Date of Presentation
5-4-2023 12:00 AM
College
School of Osteopathic Medicine
Poster Abstract
Chemosensory alteration is one of the major side effects of chemotherapy that can negatively impact the quality of life of cancer patients. Decreased appetite and food aversions can consequently lead to substantial reductions in food intake and thereby malnutrition and poor patient outcomes. The chemotherapeutic agent, taxane (docetaxel), is an effective choice of treatment for breast cancer, gastric cancer, or prostate cancer. Despite its major effects as an anti-cancer medication, patients under taxane treatments have reported taste alterations. Essentially, the drug disrupts normal microtubule growth by inhibiting microtubule depolymerization. By binding to ß-tubulin, a major component of mitotic spindles, docetaxel (DTX) hyper-stabilizes the microtubule structure, rendering it incapable of properly shortening and elongating. This intrinsic property is especially crucial for chromosome segregation during cell division. DTX also causes apoptosis and peripheral neuropathy. Further, microtubules are essential components of cilia, where Hedgehog (HH) signaling takes place. HH signaling plays a critical regulatory role in taste organ formation and maintenance, while its deregulation can severely disrupt taste perception. Importantly, taxane-based therapies have demonstrated an upregulating effect on HH signaling, but in combination therapies such as with sodium butyrate, it exhibits a down regulating effect. It might be possible that the DTX is causing taste alterations via changes in HH signaling. Alternatively, disruption of cell division can also result in changes in taste cell turnover. The aim of this study is to elucidate whether DTX has an indirect or direct effect on the taste organ and whether it alters HH signaling.
Keywords
Neoplasms, Antineoplastic Agents, Dysgeusia, Animal Models
Disciplines
Medicine and Health Sciences | Neoplasms | Oncology
Document Type
Poster
Included in
Evaluating the Effect of a Taxane-Based Anti-Cancer Drug on the Adult Taste Organ Using a Mouse Model
Chemosensory alteration is one of the major side effects of chemotherapy that can negatively impact the quality of life of cancer patients. Decreased appetite and food aversions can consequently lead to substantial reductions in food intake and thereby malnutrition and poor patient outcomes. The chemotherapeutic agent, taxane (docetaxel), is an effective choice of treatment for breast cancer, gastric cancer, or prostate cancer. Despite its major effects as an anti-cancer medication, patients under taxane treatments have reported taste alterations. Essentially, the drug disrupts normal microtubule growth by inhibiting microtubule depolymerization. By binding to ß-tubulin, a major component of mitotic spindles, docetaxel (DTX) hyper-stabilizes the microtubule structure, rendering it incapable of properly shortening and elongating. This intrinsic property is especially crucial for chromosome segregation during cell division. DTX also causes apoptosis and peripheral neuropathy. Further, microtubules are essential components of cilia, where Hedgehog (HH) signaling takes place. HH signaling plays a critical regulatory role in taste organ formation and maintenance, while its deregulation can severely disrupt taste perception. Importantly, taxane-based therapies have demonstrated an upregulating effect on HH signaling, but in combination therapies such as with sodium butyrate, it exhibits a down regulating effect. It might be possible that the DTX is causing taste alterations via changes in HH signaling. Alternatively, disruption of cell division can also result in changes in taste cell turnover. The aim of this study is to elucidate whether DTX has an indirect or direct effect on the taste organ and whether it alters HH signaling.