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The role of TRK receptors in our body

Tropomyosin receptor kinase or “TRK” receptors are one of the most fundamental receptors in the human body. These receptors are crucial for the cellular growth and development of a properly functioning nervous system and play a critical role in neuronal signaling throughout our bodies. Nearly 75 years of scientific research has shown that dysregulation of TRK receptors plays a key role in a variety of disorders. By selectively and precisely controlling the actions of TRK receptors, we can regulate the symptoms and alter the progression of diseases.

TRK inhibitor therapies can play a vital role

For years, pharmaceutical researchers have focused on TRK receptors in developing new treatments for pain, oncology, neuroscience, ophthalmology, rheumatology and dermatology. Recent clinical trials have demonstrated promising results in a number of these research programs. Despite these advances, there are still millions of patients worldwide living with diseases and conditions where TRK modulator therapies could play a vital role, and for whom there are presently no viable treatment options.

The Role of TRK Receptors in Oncology

The TRK family is comprised of four different cell surface receptors: TRKA, TRKB, TRKC and P75. Three of these subtypes, TRKA, TRKB and TRKC, share structural elements which provide a common target for regulation. These three TRK receptors are encoded by three unique genes called NTRK1, NTRK2 and NTRK3, respectively. In healthy individuals, TRK receptors are typically found in nerve cells, and are activated when they bind with specific extracellular proteins called neurotrophins. When neurotrophins bind to TRK receptors, they activate the signaling pathways inside the cell that help regulate how our neurons function, establishing how we feel pain, how we move, our cognitive abilities, and many other key roles throughout the body.

When an NTRK gene abnormally combines with another gene, a resulting hybrid known as a TRK gene fusion can emerge. These gene fusions exist in a continuously activated form, no longer requiring the binding of neurotrophins to initiate the signaling pathways. Consequently, these gene fusions lead to uncontrolled cellular growth, tumor proliferation and cancer. TRK gene fusions have already been identified in over 40 different types of cancers throughout the human body and can be diagnosed by several genetic profiling technologies. Patients with TRK gene fusions are often particularly sensitive to TRK inhibitor treatments and have shown remarkable clinical benefits in some cases.

The Role of TRK Receptors in Dermatology

Overactivation of TRK receptors is a key driver in several inflammatory skin disorders, including psoriasis and atopic dermatitis. Hyperactivity of the TRK signaling pathway can result in a multitude of physical manifestations which are commonly associated with these dermatological diseases, such as pruritus or itch sensation, pain, inflammation and the development of lesions or plaques on the skin. By using a targeted approach to selectively reduce the TRK activity in the skin, patients with certain inflammatory skin diseases can be alleviated of many of their most debilitating symptoms.

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