Article
Oncology
Wei-Pang Chung, Wei-Lun Huang, Chun-Hui Lee, Hui-Ping Hsu, Wan-Ling Huang, You-Yu Liu, Wu-Chou Su
Summary: The activation of the PI3K signaling pathway is associated with the development and resistance of breast cancer. Mutations in PIK3CA and loss of PTEN occur in all subtypes of breast cancer. The combination of PI3K inhibitors and trastuzumab shows potential in treating HER2-positive breast cancer, but its effectiveness in HER2-positive breast cancer with PIK3CA mutations and/or PTEN loss is still unclear. In this study, a novel alpha isoform-specific PI3K inhibitor was shown to effectively target breast cancer cells with PIK3CA mutations or PTEN deficiency when combined with trastuzumab. The combination therapy was found to be ineffective in breast cancer cells without PI3K pathway alterations, indicating a biomarker-specific treatment. In vivo testing in a mouse model confirmed the efficacy of the combination therapy in reducing tumor volume. This cytotoxic chemotherapy-free regimen, as a biomarker-driven strategy, warrants further investigation for the treatment of HER2-positive breast cancer.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
Maria Letizia Cataldo, Pietro De Placido, Daniela Esposito, Luigi Formisano, Grazia Arpino, Mario Giuliano, Roberto Bianco, Carmine De Angelis, Bianca Maria Veneziani
Summary: This study investigated the antitumor efficacy of the alpha-specific PI3K inhibitor alpelisib alone or in combination with anti-HER2 therapy in HER2-positive breast cancer. Models of acquired resistance to alpelisib were also generated to understand the mechanisms underlying resistance to alpha-specific PI3K inhibition.
FRONTIERS IN ONCOLOGY
(2023)
Review
Gastroenterology & Hepatology
Hayato Kurihara, Cecilia Binda, Matteo Maria Cimino, Raffaele Manta, Guido Manfredi, Andrea Anderloni
Summary: Acute cholecystitis is a common disease in clinical practice. Laparoscopic cholecystectomy is the standard treatment, but it may be too risky for certain patients. Non-operative treatments such as percutaneous gallbladder drainage, endoscopic transpapillary gallbladder drainage, and EUS-guided drainage can be effective alternatives. These options should be considered in a stepwise approach after an accurate evaluation in a multidisciplinary discussion.
DIGESTIVE AND LIVER DISEASE
(2023)
Article
Virology
Ye Wei, Shitong Lin, Wenhua Zhi, Tian Chu, Binghan Liu, Ting Peng, Miaochun Xu, Wencheng Ding, Canhui Cao, Peng Wu
Summary: Cervical carcinoma is a serious gynecological cancer with potential targets in the PI3K/AKT pathways. The study found that PIK3CA mutation is common in cervical carcinoma, and Alpelisib can inhibit the growth of PIK3CA-mutant cancer cells and enhance cisplatin efficacy. This study provides insights into the potential use of Alpelisib in precision medicine for cervical carcinoma.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Oncology
Alessio Fiascarelli, Giuseppe Merlino, Stefania Capano, Simone Talucci, Diego Bisignano, Alessandro Bressan, Daniela Bellarosa, Corrado Carrisi, Alessandro Paoli, Mario Bigioni, Patrizia Tunici, Clelia Irrissuto, Massimiliano Salerno, Joaquin Arribas, Elisa de Stanchina, Maurizio Scaltriti, Monica Binaschi
Summary: The activity of the PI3K inhibitor MEN1611 was investigated in HER2+ breast cancer models and compared to other PI3K inhibitors. MEN1611 showed different cytotoxic activity and selectively decreased p110 alpha protein levels in PIK3CA mutated breast cancer cells. In vivo, MEN1611 exhibited significant antitumor activity, especially in combination with trastuzumab, in trastuzumab-resistant PIK3CA-mutant HER2+ breast cancer models.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Chemistry, Medicinal
Emily J. Hanan, Marie-Gabrielle Braun, Robert A. Heald, Calum MacLeod, Connie Chan, Saundra Clausen, Kyle A. Edgar, Charles Eigenbrot, Richard Elliott, Nicholas Endres, Lori S. Friedman, Emily Gogol, Xiao-Hui Gu, Rebecca Hong Thibodeau, Philip S. Jackson, James R. Kiefer, Jamie D. Knight, Michelle Nannini, Raman Narukulla, Amanda Pace, Jodie Pang, Hans E. Purkey, Laurent Salphati, Deepak Sampath, Stephen Schmidt, Steve Sideris, Kyung Song, Swathi Sujatha-Bhaskar, Mark Ultsch, Heidi Wallweber, Jianfeng Xin, SiewKuen Yeap, Amy Young, Yu Zhong, Steven T. Staben
Summary: This study optimized a series of benzoxazepin-oxazolidinone ATP-competitive inhibitors of PI3K alpha that also induce selective degradation of the mutant p110 alpha protein. Structure-based design led to potent inhibitors with over 300-fold selectivity and further optimization of pharmacokinetic properties resulted in excellent in vivo efficacy. Clinical candidate GDC-0077 (inavolisib) is now being evaluated in a Phase III clinical trial for treating patients with PIK3CA-mutant breast cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Justus Rosin, Ella Svegrup, Antonios Valachis, Ioannis Zerdes
Summary: This meta-analysis indicates that there is a discordance in PIK3CA mutational status between primary and metastatic breast tumors. The overall discordance rate is 9.8% and the change is bi-directional, with more cases transitioning from mutated to wild-type status.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Chemistry, Medicinal
Jindi Huang, Liye Chen, Jiangxia Wu, Daiqiao Ai, Ji-Quan Zhang, Tie-Gen Chen, Ling Wang
Summary: The PI3K/AKT/mTOR pathway plays a crucial role in cell proliferation, growth, differentiation, and survival. Developing novel drugs targeting this pathway is of great importance for treating various diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Albert Gris-Oliver, Yasir H. Ibrahim, Martin A. Rivas, Celina Garcia-Garcia, Monica Sanchez-Guixe, Fiorella Ruiz-Pace, Cristina Viaplana, Jose M. Perez-Garcia, Antonio Llombart-Cussac, Judit Grueso, Mireia Pares, Marta Guzman, Olga Rodriguez, Pilar Anton, Patricia Cozar, Maria Teresa Calvo, Alejandra Bruna, Joaquin Arribas, Carlos Caldas, Rodrigo Dienstmann, Paolo Nuciforo, Mafalda Oliveira, Javier Cortes, Violeta Serra
Summary: The study found that 64% of resistant models in HER2- BC cell lines and patient-derived xenografts carried mutations in PIK3CA, PIK3R1, or AKT1, compared to only 17% in sensitive models, indicating a correlation between mutations in the PI3K/AKT pathway and resistance to eribulin. The addition of PI3K inhibitors can reverse primary and acquired resistance to eribulin, regardless of genetic alterations in the PI3K/AKT pathway or ER status, suggesting that PI3K pathway activation may induce primary resistance or early adaptation to eribulin.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Hui Dang, Mengjun Sui, Qingyuan He, Jingyi Xie, Yan Liu, Peng Hou, Meiju Ji
Summary: This study shows that Pin1 inhibitor API-1 has strong antitumor activity against thyroid cancer and improves the sensitivity of BRAF-mutant thyroid cancer cells to BRAF inhibitor PLX4032. The combination therapy of API-1 and PLX4032 offers an alternative therapeutic strategy for BRAF-mutant thyroid cancers.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Oncology
Sakthisri Krishnamurthy, Hiroyuki Yoda, Kiriko Hiraoka, Takahiro Inoue, Jason Lin, Yoshinao Shinozaki, Takayoshi Watanabe, Nobuko Koshikawa, Atsushi Takatori, Hiroki Nagase
Summary: The novel pyrrole-imidazole polyamide-seco-CBI conjugate P3AE5K effectively targeted PIK3CA mutant cells in cervical cancer, demonstrating strong cytotoxicity and the potential to be a promising new drug candidate.
Article
Oncology
Dimitrios Prassas, Sami Alexander Safi, Maria Chara Stylianidi, Leila Anne Telan, Sarah Krieg, Christoph Roderburg, Irene Esposito, Tom Luedde, Wolfram Trudo Knoefel, Andreas Krieg
Summary: In patients with resected pancreatic ductal adenocarcinoma (PDAC), a study compared different lymph node classification schemes and found that one LNR and one LODDS classification scheme out-performed the N category in terms of prognostic performance and discriminative ability, particularly in distinct patient subgroups.
Review
Oncology
Carmen Belli, Matteo Repetto, Santosh Anand, Camillo Porta, Vivek Subbiah, Giuseppe Curigliano
Summary: Phosphoinositide 3-kinases (PI3Ks) play a crucial role in tumorigenesis, particularly the p110 alpha subunit (PIK3CA) with activating mutations found in various tumors. Current PI3K inhibitors have limited efficacy due to on-target toxicity, inhibiting both wild-type and mutant PI3Ks. However, the development of mutant and isoform selective PIK3CA inhibitors has surged interest in targeting PIK3CA in solid tumors. This review summarizes the understanding of PI3K alterations, treatment strategies, and emerging resistance mechanisms and the role of mutant selective PIK3CA inhibitors.
BRITISH JOURNAL OF CANCER
(2023)
Article
Medicine, General & Internal
Jakub Okulski, Marcin Kozakiewicz, Michal Krasowski, Rafal Zielinski, Tomasz Wach
Summary: This study compares the mechanical strength of different plate designs for low-neck fractures. The XCP side-dedicated 3+5 and ACP-T plates demonstrated strength comparable to two straight plates. The introduced Mechanical Excellence Factor (MEF) provides a more accurate metric for predicting a plate's mechanical strength.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Chemistry, Medicinal
Mingliang Zhu, Qiuyang Jin, Yizhou Xin
Summary: The PI3K/Akt/mTOR signaling pathway plays a crucial role in regulating cell cycle and tumor angiogenesis, with inhibitors targeting PI3K showing positive effects in the treatment of breast and colorectal cancer.