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
Shuk On Annie Leung, Olivia Foley, David Chapel, Annacarolina Da Silva, Marisa Nucci, Michael G. Muto, Susana Campos
Summary: Endometrial cancer metastasis to the brain is rare, and molecular analysis plays a crucial role in diagnosis. Comparing the molecular makeup of primary and metastatic lesions can reveal high-risk features indicative of metastatic potential.
Article
Oncology
Min Zhu, Chao Wu, Xuan Wu, Ge Song, Mingyang Li, Qiong Wang
Summary: Our study found that the RNase subunit POP1 is upregulated in breast cancer cell lines and tissues, and higher POP1 expression is associated with poor outcomes. Overexpression of POP1 promotes cell progression in breast cancer cells, while silencing of POP1 induces cell cycle arrest. Mechanistically, POP1 interacts and activates the telomerase complex by stabilizing the telomerase RNA component (TERC), thus protecting telomeres from shortening during division. Overall, our findings suggest that POP1 may serve as a novel prognostic marker and therapeutic target for breast cancer management.
Article
Multidisciplinary Sciences
Motoki Ono, Tsutomu Miyamoto, Ryoichi Asaka, Junko Uchikawa, Hirofumi Ando, Yasuhiro Tanaka, Manaka Shinagawa, Yusuke Yokokawa, Shiho Asaka, Tian-Li Wang, Ie-Ming Shih, Tanri Shiozawa
Summary: This study aimed to create an EAOC mouse model by transplanting uterine pieces from donor mice, in which Arid1a and/or Pten was conditionally knocked out in endometrial cells, onto the ovarian surface or peritoneum of recipient mice. The results showed that induction of only Pten KO evoked atypical endometriosis, while induction of Arid1a; Pten double-KO evoked structures similar to EAOC. This mouse model provides a useful tool for investigating the mechanisms underlying the development of EAOC.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Stuart Turner, Stephen Chia, Hemanth Kanakamedala, Wei-Chun Hsu, Jinhee Park, David Chandiwana, Antonia Ridolfi, Chu-Ling Yu, Juan Pablo Zarate, Hope S. Rugo
Summary: The study compared the efficacy of alpelisib with fulvestrant in the BYLieve trial with standard treatments in a real-world setting for HR+, HER2-, PIK3CA-mutant advanced breast cancer. The results showed that treatment in BYLieve had better outcomes in terms of progression-free survival compared to standard treatments.
Article
Pharmacology & Pharmacy
Hua-Tao Wu, Chun-Lan Li, Ze-Xuan Fang, Wen-Jia Chen, Wen-Ting Lin, Jing Liu
Summary: Triple-negative breast cancer (TNBC) is an aggressive type of breast carcinoma with a high risk of metastasis/relapse and cancer-related death. This study investigated the potential utilization of the mTOR signaling pathway for TNBC treatment by targeting it with itraconazole (ITZ) combined with rapamycin. The results showed that the combination of ITZ and rapamycin synergistically inhibited proliferation and motility of TNBC cells, but did not enhance apoptosis. It was observed that ITZ and/or rapamycin arrested cells in G0/G1 phase and prevented G1/S phase transition. The reduced levels of cyclin D1 protein were consistent with G0/G1 phase arrest, especially when combined with rapamycin.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Tsvetalina Tankova, Elzbieta Senkus, Maria Beloyartseva, Simona Borstnar, Doina Catrinoiu, Mona Frolova, Alinta Hegmane, Andrej Janez, Mladen Krnic, Zoltan Lengyel, Yiola Marcou, Laura Mazilu, Bela Mrinakova, Ruth Percik, Katarina Petrakova, Gabor Rubovszky, Margarita Tokar, Eduard Vrdoljak
Summary: Alpelisib is a drug used to treat a specific type of breast cancer. One of its side effects is an increase in blood glucose levels, which needs to be managed.
Article
Chemistry, Medicinal
Tomohiro Asai, Masafumi Yokota, Hideki Isomura, Hiroyuki Koide, Naoyuki Sakurai, Ayaka Okamoto, Hidenori Ando, Takehisa Dewa, Naoto Oku
Summary: This study explores the synthetic lethal interaction between PTEN loss and PARP1 gene silencing in human triple-negative breast cancer cells. The delivery of siPARP1 using polycation liposomes resulted in cytotoxicity in PTEN-null MDA-MB-468 cells, but not in PTEN-positive MDA-MB-231 cells or normal cells. Simultaneous knockdown of PARP1 and PTEN inhibited cell growth in MDA-MB-231 cells. Furthermore, PARP1 knockdown led to increased DNA breaks and apoptosis in MDA-MB-468 cells compared to MDA-MB-231 cells. These findings suggest that synthetic lethality via PARP1 gene silencing holds promise for the treatment of PTEN-null breast cancer.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Oncology
Kristin Reinhardt, Kathrin Stueckrath, Carolin Hartung, Sandy Kaufhold, Christoph Uleer, Volker Hanf, Tillmann Lantzsch, Susanne Peschel, Jutta John, Marleen Poehler, Marcus Bauer, Friedrich Karl Buerrig, Edith Weigert, Joerg Buchmann, Eva Johanna Kantelhardt, Christoph Thomssen, Martina Vetter
Summary: This study investigated the prevalence of PIK3CA mutations in early stage breast cancer patients and their association with the course of disease. The results showed that PIK3CA mutations were more common in certain types of breast tumors, but did not have a significant association with recurrence-free interval overall. However, in specific subgroups of patients, such as those with hormone receptor-positive breast cancer receiving aromatase inhibitors, PIK3CA mutations were found to have a detrimental impact on prognosis.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Article
Medicine, Research & Experimental
Sushmita Mustafi, Vladimir Camarena, Rehana Qureshi, David W. Sant, Zachary Wilkes, Daniel Bilbao, Joyce Slingerland, Susan B. Kesmodel, Gaofeng Wang
Summary: The study demonstrated that vitamin C can synergistically enhance the anti-cancer effects of buparlisib in treating PIK3CA-mutated triple negative breast cancer cells, leading to reduced dosage requirements and potential mitigation of dose-dependent side effects. Vitamin C modulates PI3K pathway gene expression, inhibits AKT phosphorylation, and works in coordination with buparlisib to inhibit cancer cell growth.
Article
Health Care Sciences & Services
Thomas Bartl, Christoph Grimm, Robert M. Mader, Christoph Zielinski, Gerald Prager, Matthias Unseld, Merima Herac-Kornauth, Alessandro Antonio Buda, Francesco Fanfani
Summary: This exploratory study evaluates the interaction between the mTOR pathway and ER expression in a preclinical cervical cancer model. The results show that ER expression is significantly correlated with phosphorylated-mTOR positive samples and is associated with improved survival in the subgroup of phosphorylated-mTOR positive tumors.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Oncology
Priyanka Tibarewal, Victoria Rathbone, Georgia Constantinou, Wayne Pearce, Mahreen Adil, Zofia Varyova, Lisa Folkes, Alix Hampson, Gala Anastasia Electra Classen, Adriana Alves, Sara Carvalho, Cheryl L. Scudamore, Bart Vanhaesebroeck
Summary: PTEN is an important tumor suppressor gene in cancer, and its deregulation can lead to various cancers. In this study, the authors investigated the potential of the PI3K/mTOR pathway inhibitor rapamycin in preventing cancer in a mouse model of PTEN hamartoma tumor syndrome (PHTS). They found that long-term treatment with low-dose rapamycin significantly improved survival and delayed the development of certain tumors in mice with heterozygous germline Pten loss. This suggests that rapamycin may have cancer prevention potential in human PHTS and other cancers with PI3K pathway activation.
JOURNAL OF PATHOLOGY
(2022)
Article
Cell Biology
Meng-ge Du, Zhi-qiang Peng, Wen-bin Gai, Fan Liu, Wei Liu, Yu-jiao Chen, Hong-chang Li, Xin Zhang, Cui Hua Liu, Ling-qiang Zhang, Hong Jiang, Ping Xie
Summary: The deletion of PTEN in breast cancer cells significantly reduces the anti-tumor efficacy of MLN4924. The activity of the PI3K/Akt signaling pathway correlates positively with UBA3 expression. High glucose conditions upregulate UBA3 mRNA by inhibiting UBA3 promoter methylation, leading to the overactivation of PTEN neddylation in breast cancer cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Tianshi Ma, Mengyu Chai, Huafeng Shou, Guoqing Ru, Ming Zhao
Summary: Mesonephric-like adenocarcinoma (MLA) is a rare and aggressive neoplasm, representing approximately 1% of all endometrial carcinomas. This study aimed to enrich the clinicopathological features of MLA and explore its molecular alterations.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Si Zhou, Songming Liu, Lijian Zhao, Hai-Xi Sun
Summary: This study investigated the signature of neoantigens in breast cancer. PIK3CA gene mutations in breast cancer patients can produce the highest number of neoantigens. SNVs, not indels, are the major source of neoantigens. Patients with hormone receptor-positive or HER2 negative are more likely to produce neoantigens. Age is a significant factor in neoantigen production.
FRONTIERS IN ONCOLOGY
(2022)