Breast cancer is the second most common and third deadliest malignancy throughout the world. Although advanced diagnostics, early screening, and improved therapeutics have decreased the total morbidity and mortality associated with a variety of breast cancers, little is known about the therapeutic management of triple-negative breast cancer (TNBC).
Researchers and investigators at the University of Houston (UH) are studying the patho-physiological characteristics of TNBC in order to develop functional therapies for the management and treatment in patients.
Triple-negative breast cancers (TNBC) are considered to be the most aggressive variety of breast cancers due to their BRCA association, high metastatic potential, aggressive course, poor prognosis and occurrence in young females. As a rule, almost 12% of the entire female population is at risk of developing malignancy of breast tissue at some point of their life. Inheritance of certain genetic mutations like BRCA1 can increase the risk even further (up to 55- 65%). Likewise, 45% of the female population who inherit BRCA2 may develop breast cancer during entire lifetime. According to estimates, approximately 5 to 10% of all breast cancers have a BRCA association (that is more established in TNBC cancer type).
Details of the study:
Previous research suggested that the MELK (or Maternal Embryonic Leucine-Zipper Kinase) protein may play a possible role in breast cancer pathogenesis. The team at University of Houston conducted extensive experimentation to observe the effect of MELK inactivation on TNBC cells and reached a few key conclusions.
Marisa Simon, an undergraduate research fellow and biology senior, explained the findings:
“It’s been shown that MELK is in its highest concentrations during cell division. My hypothesis is that MELK safeguards cellular division by blocking the possibility of cell death. This blocking of cell death also can contribute to the longevity of cells. This gives researchers a potential target for cancer therapy. If MELK is essential to the division of cancer cells, then inhibiting it could inhibit and decrease tumor formation. Knowing what is affected by inactivating MELK will help researchers identify not only whether inhibiting it is effective, but also if it is safe.”
Simon also collaborated with Fehmi Masmar and assistant professor of Nuclear Receptors and Cell Signaling (CNRCS) at UH, Cecilia Williams, in discovering several other proteins that may also contribute to the development of TNBC in addition to MELK. Further research and investigation is underway to diagnose the pathogenic mechanisms and interactions in the cell-cycle.
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Cecilia Williams added:
“Marisa has collected impressive amounts of interesting data. The microarray analysis she performed, whereby she analyzed the effect MELK has on every single gene in our genome’s approximately 23,000 genes, has given us data for the impact of MELK on a global genome level. We are now working to decipher its impact to get a wide and complete understanding of what MELK does in TNBC cells, as well as how we can best use MELK to design better treatments.”
It has also been identified that the MELK protein plays a potential role in the development of other malignancies like prostate cancer, and occurs naturally in both males and females. In addition, MELK also occurs in stem cells and promotes longevity and survival. Researchers believe that if inhibition of MELK emerges as a practical and functional cancer chemotherapeutic treatment, the side effects of radiation and chemotherapy can be largely minimized by replacing these therapies with MELK inhibition.
“I’m interested in medicine and creating new therapies for cancer. I found a mentor with the same passion, and she has allowed me to take part in her work. Through her mentorship and my own research, I have become interested and motivated to pursue finding a genetic therapy for poor-prognosis breast cancer.”
A number of other research studies are also underway which include the role of estrogen in the pathogenesis of breast cancer and microRNA influence on breast cancer metastasis.These initiatives are connected to a large project funded by the National Institutes of Health (NIH) as part of colon cancer research in which microRNAs and estrogen are being used in large development preventive therapies.
“Marisa has been a very good addition to my lab. She is full of enthusiasm, eager to do the work and has contributed to the direction of the project. Her work is extremely relevant to my research of how poor-prognosis breast cancer functions, so that we can better understand how to target this type of cancer in the future.”
Simon presented the research findings on annual Undergraduate Research Day at University of Houston in October on the possible role of MELK in the triple negative breast cancers.