Statistics predict that 44% of men and 38% of women will develop cancer at some point during their lifetime. Cancer occurs when abnormal cells grow uncontrollably, destroying the surrounding body tissue. Triple Negative Breast Cancer (TNBC) is a type of cancer that produces tumors that lack the expression of the hormonal receptors that are found some treatable forms of cancer. Of all types of cancers, TNBC is associated with the worst prognosis and accounts for approximately 20% of all cancer cases (Fisk 2019). There is a great need for a TNBC treatment and centrosomal regulators may be the solution. Centrosomes are specialized structures near the nucleus of the cell that serve a crucial role in cellular division and in maintaining the stability of the cell’s genetic information, but when centrosomes are defective, they can drive genetic instability in human breast and prostate cancers. In a normal cell, the centrosome is controlled by a set of regulatory proteins that ensure that it segregates only once during the synthesis (S) phase of the cellular division process. Alterations in the gap-1 (G1) and S phase regulating proteins are frequently observed in human cancer cells (Krämer et al. 2002). The first protein found to be associated with this defect in centrosome duplication is Mps1, a protein kinase that is required for centrosome duplication. In cancer cells, an increase in the activity of Mps1 was observed during the transition between G1 and S phase when there was very little of the protein
present (see Figure 2), suggesting that there was a defect in the regulation of this protein. Therefore, an Mps1 inhibitor should retard tumor growth by preventing the protein from producing the extra centrosomes that drive genetic instability. This idea was supported by a computationally designed Mps1 inhibitor that demonstrated the ability to reduce tumor growth without poisoning the body. This suggests that Mps1 is a candidate for targeted TNBC therapy (Fisk 2019).Figure 2: (Fisk 2019)
I found the process of drug development to be the most interesting component of this seminar. After determining that Mps1 was linked to the production of excess centrosomes, Fisk identified a lead compound that could inhibit its function. This was just the first step of the process. He stated that after identifying this compound, he had to work alongside a chemist to adjust its structure by manipulating the carbons. This is done with the goal of creating a new compound that will hopefully only bind to the target protein and that will not poison the body. This process can begin with anywhere between 5,000 and 10,000 different compounds and only results in only one FDA-approved drug. Through the use of computer technology, Fisk was able to see that “Compound 13” was able to decrease tumor growth when compared to a control without any toxicity (poisoning to the body) (Fisk 2019).
The first major takeaway from the seminar is that there is a great need for TNBC treatments....