible cancer biomarker and prospective target for treatment. Preclinical models consistently showed that Nectin-4 was located in the membrane and cytoplasm of cancer cells. Furthermore, Nectin-4 was overexpressed regardless of where the solid tumours were located. Interesting research has shown that bladder urothelial cancer exhibits heterogeneous Nectin-4 expression. A high blood level of nectin-4 was associated with disease progress and therapy effectiveness. Eventually, Nectin-4-targeting anti-drug conjugates caused cell death in a variety of tumour cell types. Because of its crucial involvement in carcinogenesis and lymphangiogenesis, nectin-4 appears to be a suitable target for the development of anticancer therapies. Enfortumab vedotin, which targets Nectin-4, showed positive outcomes and should be pursued.
The adhesion molecule nectin-4 represents a novel potential therapeutic target in breast cancer models. Researchers all over the world are testing the prognostic value of nectin-4 expression and assessed the therapeutic efficiency of an anti-nectin 4 antibody drug conjugate (ADC) on localised and metastatic TNBC in vitro and in vivo. Dr Barani and her research team from Mahsa University are currently testing the Nectin-4 expression levels in triple negative breast cancers by means of immunohistochemistry. This is a preliminary tissue based experiment which is being funded by Mahsa University internal research grant. The results of this research will contribute to the existing knowledge on Nectin-4 expression levels in triple negative breast cancers and pave the way forward for anti-nectin4 target therapy to be recognised as a novel and effective treatment option for patients fighting triple negative breast cancer.
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https://doi.org/10.1158/1535-7163.MCT-21-0846