Article
Biology
Abdulkadir Elmas, Serena Tharakan, Suraj Jaladanki, Matthew D. Galsky, Tao Liu, Kuan-lin Huang
Summary: Elmas et al. developed the OPPTI algorithm to identify overexpressed kinase proteins in multiple cancer types using global mass spectrometry proteomics data. They found that protein-level abnormalities, which are sometimes not observed by genomics, represent vulnerabilities in cancer that could be targeted for precision oncology. The study showed that proteomic analysis can reveal new treatment opportunities and validate genomic alterations in cancer proteins.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Werner Theodor Jauslin, Matthias Schild, Thorsten Schaefer, Chiara Borsari, Clara Orbegozo, Lukas Bissegger, Saule Zhanybekova, Danilo Ritz, Alexander Schmidt, Matthias Wymann, Dennis Gillingham
Summary: This study presents a new approach to selectively degrade the frequently mutated isoform PI3K alpha by incorporating a high affinity binding module and a cereblon-targeted degrader. Through systematic proteomics study, the researchers optimized the selectivity and potency of the degrader, resulting in the creation of WJ112-14, a PI3K alpha-specific nanomolar degrader. This research offers a new method for selectively targeting the frequently mutated oncogenic driver.
Article
Oncology
Peter Savas, Louisa L. Lo, Stephen J. Luen, Elizabeth F. Blackley, Jason Callahan, Kate Moodie, Courtney T. van Geelen, Yi-An Ko, Chen -Fang Weng, Lironne Wein, Maria Joao Silva, Andjelija Zivanovic Bujak, Miriam M. Yeung, Sarah Ftouni, Rodney J. Hicks, Prudence A. Francis, Chee Khoon Lee, Sarah -Jane Dawson, Sherene Loi
Summary: Alpelisib monotherapy demonstrated efficacy in heavily pretreated ER + breast cancer, and the dynamics of PIK3CA mutation and ESR1 mutation detected in plasma can serve as candidate biomarkers for predicting treatment response.
Article
Cell Biology
Sho Isoyama, Naomi Tamaki, Yutaka Noguchi, Mutsumi Okamura, Yuki Yoshimatsu, Tadashi Kondo, Takeshi Suzuki, Shin-ichi Yaguchi, Shingo Dan
Summary: This study demonstrated the anti-tumor effect of PI3K inhibitors and their ability to induce apoptosis in specific TRS subtypes such as ES and SS through the induction of PUMA and BIM expression and the loss of mitochondrial membrane potential. However, other TRS subtypes and non-TRS cell lines did not exhibit apoptosis in response to PI3K inhibitors.
CELL DEATH & DISEASE
(2023)
Article
Chemistry, Medicinal
Robin Warstat, Mehrosh Pervaiz, Pierre Regenass, Marius Amann, Karin Schmidtkunz, Oliver Einsle, Manfred Jung, Bernhard Breit, Martin Huegle, Stefan Guenther
Summary: For a long time, BD inhibitors were mainly related to the BET family, but now inhibitors for BDs outside the BET family have been developed. We present a new pan-BD inhibitor that shows affinity to various BDs and exhibits broad activity against different cancer cell lines. Through modifications, we were able to control the selectivity of the inhibitor and make it a highly selective BRD9 inhibitor.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ingrid Fatima Zattoni, Thales Kronenberger, Diogo Henrique Kita, Lais Danciguer Guanaes, Matheus Murmel Guimaraes, Larissa de Oliveira Prado, Melanie Ziasch, Luis C. Vesga, Fabiane Gomes de Moraes Rego, Geraldo Picheth, Marcos Brown Goncalves, Miguel D. Noseda, Diogo R. B. Ducatti, Antti Poso, Robert W. Robey, Suresh Ambudkar, Vivian Rotuno Moure, Alan Guilherme Goncalves, Glaucio Valdameri
Summary: A newly discovered porphyrin derivative (4B) was identified as an inhibitor of the ABCG2 transporter, capable of overcoming multidrug resistance in vitro and showing selective inhibition towards ABCG2 without being transported by it.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Oncology
Parham Jabbarzadeh Kaboli, Saber Imani, Masume Jomhori, King-Hwa Ling
Summary: Breast cancer displays poor response to conventional chemotherapy due to the activation of Akt signaling, which is considered a key factor in intrinsic and acquired drug resistance. Akt signaling not only enhances multi-drug resistance, but also plays crucial roles in cellular metabolism, apoptosis, and other processes.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Ninghui Mao, Zeda Zhang, Young Sun Lee, Danielle Choi, Aura Agudelo Rivera, Dan Li, Cindy Lee, Samuel Haywood, Xiaoping Chen, Qing Chang, Guotai Xu, Hsuan-An Chen, Elisa de Stanchina, Charles Sawyers, Neal Rosen, Andrew C. Hsieh, Yu Chen, Brett S. Carver
Summary: Understanding the mechanisms driving PI3K isoform dependency in prostate cancer can help in designing effective clinical trials. Mutations in PIK3CA or PIK3CB can result in PI3K p110 isoform dependency, with direct inhibition of AKT potentially being more effective than PI3K inhibition in PTEN-deficient prostate cancers. Selective targeting of specific PI3K isoforms based on contextual factors like PTEN status and PIK3CA/PIK3CB alterations may offer novel therapeutic strategies.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Zijie Cai, Jingru Wang, Yudong Li, Qianfeng Shi, Liang Jin, Shunying Li, Mengdi Zhu, Qi Wang, Lok Lam Wong, Wang Yang, Hongna Lai, Chang Gong, Yandan Yao, Yujie Liu, Jun Zhang, Herui Yao, Qiang Liu
Summary: CDK4/6 inhibitors are standard treatment for advanced HR+/HER2- breast cancer, but resistance is inevitable. This study found that overexpression of Cyclin D1 and CDK4 proteins leads to resistance, and targeting the PI3K/mTOR pathway can restore sensitivity.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Article
Chemistry, Applied
Zhiqing Zhang, Ziheng Zhao, Dongli Tan, Yanshuai Ye, Bin Zhang, Bo Huang, Weihuang Zhong, Jian Zhang, Jingyi Hu
Summary: This review provides a detailed summary of the mechanism of water's effect on SCR reactions, discussing the impact of reaction conditions and catalyst types on SCR reactions and catalysts, and collating improvement strategies to enhance the activity and water resistance of SCR catalysts.
FUEL PROCESSING TECHNOLOGY
(2023)
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
Cell Biology
Haiyan Yang, Zhi Li, Zhangwei Wang, Xu Zhang, Xinyuan Dai, Guoren Zhou, Qiang Ding
Summary: The study found that HM13 is highly expressed in breast cancer and is associated with poor prognosis. Downregulation of HM13 can suppress the proliferation and metastasis abilities of breast cancer cells, activate autophagy, and inhibit the PI3K-AKT-mTOR pathway. It was also discovered that miR-760 directly targets HM13 and has tumor-suppressive effects in breast cancer.
CELL DEATH & DISEASE
(2022)
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)
Review
Pharmacology & Pharmacy
Davide Cirillo, Marta Diceglie, Marc Nazare
Summary: Phosphoinositide-3-kinases (PI3Ks) play a central role in various cellular signaling pathways and are potential targets for pharmacological treatment of diseases such as cancer, thrombosis, and pulmonary diseases. Isoform-selective inhibitors have been developed and approved, but challenges regarding drug tolerance have been observed. Therefore, additional approaches are needed, including targeting underexplored PI3K class II isoforms, to enhance the clinical benefits of specific treatment options. This review highlights recent discoveries in isoform-selective inhibitors, with a focus on PI3K class II isoforms, and emphasizes the importance of developing a broader arsenal of pharmacological tools.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Review
Genetics & Heredity
Zhengxuan Han, You Wang, Lei Han, Chaogang Yang
Summary: Oncogenes and tumor suppressor genes play a crucial role in regulating tumor phenotype in human cancers. RPN2, a known oncogene, encodes a protein that is part of an N-oligosaccharyl transferase, and is found to be abnormally expressed in various human malignancies. Accumulating evidence shows that RPN2 contributes to tumorigenicity, metastasis, progression, and drug resistance by affecting N-glycosylation and multiple signaling pathways.
Article
Cell Biology
Yi Xiao, Ding Ma, Yun-Song Yang, Fan Yang, Jia-Han Ding, Yue Gong, Lin Jiang, Li-Ping Ge, Song-Yang Wu, Qiang Yu, Qing Zhang, Francois Bertucci, Qiuzhuang Sun, Xin Hu, Da-Qiang Li, Zhi-Ming Shao, Yi-Zhou Jiang
Summary: Metabolic reprogramming in triple-negative breast cancer (TNBC) was systematically characterized in this study, resulting in the construction of a large metabolomic atlas. The study classified TNBCs into three distinct metabolomic subgroups and identified subtype-specific metabolites as potential therapeutic targets. The findings suggest the clinical significance of TNBC metabolomics and provide valuable resources for precision treatment of TNBC.
Article
Oncology
Alexia Lopresti, Claire Acquaviva, Laurys Boudin, Pascal Finetti, Severine Garnier, Anais Aulas, Maria Lucia Liberatoscioli, Olivier Cabaud, Arnaud Guille, Alexandre de Nonneville, Quentin Da Costa, Emilie Denicolai, Jihane Pakradouni, Anthony Goncalves, Daniel Birnbaum, Francois Bertucci, Emilie Mamessier
Summary: In this study, atypical cells in the blood of metastatic breast cancer patients were isolated and analyzed using a micro-filtration technic. Three subsets of circulating tumor cells were identified, each with different prognostic values. Moreover, a subset of CTCs was found to be a potential stratification tool for selecting patients for early clinical trials. This study highlights the heterogeneity of CTCs and their potential as a non-invasive tool for precision medicine.
Article
Oncology
Emilien Billon, Gwenaelle Gravis, Arnaud Guille, Nadine Carbuccia, Jose Adelaide, Severine Garnier, Pascal Finetti, Emilie Denicolai, Patrick Sfumato, Serge Brunelle, Jeanne Thomassin-Piana, Geraldine Pignot, Jochen Walz, Christian Chabannon, Jihane Pakradouni, Renaud Sabatier, Cecile Vicier, Cornel Popovici, Emilie Mamessier, Anthony Goncalves, Daniel Birnbaum, Max Chaffanet, Francois Bertucci
Summary: This study identified actionable genetic alterations in advanced urological cancers through molecular profiling of tumor samples. Patients who received matched therapy based on the identified alterations showed higher disease control rates and overall survival.
Article
Oncology
Yohan Fayet, Christine Chevreau, Gauthier Decanter, Cecile Dalban, Pierre Meeus, Sebastien Carrere, Leila Haddag-Miliani, Francois Le Loarer, Sylvain Causeret, Daniel Orbach, Michelle Kind, Louis-Romee Le Nail, Gwenael Ferron, Helene Labrosse, Loic Chaigneau, Francois Bertucci, Jean-Christophe Ruzic, Valerie Le Brun Ly, Fadila Farsi, Emmanuelle Bompas, Sabine Noal, Aurore Vozy, Agnes Ducoulombier, Clement Bonnet, Sylvie Chabaud, Francoise Ducimetiere, Camille Tlemsani, Mickael Ropars, Olivier Collard, Paul Michelin, Justine Gantzer, Pascale Dubray-Longeras, Maria Rios, Pauline Soibinet, Axel Le Cesne, Florence Duffaud, Marie Karanian, Francois Gouin, Raphael Tetreau, Charles Honore, Jean-Michel Coindre, Isabelle Ray-Coquard, Sylvie Bonvalot, Jean-Yves Blay
Summary: The study assesses the potential of reference networks in reducing geographical inequalities in cancer management for patients with sarcoma. The national reference network NETSARC+ provides remote specialized diagnosis and Multidisciplinary Tumour Board to improve sarcoma patients' management and survival in France. The analysis shows no association between overall survival and geographical variables, suggesting the ability of the organization to overcome geographical barriers and enhance cancer management.
Article
Oncology
Alexandre de Nonneville, Pascal Finetti, Maelle Picard, Audrey Monneur, Maria Abbondanza Pantaleo, Annalisa Astolfi, Jerzy Ostrowski, Daniel Birnbaum, Emilie Mamessier, Francois Bertucci
Summary: Gastrointestinal stromal tumors (GIST) are the most frequent sarcomas of the gastrointestinal tract. This study found that high expression of cell surface proteoglycan CSPG4 in GIST is associated with better disease-free survival and an immune environment favorable to cytotoxic immune response. These findings suggest the potential value of CSPG4-specific chimeric antigen receptor-redirected cytokine-induced killer lymphocytes treatment in GIST, especially in CSPG4-high tumors, and calls for further validation and clinical trials.
Article
Oncology
C. Moreau-Bachelard, L. Campion, M. Toulmonde, A. Le Cesne, M. Brahmi, A. Italiano, O. Mir, S. Piperno-Neumann, V Laurence, N. Firmin, N. Penel, F. Duffaud, C. Chevreau, F. Bertucci, B. Narciso, P. Dubray-Longeras, C. Delcambre, E. Saada-Bouzid, P. Boudou-Rouquette, P. Soulie, C. Perrin, J. Y. Blay, E. Bompas
Summary: This study describes the outcomes, prognostic factors, and treatment of patients with metastatic synovial sarcoma (SS) in a nationwide cohort in France. The results showed that local treatment, management in reference centers, and cytotoxic treatments given in the perioperative and metastatic setting influenced the outcome of patients.
Article
Health Care Sciences & Services
Mathias Neron, Arnaud Guille, Lucie Allegre, Pierre-Emmanuel Colombo, Cristina Leaha, Jose Adelaide, Nadine Carbuccia, Frederic Courtier, Florence Boissiere, Evelyne Crapez, Michel Fabbro, Sebastien Gouy, Emilie Mamessier, Eric Lambaudie, Daniel Birnbaum, Francois Bertucci, Max Chaffanet
Summary: Hormone therapy is an effective and low-toxicity treatment for metastatic endometrial carcinoma. This study focuses on molecular analysis of metastatic endometrial carcinomas treated with hormone therapy, comparing the genomic profiles of primary and metastatic tumors. The objective is to identify predictive factors and altered signaling pathways related to the response to hormone therapy. The findings provide insight into the formation of metastasis and guide the selection of treatment strategies for metastatic endometrial carcinoma.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Oncology
David Jeremie Birnbaum, Maelle Picard, Quentin Da Costa, Thomas Delayre, Pascal Finetti, Olivier Cabaud, Emilie Agavnian, Bernadette De Rauglaudre, Emilie Denicolai, Francois Bertucci, Emilie Mamessier
Summary: Hepatocellular carcinoma (HCC) is a common and deadly cancer, and new treatments are needed. Immune checkpoint inhibitors (ICIs) have shown promise for HCC. By analyzing a large transcriptomic database, we found that the TIGIT/DNAM-1 axis, particularly the PVRIG molecule, could be a potential therapeutic option for HCC.
Article
Oncology
Helene Francois-Martin, Audrey Lardy-Cleaud, Barbara Pistilli, Christelle Levy, Veronique Dieras, Jean-Sebastien Frenel, Severine Guiu, Marie-Ange Mouret-Reynier, Audrey Mailliez, Jean-Christophe Eymard, Thierry Petit, Mony Ung, Isabelle Desmoulins, Paule Augereau, Thomas Bachelot, Lionel Uwer, Marc Debled, Jean-Marc Ferrero, Florian Clatot, Anthony Goncalves, Michael Chevrot, Sylvie Chabaud, Paul Cottu
Summary: This study evaluated the impact of everolimus-based therapy on overall survival in a national cohort of breast cancer patients. The findings suggest that everolimus may improve overall survival in advanced hormone receptor positive, HER2 negative breast cancer, but its usage is currently underutilized in clinical practice.
Article
Oncology
Gilles Houvenaeghel, Monique Cohen, Marc Martino, Fabien Reyal, Jean-Marc Classe, Marie-Pierre Chauvet, Pierre-Emmanuel Colombo, Mellie Heinemann, Eva Jouve, Pierre Gimbergues, Anne-Sophie Azuar, Charles Coutant, Anthony Goncalves, Alexandre de Nonneville
Summary: In this study, the impact of pN0(i+) or pN1mi on the outcomes of HER2-positive breast cancer patients undergoing up-front surgery was investigated. The results showed that pN0(i+) and pN1mi did not adversely affect survival outcomes in HER2-positive patients. However, for pT1a-b HER2-positive breast cancer, a negative impact on recurrence-free survival was observed specifically in patients with pN0(i+) and pN1mi diseases, especially among those with pT1b tumors without adjuvant chemotherapy. These findings emphasize the importance of considering the pN0(i+) and pN1mi status when making decisions about trastuzumab-based adjuvant chemotherapy for these patients.
Article
Oncology
Olivier Tredan, Maud Toulmonde, Christophe Le Tourneau, Laure Montane, Antoine Italiano, Isabelle Ray-Coquard, Christelle de la Fouchardiere, Francois Bertucci, Anthony Goncalves, Carlos Gomez-Roca, Benoit You, Valery Attignon, Sandrine Boyault, Philippe A. Cassier, Armelle Dufresne, Severine Tabone-Eglinger, Alain Viari, Emilie Sohier, Maud Kamal, Gwenael Garin, Jean-Yves Blay, David Perol
Summary: Using a randomized discontinuation design, sorafenib was tested on patients with advanced/metastatic solid tumors harboring sorafenib-targeted genes. Continuing sorafenib when stable disease is achieved improves progression-free rate compared to interruption. Sorafenib has tumor-agnostic efficacy in patients with tumors harboring genomic alterations in PDGFRA/B, VEGF-Rs, Flt-3, KIT, FGFR1 or the RAF/MEK/ERK pathway.
Article
Oncology
Alban Macagno, Alexandre de Nonneville, Pierre Annede, Gilles Piana, Isabelle Pougnet, Nassima Daidj, Laurence Moureau-Zabotto, Julien Darreon, Laetitia Padovani, Francois Bertucci, Naji Salem
Summary: SBRT and TA are alternative treatments for pulmonary oligometastases. This study showed that repeated ablative therapy can be effective in delaying the use of more toxic systemic therapy for patients with pulmonary oligorecurrent metastases.