To millions around the world, the word ‘cancer’ evokes emotions of sorrow and fear. For decades, scientists around the world have been trying to combat this disease, but to no avail. Despite the best efforts of modern medicine, about 46% of patients diagnosed with cancer still pass away as a direct result of the disease.1 However, the research performed by Dr. Michael Gustin at Rice University may change the field of oncology forever.
Cancer is a complex and multifaceted disease that is currently not fully understood by medical doctors and scientists. Tumors vary considerably between different types of cancers and from patient to patient, further complicating the problem. Understanding how cancer develops and responds to stimuli is essential to producing a viable cure, or even an individualized treatment.
Dr. Gustin’s research delves into the heart of this problem. The complexity of the human body and its component cells are currently beyond the scope of any one unifying model. For this reason, starting basic research with human subjects would be detrimental. Researchers turn instead to simpler eukaryotes in order to understand the signal pathways involved in the cell cycle and how they respond to stress.2 Through years of hard work and research, Dr. Gustin’s studies have made huge contributions to the field of oncology.
Dr. Gustin studied a species of yeast, Saccharomyces cerevisiae, and its response to osmolarity. His research uncovered the high osmolarity glycerol (HOG) pathway and mitogen-activated protein kinase (MAPK) cascade, which work together to maintain cellular homeostasis. The HOG pathway is much like a “switchboard [that] control[s] cellular behavior and survival within a cell, which is regulated by the MAPK cascade through the sequential phosphorylation of a series of protein kinases that mediates the stress response.”3 These combined processes allow the cell to respond to extracellular stress by regulating gene expression, cell proliferation, and cell survival and apoptosis. To activate the transduction pathway, the sensor protein Sln1 recognizes a stressor and subsequently phosphorylates, or activates, a receiver protein that mediates the cellular response. This signal transduction pathway leads to the many responses that protect a cell against external stressors. These same protective processes, however, allow cancer cells to shield themselves from the body’s immune system, making them much more difficult to attack.
Dr. Gustin has used this new understanding of the HOG pathway to expand his research into similar pathways in other organisms. Fascinatingly, the expression of human orthologs of HOG1 proteins within yeast cells resulted in the same stimulation of the pathway despite the vast evolutionary differences between yeast and mammals. Beyond the evolutionary implications of this research, this illustrates that the “[HOG] pathway defines a central stress response signaling network for all eukaryotic organisms”.3 So much has already been learned through studies on Saccharomyces cerevisiae and yet researchers have recently discovered an even more representative organism. This fungus, Candida albicans, is the new model under study by Dr. Gustin and serves as the next step towards producing a working model of cancer and its responses to stressors. Its more complex responses to signalling make it a better working model than Saccharomyces cerevisiae.4 The research that has been conducted on Candida albicans has already contributed to the research community’s wealth of information, taking great strides towards eventual human applications in the field of medicine. For example, biological therapeutics designed to combating breast cancer cells have already been tested on both Candida albicans biofilms and breast cancer cells to great success.5
This research could eventually be applied towards improving current chemotherapy techniques for cancer treatment. Eventual applications of this research are heavily oriented towards fighting cancer through the use of chemotherapy techniques. Current chemotherapy techniques utilize cytotoxic chemicals that damage and kill cancerous cells, thereby controlling the size and spread of tumors. Many of these drugs can disrupt the cell cycle, preventing the cancerous cell from proliferating efficiently. Alternatively, a more aggressive treatment can induce apoptosis, programmed cell death, within the cancerous cell.6 For both methods, the chemotherapy targets the signal pathways that control the vital processes of the cancer cell. Dr. Gustin’s research plays a vital role in future chemotherapy technologies and the struggle against mutant cancer cells.
According to Dr. Gustin, current chemotherapy is only effective locally, and often fails to completely incapacitate cancer cells that are farther away from the site of drug administration where drug toxicity is highest. As a result, distant cancer cells are given the opportunity to develop cytoprotective mechanisms that increase their resistance to the drug.7 Currently, a major goal of Dr. Gustin’s research is to discover how and why certain cancer cells are more resistant to chemotherapy. The long-term goal is to understand the major pathways involved with cancer resistance to apoptosis, and to eventually produce a therapeutic product that can target the crucial pathways and inhibitors. With its specificity, this new drug would vastly increase treatment efficacy and provide humanity with a vital tool with which to combat cancer, saving countless lives in the future.
- American Cancer Society. https://www.cancer.org/latest-new/cancer-facts-and-figures-death-rate-down-25-since-1991.html (February 3 2017).
- Radmaneshfar, E.; Kaloriti, D.; Gustin, M.; Gow, N.; Brown, A.; Grebogi, C.; Thiel, M. Plos ONE, 2013, 8, e86067.
- Brewster, J.; Gustin, M. Sci. Signal. 2014, 7, re7.
- Rocha, C.R.; Schröppel, K.; Harcus, D.; Marcil, A.; Dignard, D.; Taylor, B.N.; Thomas, D.Y.; Whiteway, M.; Leberer, E. Mol. Biol. Cell. 2001, 12, 3631-3643.
- Malaikozhundan, B.; Vaseeharan, B.; Vijayakumar, S.; Pandiselvi K.; Kalanjiam R.; Murugan K.; Benelli G. Microbial Pathogenesis 2017, 102, n.p. Manuscript in progress.
- Shapiro, G. and Harper, J.; J Clin Invest. 1999, 104, 1645–1653.
- Das, B.; Yeger, H.; Baruchel, H.; Freedman, M.H.; Koren, G.; Baruchel, S. Eur. J. Cancer. 2003, 39, 2556-2565.