Article
Medicine, Research & Experimental
Stefania Cocco, Alessandra Leone, Maria Serena Roca, Rita Lombardi, Michela Piezzo, Roberta Caputo, Chiara Ciardiello, Susan Costantini, Francesca Bruzzese, Maria Jose Sisalli, Alfredo Budillon, Michelino De Laurentiis
Summary: The study found that two PI3K/AKT inhibitors, ipatasertib and taselisib, induced autophagy signaling in different breast cancer models. This effect was particularly evident in PI3K/AKT resistant TNBC cells, where the inhibition of autophagy by CQ potentiated the therapeutic effect of PI3K/AKT inhibitors in vitro and in vivo TNBC models, synergizing with taxane-based chemotherapy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Leiming Wang, Xi Yang, Fei Zhou, Xuesi Sun, Shulin Li
Summary: circUBAP2 promotes cisplatin resistance in TNBC by upregulating ASF1B and activating PI3K/AKT/mTOR signaling.
Article
Biotechnology & Applied Microbiology
Shaoxia Fan, Shen Yan, Yang Yang, Jian Shang, Min Hao
Summary: In this study, it was found that ACTL8 is upregulated in TNBC and is associated with poor prognosis. Silencing ACTL8 inhibited proliferation, migration, and invasion while promoting apoptosis in MDA-MB-231 and BT-549 cells. Additionally, silencing ACTL8 suppressed the activation of the PI3K/AKT/mTOR signaling pathway in these cells, indicating a potential mechanism of ACTL8 in TNBC progression.
ONCOTARGETS AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Yingying Ma, Xiaorong Yang, Hongwei Han, Zhongling Wen, Minkai Yang, Yahan Zhang, Jiangyan Fu, Xuan Wang, Tongming Yin, Guihua Lu, Jinliang Qi, Hongyan Lin, Xiaoming Wang, Yonghua Yang
Summary: This study synthesized a series of anilide (dicarboxylic acid) shikonin esters targeting the PI3K/Akt/mTOR signaling pathway, with compound M9 showing better antiproliferative activity against TNBC cell lines. M9 could potentially be a candidate for TNBC therapy with its ability to inhibit cell proliferation and migration by down-regulating the PI3K/Akt/mTOR signaling pathway.
BIOORGANIC CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Stefano Ratti, Raffaella Mauro, Cristina Rocchi, Sara Mongiorgi, Giulia Ramazzotti, Mauro Gargiulo, Lucia Manzoli, Lucio Cocco, Roberta Fiume
Summary: This review examines the importance of critical enzymes such as PI3K, AKT, and mTOR in the maturation and failure of arteriovenous fistula (AVF) for haemodialysis treatment. These enzymes play a role in various cellular activities and are associated with multiple diseases. They are also druggable targets, which can be targeted to control specific aspects of AVF and provide more personalized therapy.
Article
Multidisciplinary Sciences
Zhenbo Tu, Yi Hu, Devesh Raizada, Mahmoud A. Bassal, Daniel G. Tenen, Antoine E. Karnoub
Summary: This study discovered that the long noncoding RNA LINC01133 plays a protumorigenic role in triple-negative breast cancer (TNBC) and activates AKT through a mTOR Complex 2 (mTORC2)-dependent pathway in a PI3K-independent manner. The antagonism of LINC01133 weakens cellular growth and is associated with poor patient survival in TNBC.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Oncology
Wojciech Wiese, Julia Barczuk, Olga Racinska, Natalia Siwecka, Wioletta Rozpedek-Kaminska, Artur Slupianek, Radoslaw Sierpinski, Ireneusz Majsterek
Summary: The PI3K/Akt/mTOR pathway is crucial in cancer development and can be a potential therapeutic target for leukemia. Recent research indicates that inhibition of this pathway may lead to improved treatment outcomes for leukemia.
Article
Oncology
Shuo Zhang, Tongxing Cui, Yin Duan, Hongchen Zhang, Bei Wang, Huiling Chen, Junjie Ni, Yilin Shen, Xiao-ai Lv
Summary: This study investigated the effect of Radix Tetrastigma extracts (RTEs) on Taxol-induced autophagy and chemosensitivity in triple-negative breast cancer (TNBC). The results showed that RTEs enhanced the chemosensitivity of resistant TNBC cells to Taxol by inhibiting PI3K/Akt/mTOR-mediated autophagy.
CLINICAL BREAST CANCER
(2022)
Review
Biochemistry & Molecular Biology
Eun Jin Sun, Miriam Wankell, Pranavan Palamuthusingam, Craig McFarlane, Lionel Hebbard
Summary: This review article discusses the pivotal role of the PI3K/Akt/mTOR pathway in HCC, focusing on its impact on cellular processes and providing an update on the ongoing clinical development of therapies targeting this pathway for HCC treatments.
Review
Biochemistry & Molecular Biology
Antonino Glaviano, Aaron S. C. Foo, Hiu Y. Lam, Kenneth C. H. Yap, William Jacot, Robert H. Jones, Huiyan Eng, Madhumathy G. Nair, Pooyan Makvandi, Birgit Geoerger, Matthew H. Kulke, Richard D. Baird, Jyothi S. Prabhu, Daniela Carbone, Camilla Pecoraro, Daniel B. L. Teh, Gautam Sethi, Vincenzo Cavalieri, Kevin H. Lin, Nathalie R. Javidi-Sharifi, Eneda Toska, Matthew S. Davids, Jennifer R. Brown, Patrizia Diana, Justin Stebbing, David A. Fruman, Alan P. Kumar
Summary: The PI3K/AKT/mTOR (PAM) signaling pathway plays a crucial role in cell survival, growth, and cell cycle progression. Dysregulation of this pathway is associated with cancer development and resistance to therapy. This review focuses on the major dysregulations in the PAM signaling pathway in cancer and discusses strategies for overcoming treatment resistance. The role of PAM signaling in immunology and immunotherapies is also discussed.
Review
Cell Biology
Kunrui Zhu, Yanqi Wu, Ping He, Yu Fan, Xiaorong Zhong, Hong Zheng, Ting Luo
Summary: Phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) (PAM) pathways play important roles in breast tumorigenesis and offer potential targets for cancer therapy.
Article
Biochemistry & Molecular Biology
Zhonghua An, Xuelin Feng, Mengjia Sun, Yifan Wang, Hongbo Wang, Yanling Gong
Summary: The chemical constituents of chamomile essential oil (CEO) were analyzed using gas chromatography-mass spectrometry (GC/MS). CEO is rich in terpenoids, with Caryophyllene, d-Cadinene, and Caryophyllene oxide as the main components. CEO showed significant antitumor activity by inhibiting the proliferation, migration, and invasion of MDA-MB-231 cells through the inhibition of the PI3K/Akt/mTOR signaling pathway.
CHEMISTRY & BIODIVERSITY
(2023)
Review
Pharmacology & Pharmacy
Nazanin Momeni Roudsari, Naser-Aldin Lashgari, Saeideh Momtaz, Shaghayegh Abaft, Fatemeh Jamali, Pardis Safaiepour, Kiyana Narimisa, Gloria Jackson, Anusha Bishayee, Nima Rezaei, Amir Hossein Abdolghaffari, Anupam Bishayee
Summary: The importance of the PI3K/Akt/mTOR pathway in prostate cancer treatment and the clinical applications of natural agents and small molecule inhibitors targeting this pathway are discussed in the study. Research suggests that natural mTOR inhibitors can interfere with the PI3K/Akt/mTOR pathway through multiple mechanisms, with inhibition of Akt and suppression of mTOR 1 activity being the main therapeutic approaches. Combination therapy has been shown to improve the efficacy of these inhibitors in suppressing prostate cancer progression or overcoming resistance by cancer cells.
Review
Biochemistry & Molecular Biology
Torki A. Zughaibi, Mohd Suhail, Mohammad Tarique, Shams Tabrez
Summary: Cancer is a leading cause of death globally, and current therapies often fail due to side effects, drug resistance, and limited accessibility. Studies have shown that flavonoids, found in herbal/plant sources, may act as complementary treatments for cancer patients with their broad biological properties and anticancer activity by affecting different signaling cascades.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Jieun Bang, Mihyeon Jun, Soyun Lee, Hyuk Moon, Simon Weonsang Ro
Summary: Hepatocellular carcinoma (HCC) is a significant global health concern, with its incidence steadily increasing. Recent progress has been made in understanding the molecular signaling pathways, particularly the EGFR/PI3K/AKT/mTOR pathway, which plays a central role in HCC. Preclinical studies have shown the effectiveness of targeting this signaling pathway for HCC therapy, offering potential therapeutic options for patients.
Article
Oncology
Sayeh M. Lavasani, George Somlo, Susan E. Yost, Paul H. Frankel, Christopher Ruel, Yujie Cui, Mireya Murga, Aileen Tang, Norma Martinez, Laura Kruper, Lusine Tumyan, Daniel Schmolze, Christina Yeon, Yuan Yuan, James R. Waisman, Joanne Mortimer
Summary: This study evaluated the safety and efficacy of nab-paclitaxel, trastuzumab, and pertuzumab as neoadjuvant therapy in patients with HER2+ breast cancer. The results showed a pCR rate of 64% and fewer treatment-associated toxicities, suggesting the possibility of avoiding anthracyclines and carboplatin in this patient population.
Article
Oncology
Siqing Fu, Shuyang Yao, Yuan Yuan, Rebecca A. Previs, Anthony D. Elias, Richard D. Carvajal, Thomas J. George, Ying Yuan, Lihou Yu, Shannon N. Westin, Yan Xing, Ecaterina E. Dumbrava, Daniel D. Karp, Sarina A. Piha-Paul, Apostolia M. Tsimberidou, Jordi Rodon Ahnert, Naoko Takebe, Karen Lu, Khandan Keyomarsi, Funda Meric-Bernstam
Summary: This study aimed to evaluate the antitumor activity of adavosertib in patients with CCNE1-amplified, advanced refractory solid tumors. The results showed that adavosertib demonstrated a manageable toxicity profile and promising clinical activity in patients with CCNE1-amplified refractory solid tumors.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Yuan Yuan, Susan E. Yost, Yujie Cui, Christopher Ruel, Mireya Murga, Aileen Tang, Norma Martinez, Daniel Schmolze, James Waisman, Niki Patel, Lalit Vora, Lusine Tumyan, Mari Bozoghlanian, Daphne Stewart, Paul H. Frankel
Summary: This study evaluated the safety and efficacy of ipatasertib in combination with carboplatin, carboplatin/paclitaxel, or capecitabine/atezolizumab in patients with metastatic triple-negative breast cancer (mTNBC). The primary endpoints were safety and recommended phase II dose (RP2D), while secondary endpoints included progression-free survival (PFS), response rate, and overall survival. The results showed that continuous dosing of ipatasertib with chemotherapy was safe and well-tolerated, and further research is needed to understand the role of AKT inhibition in the treatment of TNBC.
Article
Oncology
Jennifer K. Litton, J. Thaddeus Beck, Jason M. Jones, Jay Andersen, Joanne L. Blum, Lida A. Mina, Raymond Brig, Michael Danso, Yuan Yuan, Antonello Abbattista, Kay Noonan, Alexander Niyazov, Jayeta Chakrabarti, Akos Czibere, William F. Symmans, Melinda L. Telli
Summary: This study evaluates the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC. The results show that talazoparib monotherapy is active in these patients, although the pCR rates did not meet the prespecified threshold. Talazoparib was generally well tolerated.
Article
Oncology
Michael Rainone, Saro Kasparian, Tina Nguyen, Neel Talwar, Yuan Yuan, Matthew Mei, Joanne E. Mortimer, James R. Waisman, Niki Patel, Vinod Pullarkat
Summary: The efficacy of thrombopoietin receptor agonists (TPO-RA) in improving platelet counts due to HER2-targeted antibody-drug conjugate therapy remains unknown. This article reports a case series in which TPO-RA were successfully used to treat thrombocytopenia associated with trastuzumab emtansine and trastuzumab deruxtecan therapy in breast cancer patients. All 6 patients were able to resume therapy with TPO-RA support.
Article
Medicine, General & Internal
Dana Mahin, Sayeh Moazami Lavasani, Leon Cristobal, Niki Tank Patel, Mina Sedrak, Daphne Stewart, James Waisman, Yuan Yuan, Wai Yu, Raynald Samoa, Nora Ruel, Susan E. E. Yost, Hayley Lee, Sung Hee Kil, Joanne E. E. Mortimer
Summary: Glucocorticoids administered with chemotherapy cause hyperglycemia in breast cancer patients. A retrospective study analyzed random blood glucose levels in early-stage breast cancer patients who received dexamethasone prior to chemotherapy. The incidence of steroid-induced hyperglycemia (SIH) was 67%, and it was highest in patients with glucose levels of >200 mg/dL. Non-Hispanic White patients had a higher risk of developing SIH, but over 90% of the patients had transient hyperglycemia.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Cynthia Mark, Jin Sun Lee, Xiaojiang Cui, Yuan Yuan
Summary: Antibody drug conjugates (ADCs) combine monoclonal antibodies with cytotoxic drugs for selective delivery to cancer cells, optimizing treatment effectiveness. ADC research has significantly impacted breast cancer management, providing valuable options. However, important questions remain, such as drug sequencing and overcoming resistance mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Oncology
Erika P. Hamilton, Ololade Dosunmu, Mythili Shastry, Lindsey Finney, Dalila B. Sellami, David W. Sternberg, Vance Wright-Browne, Deborah Toppmeyer, William R. Gwin, J. Thaddeus Thaddeus, Jennifer L. Cultrera, Nusayba Ali Bagegni, Katia Khoury, Arielle Lutterman Heeke, Yuan Yuan
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Meeting Abstract
Oncology
Jamie Green Rand, Dave Yamauchi, Shyambabu Chaurasiya, Jianying Zhang, Raju Pillai, Colt Egelston, Jonathan Kessler, Badri Modi, Leslie Chong, Amanda Seiz, Giovanni Selvaggi, Nick Ede, Mireya Murga, Norma Martinez, Wichanee Borisuthirattana, Hans Meisen, Susan Yost, James Waisman, Daphne Stewart, Joanne Mortimer, Yuman Fong, Yuan Yuan
Meeting Abstract
Oncology
Yara Abdou, E. Claire Dees, Joanne Mortimer, Naoto Ueno, Melissa Johnson, Richard Maziarz, Jennifer Specht, Yuan Yuan, Paula Puhlman, Mathew Angelos, Saar Gill, Amy Ronczka, Thomas Condamine, Daniel J. Cushing, Michael Klichinsky, Debora Barton, Ramona F. Swaby, Kim Reiss Binder
Meeting Abstract
Oncology
Yuan Yuan, Colt A. Egelston, Weihua Guo, Susan E. Yost, Paul H. Frankel, Christopher Ruel, Mireya Murga, Aileen Tang, Norma Martinez, Daniel Schmolze, Daphne Stewart, James Waisman, Kelly Yap, Joanne Mortimer, Niki Tank
Meeting Abstract
Oncology
Yuan Yuan, Jamie G. Rand, Jianying Zhang, Jonathan Kessler, Badri Modi, Raju Pillai, Colt A. Egelston, Shyambabu Chaurasiya, Mireya Murga, Aileen Tang, Norma Martinez, Hans Meisen, Dave Yamauchi, Susan E. Yost, Leslie Chong, Amanda Seiz, Bonnie Nixon, Nick Ede, James Waisman, Daphne Stewart, Mina S. Sedrak, Yuman Fong
Article
Oncology
Yuan Yuan, Susan E. Yost, Yujie Cui, Christopher Ruel, Mireya Murga, Aileen Tang, Norma Martinez, Daniel Schmolze, James Waisman, Niki Patel, Lalit Vora, Lusine Tumyan, Mari Bozoghlanian, Daphne Stewart, Paul H. Frankel
Summary: This trial evaluated the safety and efficacy of ipatasertib in combination with different chemotherapy regimens for metastatic triple-negative breast cancer (mTNBC). The results showed that continuous dosing of ipatasertib with chemotherapy was safe and well-tolerated, and the overall response rates and progression-free survival varied among the different treatment arms. Further study is needed to better understand the role of AKT inhibition in the treatment of TNBCs.