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2. Managing hyperglycemia and rash associated with alpelisib: expert consensus recommendations using the Delphi technique

Author

Gallagher, Emily J., Moore, Heather, Lacouture, Mario E., Dent, Susan F., Farooki, Azeez, Goncalves, Marcus D., Isaacs, Claudine, Johnston, Abigail, Juric, Dejan, Quandt, Zoe, Spring, Laura, Berman, Brian, Decker, Melanie, Hortobagyi, Gabriel N., Kaffenberger, Benjamin H., Kwong, Bernice Y., Pluard, Timothy, Rao, Ruta, Schwartzberg, Lee, and Broder, Michael S.

Published
2024
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4. A multidisciplinary approach to optimizing care of patients treated with alpelisib

Author

Rugo, Hope S, Lacouture, Mario E, Goncalves, Marcus D, Masharani, Umesh, Aapro, Matti S, and O'Shaughnessy, Joyce A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Prevention, Digestive Diseases, Clinical Trials and Supportive Activities, Clinical Research, Cancer, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Female, Humans, Phosphatidylinositol 3-Kinases, Thiazoles, Alpelisib, Breast cancer, PIK3CA, AE management, Public Health and Health Services, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeThe oral, α-specific phosphatidylinositol-3-kinase (PI3Kα) inhibitor alpelisib is the first PI3K inhibitor approved for the treatment of advanced breast cancer. As alpelisib is a relatively new therapeutic option, specific guidance and a multidisciplinary approach are needed to provide optimal patient care. The primary objective of this manuscript is to provide comprehensive guidance on minimizing and managing adverse events (AEs) for patients with advanced breast cancer who are receiving alpelisib.MethodsClinical studies, prescribing information, published literature, and relevant guidelines were reviewed to provide recommendations on the prevention and management of alpelisib-associated AEs.ResultsThe most common AEs associated with alpelisib in the phase 3 SOLAR-1 trial were hyperglycemia and rash (which are considered on-target effects of PI3Kα inhibition) and gastrointestinal AEs, including diarrhea, nausea, and decreased appetite. These AEs require regular monitoring, early recognition, and prompt initiation of appropriate treatment. In addition, there are effective strategies to reduce the onset and severity of frequently observed AEs-in particular, onset of hyperglycemia and rash may be reduced by lifestyle changes (such as reduced intake of carbohydrates and regular exercise) and antihistamine prophylaxis, respectively. To reduce risk of severe hyperglycemia, it is essential to achieve adequate glycemic control prior to initiation of alpelisib treatment.ConclusionOverall, alpelisib-associated AEs are generally manageable with prompt recognition, regular monitoring, and appropriate intervention, preferably with a multidisciplinary approach.

Published
2022

6. Epinephrine inhibits PI3Kα via the Hippo kinases

Author

Lin, Ting-Yu, Ramsamooj, Shakti, Perrier, Tiffany, Liberatore, Katarina, Lantier, Louise, Vasan, Neil, Karukurichi, Kannan, Hwang, Seo-Kyoung, Kesicki, Edward A., Kastenhuber, Edward R., Wiederhold, Thorsten, Yaron, Tomer M., Huntsman, Emily M., Zhu, Mengmeng, Ma, Yilun, Paddock, Marcia N., Zhang, Guoan, Hopkins, Benjamin D., McGuinness, Owen, Schwartz, Robert E., Ersoy, Baran A., Cantley, Lewis C., Johnson, Jared L., and Goncalves, Marcus D.

Published
2023
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9. An atlas of substrate specificities for the human serine/threonine kinome

Author

Johnson, Jared L., Yaron, Tomer M., Huntsman, Emily M., Kerelsky, Alexander, Song, Junho, Regev, Amit, Lin, Ting-Yu, Liberatore, Katarina, Cizin, Daniel M., Cohen, Benjamin M., Vasan, Neil, Ma, Yilun, Krismer, Konstantin, Robles, Jaylissa Torres, van de Kooij, Bert, van Vlimmeren, Anne E., Andrée-Busch, Nicole, Käufer, Norbert F., Dorovkov, Maxim V., Ryazanov, Alexey G., Takagi, Yuichiro, Kastenhuber, Edward R., Goncalves, Marcus D., Hopkins, Benjamin D., Elemento, Olivier, Taatjes, Dylan J., Maucuer, Alexandre, Yamashita, Akio, Degterev, Alexei, Uduman, Mohamed, Lu, Jingyi, Landry, Sean D., Zhang, Bin, Cossentino, Ian, Linding, Rune, Blenis, John, Hornbeck, Peter V., Turk, Benjamin E., Yaffe, Michael B., and Cantley, Lewis C.

Published
2023
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12. A machine learning and network framework to discover new indications for small molecules.

Author

Gilvary, Coryandar, Elkhader, Jamal, Madhukar, Neel, Henchcliffe, Claire, Goncalves, Marcus D, and Elemento, Olivier

Subjects
Antiparkinson Agents, Hypoglycemic Agents, Models, Statistical, Computational Biology, Algorithms, Software, Drug Repositioning, Machine Learning, Models, Statistical, Bioinformatics, Mathematical Sciences, Biological Sciences, Information and Computing Sciences
Abstract

Drug repurposing, identifying novel indications for drugs, bypasses common drug development pitfalls to ultimately deliver therapies to patients faster. However, most repurposing discoveries have been led by anecdotal observations (e.g. Viagra) or experimental-based repurposing screens, which are costly, time-consuming, and imprecise. Recently, more systematic computational approaches have been proposed, however these rely on utilizing the information from the diseases a drug is already approved to treat. This inherently limits the algorithms, making them unusable for investigational molecules. Here, we present a computational approach to drug repurposing, CATNIP, that requires only biological and chemical information of a molecule. CATNIP is trained with 2,576 diverse small molecules and uses 16 different drug similarity features, such as structural, target, or pathway based similarity. This model obtains significant predictive power (AUC = 0.841). Using our model, we created a repurposing network to identify broad scale repurposing opportunities between drug types. By exploiting this network, we identified literature-supported repurposing candidates, such as the use of systemic hormonal preparations for the treatment of respiratory illnesses. Furthermore, we demonstrated that we can use our approach to identify novel uses for defined drug classes. We found that adrenergic uptake inhibitors, specifically amitriptyline and trimipramine, could be potential therapies for Parkinson's disease. Additionally, using CATNIP, we predicted the kinase inhibitor, vandetanib, as a possible treatment for Type 2 Diabetes. Overall, this systematic approach to drug repurposing lays the groundwork to streamline future drug development efforts.

Published
2020

14. Optimal Management of Adverse Events From Copanlisib in the Treatment of Patients With Non-Hodgkin Lymphomas

Author

Cheson, Bruce D, O’Brien, Susan, Ewer, Michael S, Goncalves, Marcus D, Farooki, Azeez, Lenz, Georg, Yu, Anthony, Fisher, Richard I, Zinzani, Pierre L, and Dreyling, Martin

Subjects
Rare Diseases, Cancer, Lymphoma, Cardiovascular, Hematology, Digestive Diseases, Patient Safety, Antineoplastic Agents, Drug-Related Side Effects and Adverse Reactions, Humans, Lymphoma, Non-Hodgkin, Pyrimidines, Quinazolines, Copanlisib, Follicular lymphoma, Hyperglycemia, Hypertension, PI3K, Clinical Sciences, Oncology and Carcinogenesis
Abstract

IntroductionCopanlisib is a phosphoinositol 3-kinase (PI3K) inhibitor approved for the third-line treatment of follicular non-Hodgkin lymphoma. Although the drug is generally well-tolerated, it can be associated with several unique and potentially serious adverse effects (AEs). Two of the most common toxicities not seen with other PI3K inhibitors include hyperglycemia and hypertension, which primarily occur during infusion and resolve shortly thereafter, and likely relate to targeting the PI3K alpha isoform. Other toxicities less commonly observed with copanlisib than with other approved drugs in this class include non-infectious pneumonitis, infections, diarrhea and colitis, and hepatobiliary toxicity.Materials and methodsA panel composed of experts in lymphoma, diabetes, and hypertension convened to develop guidance pertaining to the administration of copanlisib and the management of the AEs associated with copanlisib treatment.ResultsRecommendations were formulated pertaining to the management of AEs associated with copanlisib treatment, particularly infusion-related hyperglycemia and hypertension, noninfectious pneumonitis, infections, diarrhea, and colitis. The recommendations herein reflect the consensus of the members of this panel, all of whom contributed to these suggested approaches to patient supportive care.ConclusionThere are a number of challenges associated with the use of copanlisib. Infusion-related hypertension and hyperglycemia occur frequently, although they are transient, reversible, and rarely of clinical significance; this report provides guidance as to their management.

Published
2019

16. Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer

Author

Langer, Henning Tim, primary, Ramsamooj, Shakti, additional, Dantas, Ezequiel, additional, Murthy, Anirudh, additional, Ahmed, Mujmmail, additional, Ahmed, Tanvir, additional, Hwang, Seo‐Kyoung, additional, Grover, Rahul, additional, Pozovskiy, Rita, additional, Liang, Roger J., additional, Queiroz, Andre Lima, additional, Brown, Justin C., additional, White, Eileen P., additional, Janowitz, Tobias, additional, and Goncalves, Marcus D., additional

Published
2024
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17. Diet and Cancer Metabolism

Author

Locasale, Jason W., primary, Goncalves, Marcus D., additional, Di Tano, Maira, additional, and Burgos-Barragan, Guillermo, additional

Published
2024
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18. Dietary fructose improves intestinal cell survival and nutrient absorption

Author

Taylor, Samuel R., Ramsamooj, Shakti, Liang, Roger J., Katti, Alyna, Pozovskiy, Rita, Vasan, Neil, Hwang, Seo-Kyoung, Nahiyaan, Navid, Francoeur, Nancy J., Schatoff, Emma M., Johnson, Jared L., Shah, Manish A., Dannenberg, Andrew J., Sebra, Robert P., Dow, Lukas E., Cantley, Lewis C., Rhee, Kyu Y., and Goncalves, Marcus D.

Published
2021
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22. Figure 5 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts

Author

Buckbinder, Leonard, primary, St. Jean, David J., primary, Tieu, Trang, primary, Ladd, Brendon, primary, Hilbert, Brendan, primary, Wang, Weixue, primary, Alltucker, Jacob T., primary, Manimala, Samantha, primary, Kryukov, Gregory V., primary, Brooijmans, Natasja, primary, Dowdell, Gregory, primary, Jonsson, Philip, primary, Huff, Michael, primary, Guzman-Perez, Angel, primary, Jackson, Erica L., primary, Goncalves, Marcus D., primary, and Stuart, Darrin D., primary

Published
2023
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23. Data from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts

Author

Buckbinder, Leonard, primary, St. Jean, David J., primary, Tieu, Trang, primary, Ladd, Brendon, primary, Hilbert, Brendan, primary, Wang, Weixue, primary, Alltucker, Jacob T., primary, Manimala, Samantha, primary, Kryukov, Gregory V., primary, Brooijmans, Natasja, primary, Dowdell, Gregory, primary, Jonsson, Philip, primary, Huff, Michael, primary, Guzman-Perez, Angel, primary, Jackson, Erica L., primary, Goncalves, Marcus D., primary, and Stuart, Darrin D., primary

Published
2023
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24. Figure 6 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts

Author

Buckbinder, Leonard, primary, St. Jean, David J., primary, Tieu, Trang, primary, Ladd, Brendon, primary, Hilbert, Brendan, primary, Wang, Weixue, primary, Alltucker, Jacob T., primary, Manimala, Samantha, primary, Kryukov, Gregory V., primary, Brooijmans, Natasja, primary, Dowdell, Gregory, primary, Jonsson, Philip, primary, Huff, Michael, primary, Guzman-Perez, Angel, primary, Jackson, Erica L., primary, Goncalves, Marcus D., primary, and Stuart, Darrin D., primary

Published
2023
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25. Figure 4 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts

Author

Buckbinder, Leonard, primary, St. Jean, David J., primary, Tieu, Trang, primary, Ladd, Brendon, primary, Hilbert, Brendan, primary, Wang, Weixue, primary, Alltucker, Jacob T., primary, Manimala, Samantha, primary, Kryukov, Gregory V., primary, Brooijmans, Natasja, primary, Dowdell, Gregory, primary, Jonsson, Philip, primary, Huff, Michael, primary, Guzman-Perez, Angel, primary, Jackson, Erica L., primary, Goncalves, Marcus D., primary, and Stuart, Darrin D., primary

Published
2023
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26. Figure 1 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts

Author

Buckbinder, Leonard, primary, St. Jean, David J., primary, Tieu, Trang, primary, Ladd, Brendon, primary, Hilbert, Brendan, primary, Wang, Weixue, primary, Alltucker, Jacob T., primary, Manimala, Samantha, primary, Kryukov, Gregory V., primary, Brooijmans, Natasja, primary, Dowdell, Gregory, primary, Jonsson, Philip, primary, Huff, Michael, primary, Guzman-Perez, Angel, primary, Jackson, Erica L., primary, Goncalves, Marcus D., primary, and Stuart, Darrin D., primary

Published
2023
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27. Figure 2 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts

Author

Buckbinder, Leonard, primary, St. Jean, David J., primary, Tieu, Trang, primary, Ladd, Brendon, primary, Hilbert, Brendan, primary, Wang, Weixue, primary, Alltucker, Jacob T., primary, Manimala, Samantha, primary, Kryukov, Gregory V., primary, Brooijmans, Natasja, primary, Dowdell, Gregory, primary, Jonsson, Philip, primary, Huff, Michael, primary, Guzman-Perez, Angel, primary, Jackson, Erica L., primary, Goncalves, Marcus D., primary, and Stuart, Darrin D., primary

Published
2023
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28. Figure 3 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts

Author

Buckbinder, Leonard, primary, St. Jean, David J., primary, Tieu, Trang, primary, Ladd, Brendon, primary, Hilbert, Brendan, primary, Wang, Weixue, primary, Alltucker, Jacob T., primary, Manimala, Samantha, primary, Kryukov, Gregory V., primary, Brooijmans, Natasja, primary, Dowdell, Gregory, primary, Jonsson, Philip, primary, Huff, Michael, primary, Guzman-Perez, Angel, primary, Jackson, Erica L., primary, Goncalves, Marcus D., primary, and Stuart, Darrin D., primary

Published
2023
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29. Supplementary Tables and Figures from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts

Author

Buckbinder, Leonard, primary, St. Jean, David J., primary, Tieu, Trang, primary, Ladd, Brendon, primary, Hilbert, Brendan, primary, Wang, Weixue, primary, Alltucker, Jacob T., primary, Manimala, Samantha, primary, Kryukov, Gregory V., primary, Brooijmans, Natasja, primary, Dowdell, Gregory, primary, Jonsson, Philip, primary, Huff, Michael, primary, Guzman-Perez, Angel, primary, Jackson, Erica L., primary, Goncalves, Marcus D., primary, and Stuart, Darrin D., primary

Published
2023
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32. TIMP1 is an early biomarker for detection and prognosis of lung cancer

Author

Dantas, Ezequiel, primary, Murthy, Anirudh, additional, Ahmed, Tanvir, additional, Ahmed, Mujmmail, additional, Ramsamooj, Shakti, additional, Hurd, Maurice A., additional, Lam, Tiffany, additional, Malbari, Murtaza, additional, Agrusa, Christopher, additional, Elemento, Olivier, additional, Zhang, Chen, additional, Pappin, Darryl J., additional, McGraw, Timothy E., additional, Stiles, Brendon M., additional, Altorki, Nasser K., additional, and Goncalves, Marcus D., additional

Published
2023
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34. Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer

Author

Langer, Henning Tim, primary, Ramsamooj, Shakti, additional, Dantas, Ezequiel, additional, Murthy, Anirudh, additional, Ahmed, Mujmmail, additional, Hwang, Seo-Kyoung, additional, Grover, Rahul, additional, Pozovskiy, Rita, additional, Liang, Roger J., additional, Queiroz, Andre Lima, additional, Brown, Justin C, additional, White, Eileen P., additional, Janowitz, Tobias, additional, and Goncalves, Marcus D., additional

Published
2023
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36. A Study of the Feasibility of FDG-PET/CT to Systematically Detect and Quantify Differential Metabolic Effects of Chronic Tobacco Use in Organs of the Whole Body—A Prospective Pilot Study

Author

Torigian, Drew A., Green-McKenzie, Judith, Liu, Xianling, Shofer, Frances S., Werner, Thomas, Smith, Catherine E., Strasser, Andrew A., Moghbel, Mateen C., Parekh, Ami H., Choi, Grace, Goncalves, Marcus D., Spaccarelli, Natalie, Gholami, Saied, Kumar, Prithvi S., Tong, Yubing, Udupa, Jayaram K., Mesaros, Clementina, and Alavi, Abass

Published
2017
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40. Cachexia: A systemic consequence of progressive, unresolved disease

Author

Ferrer, Miriam, primary, Anthony, Tracy G., additional, Ayres, Janelle S., additional, Biffi, Giulia, additional, Brown, Justin C., additional, Caan, Bette J., additional, Cespedes Feliciano, Elizabeth M., additional, Coll, Anthony P., additional, Dunne, Richard F., additional, Goncalves, Marcus D., additional, Grethlein, Jonas, additional, Heymsfield, Steven B., additional, Hui, Sheng, additional, Jamal-Hanjani, Mariam, additional, Lam, Jie Min, additional, Lewis, David Y., additional, McCandlish, David, additional, Mustian, Karen M., additional, O’Rahilly, Stephen, additional, Perrimon, Norbert, additional, White, Eileen P., additional, and Janowitz, Tobias, additional

Published
2023
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42. A multidisciplinary approach to optimizing care of patients treated with alpelisib

Author

Rugo, Hope S., Lacouture, Mario E., Goncalves, Marcus D., Masharani, Umesh, Aapro, Matti S., and O'Shaughnessy, Joyce A.

Subjects
OGTT, oral glucose tolerance test, Clinical Trials and Supportive Activities, Clinical Sciences, HbA1c, glycosylated hemoglobin, Breast Neoplasms, Review, mTOR, mammalian target of rapamycin, PI3K, phosphatidylinositol-3-kinase, SGLT2i, sodium-glucose co-transporter 2 inhibitor, Alpelisib, Phosphatidylinositol 3-Kinases, AE, adverse events, Breast cancer, PI3Ki, phosphatidylinositol-3-kinase inhibitor, Clinical Research, Antineoplastic Combined Chemotherapy Protocols, IM, intramuscular, Humans, HER2, human epidermal growth factor receptor 2, BID, twice a day, FPG, fasting plasma glucose, FSBG, fingerstick blood glucose, Oncology & Carcinogenesis, RC254-282, Cancer, Prevention, eGFR, estimated glomerular filtration rate, AE management, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, PG, plasma glucose, PIK3CA, General Medicine, GI, gastrointestinal, HR, hazard ratio, TID, thrice daily, SC, subcutaneous, Thiazoles, Public Health and Health Services, PI3Kα, phosphatidylinositol-3-kinase regulatory subunit alpha, Female, Surgery, HR+, hormone receptor-positive, Digestive Diseases, IV, intravenous
Abstract

Purpose The oral, α-specific phosphatidylinositol-3-kinase (PI3Kα) inhibitor alpelisib is the first PI3K inhibitor approved for the treatment of advanced breast cancer. As alpelisib is a relatively new therapeutic option, specific guidance and a multidisciplinary approach are needed to provide optimal patient care. The primary objective of this manuscript is to provide comprehensive guidance on minimizing and managing adverse events (AEs) for patients with advanced breast cancer who are receiving alpelisib. Methods Clinical studies, prescribing information, published literature, and relevant guidelines were reviewed to provide recommendations on the prevention and management of alpelisib-associated AEs. Results The most common AEs associated with alpelisib in the phase 3 SOLAR-1 trial were hyperglycemia and rash (which are considered on-target effects of PI3Kα inhibition) and gastrointestinal AEs, including diarrhea, nausea, and decreased appetite. These AEs require regular monitoring, early recognition, and prompt initiation of appropriate treatment. In addition, there are effective strategies to reduce the onset and severity of frequently observed AEs—in particular, onset of hyperglycemia and rash may be reduced by lifestyle changes (such as reduced intake of carbohydrates and regular exercise) and antihistamine prophylaxis, respectively. To reduce risk of severe hyperglycemia, it is essential to achieve adequate glycemic control prior to initiation of alpelisib treatment. Conclusion Overall, alpelisib-associated AEs are generally manageable with prompt recognition, regular monitoring, and appropriate intervention, preferably with a multidisciplinary approach., Highlights • Alpelisib-associated AEs are generally manageable and reversible • PI3K inhibitor-associated hyperglycemia is an on-target and transient event • Use of prophylactic antihistamines may reduce onset and severity of rash • Enhanced monitoring and management guidance results in fewer drug discontinuations • Further studies are ongoing to optimize management of alpelisib-associated AEs

Published
2022

44. Expert consensus recommendations for managing hyperglycemia and rash in patients with PIK3CA-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) treated with alpelisib (ALP).

Author

Gallagher, Emily J., primary, Moore, Heather, additional, Lacouture, Mario E., additional, Dent, Susan Faye, additional, Farooki, Azeez, additional, Goncalves, Marcus D., additional, Isaacs, Claudine, additional, Johnston, Abigail, additional, Juric, Dejan, additional, Quandt, Zoe, additional, Spring, Laura, additional, Berman, Brian, additional, Decker, Melanie, additional, Hortobagyi, Gabriel N., additional, Kaffenberger, Benjamin, additional, Kwong, Bernice Y., additional, Pluard, Timothy J., additional, Rao, Ruta D., additional, Schwartzberg, Lee S., additional, and Broder, Michael S., additional

Published
2022
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45. Epinephrine inhibits PI3K alpha via the Hippo kinases

Author

Lin, Ting-Yu, primary, Ramsamooj, Shakti, additional, Liberatore, Katarina, additional, Lantier, Louise, additional, Vasan, Neil, additional, Karukurichi, Kannan, additional, Hwang, Seo-Kyoung, additional, Kesicki, Edward A., additional, Kastenhuber, Edward R., additional, Wiederhold, Thorsten, additional, Yaron, Tomer M., additional, Zhu, Mengmeng, additional, Ma, Yilun, additional, Paddock, Marcia N., additional, Zhang, Guoan, additional, Hopkins, Benjamin D., additional, McGuinness, Owen, additional, Schwartz, Robert E., additional, Cantley, Lewis C., additional, Johnson, Jared L., additional, and Goncalves, Marcus D., additional

Published
2022
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46. Targeting insulin feedback to enhance alpelisib (TIFA): A phase II randomized trial in metastatic, PIK3CA-mutant, hormone receptor–positive breast cancer.

Author

Shen, Sherry, primary, Salehi, Erica, additional, Farooki, Azeez, additional, Flory, James, additional, Williams, Dominiq, additional, Carpio, Andrea, additional, Chang, Cassandra, additional, Lacouture, Mario E., additional, Andreopoulou, Eleni, additional, Sardesai, Sagar D., additional, Jhaveri, Komal L., additional, Cantley, Lewis Clayton, additional, Goncalves, Marcus D., additional, and Iyengar, Neil M., additional

Published
2022
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49. A global atlas of substrate specificities for the human serine/threonine kinome

Author

Johnson, Jared L., primary, Yaron, Tomer M., additional, Huntsman, Emily M., additional, Kerelsky, Alexander, additional, Song, Junho, additional, Regev, Amit, additional, Lin, Ting-Yu, additional, Liberatore, Katarina, additional, Cizin, Daniel M., additional, Cohen, Benjamin M., additional, Vasan, Neil, additional, Ma, Yilun, additional, Krismer, Konstantin, additional, Robles, Jaylissa Torres, additional, van de Kooij, Bert, additional, van Vlimmeren, Anne E., additional, Andrée-Busch, Nicole, additional, Käufer, Norbert, additional, Dorovkov, Maxim V., additional, Ryazanov, Alexey G., additional, Takagi, Yuichiro, additional, Kastenhuber, Edward R., additional, Goncalves, Marcus D., additional, Elemento, Olivier, additional, Taatjes, Dylan J., additional, Maucuer, Alexandre, additional, Yamashita, Akio, additional, Degterev, Alexei, additional, Linding, Rune, additional, Blenis, John, additional, Hornbeck, Peter V., additional, Turk, Benjamin E., additional, Yaffe, Michael B., additional, and Cantley, Lewis C., additional

Published
2022
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50. The effects of neoadjuvant chemotherapy and interval debulking surgery on body composition in patients with ovarian cancer

Author

Vitarello, John, Goncalves, Marcus D., Zhou, Qin C., Iasonos, Alexia, Halpenny, Darragh F., Plodkowski, Andrew, Schwitzer, Emily, Mueller, Jennifer J., Zivanovic, Oliver, Jones, Lee W., Cadoo, Karen A., and Konner, Jason A.

Subjects
Article
Abstract

Background The aim of this study was to quantify changes in body composition during ovarian cancer treatment and relate these changes to rates of complete gross resection (CGR). Methods One hundred two patients with stage III or IV ovarian cancer who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery were a part of a prospectively collected database that included computed tomography scans at three time points—diagnosis, following NACT, and following debulking surgery. Skeletal muscle, visceral adipose, and subcutaneous adipose tissue volumes were obtained from a 30-mm volumetric slab beginning at the third lumbar vertebrae. Results Following NACT, skeletal muscle volume was significantly reduced (352.5 to 335.0 cm3, P < 0.001), whereas adiposity was unchanged. Body mass index (BMI) and skeletal muscle volume were significantly lower in patients who achieved CGR (P < 0.05). When these patients were stratified by BMI, the significant association of skeletal muscle to CGR was limited to patients with a BMI < 25 kg/m2 (P = 0.007). Conclusion Skeletal muscle volume was significantly reduced in patients undergoing NACT for ovarian cancer. Non-overweight patients were more likely to achieve CGR if they had lower skeletal muscle volume. Use of volumetric-based measurement for ascertaining body composition should be explored further.

Published
2020

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