{
    "nodes": [
        [
            "PIK3CA",
            "GENE"
        ],
        [
            "Trastuzumab",
            "DRUG"
        ],
        [
            "capivasertib",
            "COMPOUND"
        ],
        [
            "NVP-BKM120",
            "COMPOUND"
        ],
        [
            "Paclitaxel",
            "DRUG"
        ],
        [
            "MK 2206",
            "COMPOUND"
        ],
        [
            "4-(2,6-dichlorobenzoyl)-N-methyl-1H-pyrrole-2-carboxamide",
            "COMPOUND"
        ],
        [
            "Fulvestrant",
            "DRUG"
        ],
        [
            "5XGI Crystal structure of PI3K complex with an inhibitor",
            "PDB_STRUCTURE"
        ],
        [
            "Alpelisib",
            "DRUG"
        ],
        [
            "5DTM Crystal structure of Dot1L in complex with inhibitor CPD1 [4-(2,6-dichlorobenzoyl)-N-methyl-1H-pyrrole-2-carboxamide]",
            "PDB_STRUCTURE"
        ]
    ],
    "edges": [
        [
            [
                "PIK3CA",
                "Paclitaxel"
            ],
            7.382791500000001,
            [
                [
                    "Rong Qin, Xiangyang Wang, Tingting Fan, Ting Wu, Chao Lu, Xun Shao, Liang Yin (2024). Bilateral inflammatory recurrence of HER-2 positive breast cancer: a unique case report and literature review. Frontiers in oncology, 1276637. https://doi.org/10.3389/fonc.2024.1276637 PMID: 38283858",
                    "38283858"
                ],
                [
                    "Tomomi Nishimura, Ravi Velaga, Norikazu Masuda, Kosuke Kawaguchi, Shuji Kawaguchi, Masahiro Takada, Yurina Maeshima, Sunao Tanaka, Yuichiro Kikawa, Takayuki Kadoya, Hiroko Bando, Rikiya Nakamura, Yutaka Yamamoto, Takayuki Ueno, Hiroyuki Yasojima, Hiroshi Ishiguro, Satoshi Morita, Shinji Ohno, Hironori Haga, Fumihiko Matsuda, Seishi Ogawa, Masakazu Toi (2024). Genomic and transcriptomic profiling of pre- and postneoadjuvant chemotherapy triple negative breast cancer tumors. Cancer science, 3928-3942. https://doi.org/10.1111/cas.16339 PMID: 39375938",
                    "39375938"
                ],
                [
                    "Hang Lu, Xin Yu, Zhiliang Xu, Jingwen Deng, Master Jingwen Zhang, Yimin Zhang, Shengrong Sun (2024). Prognostic Value of IGFBP6 in Breast Cancer: Focus on Glucometabolism. Technology in cancer research & treatment, 15330338241271998. https://doi.org/10.1177/15330338241271998 PMID: 39275851",
                    "39275851"
                ],
                [
                    "Isis de Araújo Ferreira Muniz, Megan Araujo, Jenna Bouassaly, Fatemeh Farshadi, Mai Atique, Khashayar Esfahani, Paulo Rogerio Ferreti Bonan, Michael Hier, Marco Mascarella, Alex Mlynarek, Moulay Alaoui-Jamali, Sabrina Daniela da Silva (2024). Therapeutic Advances and Challenges for the Management of HPV-Associated Oropharyngeal Cancer. International journal of molecular sciences. https://doi.org/10.3390/ijms25074009 PMID: 38612819",
                    "38612819"
                ],
                [
                    "Robert Roskoski (2024). Targeted and cytotoxic inhibitors used in the treatment of breast cancer. Pharmacological research, 107534. https://doi.org/10.1016/j.phrs.2024.107534 PMID: 39631485",
                    "39631485"
                ],
                [
                    "A Grinshpun, S Ren, N Graham, M K DeMeo, E Wrabel, J Carter, N Tayob, A Pereslete, E Hamilton, D Juric, E L Mayer, S M Tolaney, I E Krop, O Metzger (2024). Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer. ESMO open, 103465. https://doi.org/10.1016/j.esmoop.2024.103465 PMID: 38833970",
                    "38833970"
                ],
                [
                    "Aihua Guo, Peilin Zhong, Linghua Wang, Xiurong Lin, Mei Feng (2024). Prognosis and immunotherapeutic implications of molecular classification of cervical cancer based on immunophenoscore-related genes. Journal of biomolecular structure & dynamics, 1-16. https://doi.org/10.1080/07391102.2024.2404545 PMID: 39308337",
                    "39308337"
                ],
                [
                    "S Pignata, D Califano, D Lorusso, L Arenare, M Bartoletti, U De Giorgi, C Andreetta, C Pisano, G Scambia, D Lombardi, A Farolfi, S Cinieri, A Passarelli, V Salutari, C De Angelis, C Mignogna, D Priolo, E D Capoluongo, S Tamberi, G L Scaglione, V Arcangeli, R De Cecio, G Scognamiglio, F Greco, A Spina, M Turinetto, D Russo, V Carbone, C Casartelli, C Schettino, F Perrone (2024). MITO END-3: efficacy of avelumab immunotherapy according to molecular profiling in first-line endometrial cancer therapy. Annals of oncology : official journal of the European Society for Medical Oncology, 667-676. https://doi.org/10.1016/j.annonc.2024.04.007 PMID: 38704093",
                    "38704093"
                ],
                [
                    "Rebecca A Dent, Sung-Bae Kim, Mafalda Oliveira, Carlos Barrios, Joyce O'Shaughnessy, Steven J Isakoff, Shigehira Saji, Ruffo Freitas-Junior, Manuel Philco, Igor Bondarenko, Qinshu Lian, Denise Bradley, Heather Hinton, Matthew J Wongchenko, Sarah-Jayne Reilly, Nicholas Turner (2024). Ipatasertib plus Paclitaxel for Patients with PIK3CA/AKT1/PTEN-Altered Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer in the IPATunity130 Phase III Trial. Clinical cancer research : an official journal of the American Association for Cancer Research, 4329-4338. https://doi.org/10.1158/1078-0432.CCR-24-0465 PMID: 39058425",
                    "39058425"
                ],
                [
                    "Mohammad Alwahsh, Amani Al-Doridee, Suhair Jasim, Oriana Awwad, Roland Hergenröder, Lama Hamadneh (2024). Cytotoxic and molecular differences of anticancer agents on 2D and 3D cell culture. Molecular biology reports, 721. https://doi.org/10.1007/s11033-024-09669-1 PMID: 38829450",
                    "38829450"
                ]
            ]
        ],
        [
            [
                "5XGI Crystal structure of PI3K complex with an inhibitor",
                "PIK3CA"
            ],
            7.036307399999999
        ],
        [
            [
                "PIK3CA",
                "NVP-BKM120"
            ],
            4.5634285000000006,
            [
                [
                    "Sandeep Kumar, Shalmoli Bhattacharyya, Ashim Das, Gurpreet Singh, Amanjit Bal (2022). In vitro effect of PIK3CA/mTOR inhibition in triple-negative breast cancer subtype cell lines. Breast disease, 241-247. https://doi.org/10.3233/BD-210066 PMID: 35431224",
                    "35431224"
                ],
                [
                    "Yixuan Ma, Sina Sender, Anett Sekora, Weibo Kong, Peter Bauer, Najim Ameziane, Ruslan Al-Ali, Susann Krake, Mandy Radefeldt, Frank Ulrich Weiss, Markus M Lerch, Alisha Parveen, Dietmar Zechner, Christian Junghanss, Hugo Murua Escobar (2022). The Inhibitory Response to PI3K/AKT Pathway Inhibitors MK-2206 and Buparlisib Is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines. International journal of molecular sciences. https://doi.org/10.3390/ijms23084295 PMID: 35457111",
                    "35457111"
                ],
                [
                    "Sun Min Lim, San-Duk Yang, Sangbin Lim, Seong Gu Heo, Stetson Daniel, Aleksandra Markovets, Rafati Minoo, Kyoung-Ho Pyo, Mi Ran Yun, Min Hee Hong, Hye Ryun Kim, Byoung Chul Cho (2022). Molecular landscape of osimertinib resistance in patients and patient-derived preclinical models. Therapeutic advances in medical oncology, 17588359221079125. https://doi.org/10.1177/17588359221079125 PMID: 35251316",
                    "35251316"
                ],
                [
                    "Ge-Ping Qu, Min Shi, Dan Wang, Jiong-He Wu, Peng Wang, Mei-Liang Gong, Zhi-Jian Zhang (2021). Dual targeting of MEK and PI3K effectively controls the proliferation of human EGFR-TKI resistant non-small cell lung carcinoma cell lines with different genetic backgrounds. BMC pulmonary medicine, 208. https://doi.org/10.1186/s12890-021-01571-x PMID: 34210314",
                    "34210314"
                ],
                [
                    "Ariella B Hanker, Benjamin P Brown, Jens Meiler, Arnaldo Marín, Harikrishna S Jayanthan, Dan Ye, Chang-Ching Lin, Hiroaki Akamatsu, Kyung-Min Lee, Sumanta Chatterjee, Dhivya R Sudhan, Alberto Servetto, Monica Red Brewer, James P Koch, Jonathan H Sheehan, Jie He, Alshad S Lalani, Carlos L Arteaga (2021). Co-occurring gain-of-function mutations in HER2 and HER3 modulate HER2/HER3 activation, oncogenesis, and HER2 inhibitor sensitivity. Cancer cell, 1099-1114.e8. https://doi.org/10.1016/j.ccell.2021.06.001 PMID: 34171264",
                    "34171264"
                ],
                [
                    "Jinshan Xing, Jun Yang, Yingjiang Gu, Jingyan Yi (2021). Research update on the anticancer effects of buparlisib. Oncology letters, 266. https://doi.org/10.3892/ol.2021.12527 PMID: 33717263",
                    "33717263"
                ],
                [
                    "Chi-Heng Wu, Chen-Yen Yang, Linlin Wang, Hua-Xin Gao, Taha Rakhshandehroo, Shervin Afghani, Laura Pincus, Ronald Balassanian, James Rubenstein, Ryan Gill, Sourav Bandyopadhyay, Frank McCormick, Mark Moasser, Weiyun Z Ai (2021). Cutaneous T-Cell Lymphoma PDX Drug Screening Platform Identifies Cooperation between Inhibitions of PI3Kα/δ and HDAC. The Journal of investigative dermatology, 364-373. https://doi.org/10.1016/j.jid.2020.05.110 PMID: 32603749",
                    "32603749"
                ],
                [
                    "Cristina Uribe-Alvarez, Sandra Lucía Guerrero-Rodríguez, Jennifer Rhodes, Alexa Cannon, Jonathan Chernoff, Daniela Araiza-Olivera (2021). Targeting effector pathways in RAC1P29S-driven malignant melanoma. Small GTPases, 273-281. https://doi.org/10.1080/21541248.2020.1728469 PMID: 32043900",
                    "32043900"
                ],
                [
                    "Tong Zhao, Yuqin Tian, Xinjia Ding, Lin Liu, Bowen Tan, Bin Yang, Jianlin Wu, Ting Lei, Ruoyu Wang, Yan Ding (2021). Genetic Analysis and Targeted Therapy Using Buparlisib and MK2206 in a Patient with Triple Metachronous Cancers of the Kidney, Prostate, and Squamous Cell Carcinoma of the Lung: A Case Report. OncoTargets and therapy, 2839-2845. https://doi.org/10.2147/OTT.S298697 PMID: 33953569",
                    "33953569"
                ],
                [
                    "Dwan-Ying Chang, Wei-Li Ma, Yen-Shen Lu (2021). Role of Alpelisib in the Treatment of PIK3CA-Mutated Breast Cancer: Patient Selection and Clinical Perspectives. Therapeutics and clinical risk management, 193-207. https://doi.org/10.2147/TCRM.S251668 PMID: 33707948",
                    "33707948"
                ]
            ]
        ],
        [
            [
                "PIK3CA",
                "capivasertib"
            ],
            4.021084,
            [
                [
                    "Adrish Sen, Salmaan Khan, Stefano Rossetti, Aaron Broege, Ian MacNeil, Ann DeLaForest, Jhomary Molden, Laura Davis, Charles Iversrud, Megan Seibel, Ross Kopher, Stephen Schulz, Lance Laing (2025). Assessments of prostate cancer cell functions highlight differences between a pan-PI3K/mTOR inhibitor, gedatolisib, and single-node inhibitors of the PI3K/AKT/mTOR pathway. Molecular oncology, 225-247. https://doi.org/10.1002/1878-0261.13703 PMID: 39092562",
                    "39092562"
                ],
                [
                    "Matt Shirley (2024). Capivasertib: First Approval. Drugs, 337-346. https://doi.org/10.1007/s40265-024-01998-6 PMID: 38388873",
                    "38388873"
                ],
                [
                    "Constance A Sobsey, Bjoern C Froehlich, Georgia Mitsa, Sahar Ibrahim, Robert Popp, Rene P Zahedi, Elza C de Bruin, Christoph H Borchers, Gerald Batist (2024). mTORC1-Driven Protein Translation Correlates with Clinical Benefit of Capivasertib within a Genetically Preselected Cohort of PIK3CA-Altered Tumors. Cancer research communications, 2058-2074. https://doi.org/10.1158/2767-9764.CRC-24-0113 PMID: 38954770",
                    "38954770"
                ],
                [
                    "Mafalda Oliveira, Hope S Rugo, Sacha J Howell, Florence Dalenc, Javier Cortes, Henry L Gomez, Xichun Hu, Masakazu Toi, Komal Jhaveri, Petr Krivorotko, Sibylle Loibl, Serafin Morales Murillo, Meena Okera, Zbigniew Nowecki, Yeon Hee Park, Joo Hyuk Sohn, Eriko Tokunaga, Samih Yousef, Lyudmila Zhukova, Marta Fulford, Haylee Andrews, Ian Wadsworth, Celina D'Cruz, Nicholas C Turner,   (2024). Capivasertib and fulvestrant for patients with hormone receptor-positive, HER2-negative advanced breast cancer (CAPItello-291): patient-reported outcomes from a phase 3, randomised, double-blind, placebo-controlled trial. The Lancet. Oncology, 1231-1244. https://doi.org/10.1016/S1470-2045(24)00373-5 PMID: 39214106",
                    "39214106"
                ],
                [
                    "Iseult M Browne, Alicia F C Okines (2024). Resistance to Targeted Inhibitors of the PI3K/AKT/mTOR Pathway in Advanced Oestrogen-Receptor-Positive Breast Cancer. Cancers. https://doi.org/10.3390/cancers16122259 PMID: 38927964",
                    "38927964"
                ],
                [
                    "K Fanucci, A Giordano, T Erick, S M Tolaney, S Sammons (2024). Practical treatment strategies and novel therapies in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) advanced breast cancer. ESMO open, 103997. https://doi.org/10.1016/j.esmoop.2024.103997 PMID: 39674130",
                    "39674130"
                ],
                [
                    "Victor Heurtier, Alexandre de Nonneville (2024). [Capivasertib in combination with fulvestrant in locally advanced or metastatic RH+ HER2- breast cancer with PIK3CA, AKT1 or PTEN alteration, after first-line hormonal therapy]. Bulletin du cancer, 997-998. https://doi.org/10.1016/j.bulcan.2024.08.010 PMID: 39317592",
                    "39317592"
                ],
                [
                    "M Sirico, F Jacobs, C Molinelli, Guilherme Nader-Marta, V Debien, H Faith Dewhurst, M Palleschi, F Merloni, C Gianni, U De Giorgi, Evandro de Azambuja (2024). Navigating the complexity of PI3K/AKT pathway in HER-2 negative breast cancer: biomarkers and beyond. Critical reviews in oncology/hematology, 104404. https://doi.org/10.1016/j.critrevonc.2024.104404 PMID: 38815877",
                    "38815877"
                ],
                [
                    "Ursula Grazini, Aleksandra Markovets, Lucy Ireland, Daniel O'Neill, Benjamin Phillips, Man Xu, Matthias Pfeifer, Tereza Vaclova, Matthew J Martin, Ludovic Bigot, Luc Friboulet, Ryan Hartmaier, Maria E Cuomo, Simon T Barry, Paul D Smith, Nicolas Floc'h (2024). Overcoming Osimertinib Resistance with AKT Inhibition in EGFRm-Driven Non-Small Cell Lung Cancer with PIK3CA/PTEN Alterations. Clinical cancer research : an official journal of the American Association for Cancer Research, 4143-4154. https://doi.org/10.1158/1078-0432.CCR-23-2540 PMID: 38630555",
                    "38630555"
                ],
                [
                    "Midori Morita, Ryo Tsunashima, Tetsuhiro Yoshinami, Masaki Ishida, Masahiro Iwasaku, Sae Kitano, Chikage Kato, Koichi Sakaguchi, Koichi Takayama, Yasuto Naoi (2024). A 5-year review of genomic medicine in breast cancer: insights from C-CAT data on 3776 Japanese patients. Breast cancer (Tokyo, Japan). https://doi.org/10.1007/s12282-024-01656-5 PMID: 39630210",
                    "39630210"
                ]
            ]
        ],
        [
            [
                "PIK3CA",
                "Trastuzumab"
            ],
            6.5044113,
            [
                [
                    "Rong Qin, Xiangyang Wang, Tingting Fan, Ting Wu, Chao Lu, Xun Shao, Liang Yin (2024). Bilateral inflammatory recurrence of HER-2 positive breast cancer: a unique case report and literature review. Frontiers in oncology, 1276637. https://doi.org/10.3389/fonc.2024.1276637 PMID: 38283858",
                    "38283858"
                ],
                [
                    "Asmaa Mohamed Mekhamer, Marwa Hanafi Saied, Dalia Abd Elmoaty Elneily, Tarek Abdel Halim El-Fayoumi, Doaa Ibrahim Hashad (2024). Targeted Sequencing of HER2-Positive Breast Cancer Mutations Revealed a Potential Association between PIK3CA and Trastuzumab Resistance. Asian Pacific journal of cancer prevention : APJCP, 4051-4059. https://doi.org/10.31557/APJCP.2024.25.11.4051 PMID: 39611930",
                    "39611930"
                ],
                [
                    "Diana-Theodora Morgos, Constantin Stefani, Daniela Miricescu, Maria Greabu, Silviu Stanciu, Silvia Nica, Iulia-Ioana Stanescu-Spinu, Daniela Gabriela Balan, Andra-Elena Balcangiu-Stroescu, Elena-Claudia Coculescu, Dragos-Eugen Georgescu, Remus Iulian Nica (2024). Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer. International journal of molecular sciences. https://doi.org/10.3390/ijms25031848 PMID: 38339127",
                    "38339127"
                ],
                [
                    "Salvatore Siena, Kanwal Raghav, Toshiki Masuishi, Kensei Yamaguchi, Tomohiro Nishina, Elena Elez, Javier Rodriguez, Ian Chau, Maria Di Bartolomeo, Hisato Kawakami, Fumitaka Suto, Makito Koga, Koichiro Inaki, Yusuke Kuwahara, Issey Takehara, Daniel Barrios, Kojiro Kobayashi, Axel Grothey, Takayuki Yoshino (2024). HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01. Nature communications, 10213. https://doi.org/10.1038/s41467-024-53223-3 PMID: 39587050",
                    "39587050"
                ],
                [
                    "Shaimaa Abdel-Ghany, Yasmin Khalid, Soha Mohamed, Gehan Mohamed, Engy Mohdy, Abeer Ezzat, Engy F Madian, Osama A Said, Mohamed A Abdel-Hakeem, Mahmoud Nazih, Ahmed Khoder, Hussein Sabit (2024). Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing Potential. Breast cancer : basic and clinical research, 11782234241285411. https://doi.org/10.1177/11782234241285411 PMID: 39611037",
                    "39611037"
                ],
                [
                    "Qiyun Shi, Juncheng Xuhong, Tao Luo, Jia Ge, Feng Liu, Yang Lan, Qingqiu Chen, Peng Tang, Linjun Fan, Li Chen, Yan Liang, Minghao Wang, Ying Hu, Yi Zhang, Xiuwu Bian, Xiaowei Qi, Jun Jiang (2023). PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer. British journal of cancer, 121-129. https://doi.org/10.1038/s41416-022-02021-z PMID: 36323880",
                    "36323880"
                ],
                [
                    "Karine Ronan, Emmet Jordan, Christine Leonard, Ray McDermott (2023). Frequency of next-generation sequencing, prevalence of targetable mutations and response to targeted therapies amongst patients with metastatic urothelial cancer in Ireland: a multi-centre retrospective study of real-world data. Irish journal of medical science. https://doi.org/10.1007/s11845-023-03569-2 PMID: 37947995",
                    "37947995"
                ],
                [
                    "Apolonia Novillo, María Gaibar, Alicia Romero-Lorca, Diego Malón, Beatriz Antón, Amalia Moreno, Ana Fernández-Santander (2023). HER2 and BARD1 Polymorphisms in Early HER2-Positive Breast Cancer Patients: Relationship with Response to Neoadjuvant Anti-HER2 Treatment. Cancers. https://doi.org/10.3390/cancers15030763 PMID: 36765720",
                    "36765720"
                ],
                [
                    "Marla Lipsyc-Sharf, Esha Jain, Laura C Collins, Shoshana M Rosenberg, Kathryn J Ruddy, Rulla M Tamimi, Lidia Schapira, Steven E Come, Jeffrey M Peppercorn, Virginia F Borges, Ellen Warner, Craig Snow, Ian E Krop, Dewey Kim, Jakob Weiss, Jorge Gomez Tejeda Zanudo, Ann H Partridge, Nikhil Wagle, Adrienne G Waks (2023). Genomics of ERBB2-Positive Breast Cancer in Young Women Before and After Exposure to Chemotherapy Plus Trastuzumab. JCO precision oncology, e2300076. https://doi.org/10.1200/PO.23.00076 PMID: 37364233",
                    "37364233"
                ],
                [
                    "Paola Zagami, Aranzazu Fernandez-Martinez, Naim U Rashid, Katherine A Hoadley, Patricia A Spears, Giuseppe Curigliano, Charles M Perou, Lisa A Carey (2023). Association of PIK3CA Mutation With Pathologic Complete Response and Outcome by Hormone Receptor Status and Intrinsic Subtype in Early-Stage ERBB2/HER2-Positive Breast Cancer. JAMA network open, e2348814. https://doi.org/10.1001/jamanetworkopen.2023.48814 PMID: 38117494",
                    "38117494"
                ]
            ]
        ],
        [
            [
                "PIK3CA",
                "Fulvestrant"
            ],
            15.312574000000001,
            [
                [
                    "Adrish Sen, Salmaan Khan, Stefano Rossetti, Aaron Broege, Ian MacNeil, Ann DeLaForest, Jhomary Molden, Laura Davis, Charles Iversrud, Megan Seibel, Ross Kopher, Stephen Schulz, Lance Laing (2025). Assessments of prostate cancer cell functions highlight differences between a pan-PI3K/mTOR inhibitor, gedatolisib, and single-node inhibitors of the PI3K/AKT/mTOR pathway. Molecular oncology, 225-247. https://doi.org/10.1002/1878-0261.13703 PMID: 39092562",
                    "39092562"
                ],
                [
                    "Victor Heurtier, Alexandre de Nonneville (2024). [Capivasertib in combination with fulvestrant in locally advanced or metastatic RH+ HER2- breast cancer with PIK3CA, AKT1 or PTEN alteration, after first-line hormonal therapy]. Bulletin du cancer, 997-998. https://doi.org/10.1016/j.bulcan.2024.08.010 PMID: 39317592",
                    "39317592"
                ],
                [
                    "Eriko Tokunaga, Hiroji Iwata, Mitsuya Itoh, Tetsuhiko Taira, Tatsuya Toyama, Toshiro Mizuno, Akihiko Osaki, Yasuhiro Yanagita, Seigo Nakamura, Rikiya Nakamura, Tomoko Sambe, Toshiaki Ozaki, Gaia Schiavon, Sacha J Howell, Masakazu Toi (2024). Capivasertib and fulvestrant for patients with HR-positive/HER2-negative advanced breast cancer: analysis of the subgroup of patients from Japan in the phase 3 CAPItello-291 trial. Breast cancer (Tokyo, Japan). https://doi.org/10.1007/s12282-024-01640-z PMID: 39379782",
                    "39379782"
                ],
                [
                    "Robert Roskoski (2024). Targeted and cytotoxic inhibitors used in the treatment of breast cancer. Pharmacological research, 107534. https://doi.org/10.1016/j.phrs.2024.107534 PMID: 39631485",
                    "39631485"
                ],
                [
                    "Asma Dilawari, James Buturla, Christy Osgood, Xin Gao, Wei Chen, Tiffany K Ricks, Timothy Schaefer, Sreedevi Avasarala, Francisca Reyes Turcu, Anand Pathak, Shyam Kalavar, Vishal Bhatnagar, Justin Collazo, Nam Atiqur Rahman, Bronwyn Mixter, Shenghui Tang, Richard Pazdur, Paul Kluetz, Laleh Amiri-Kordestani (2024). US Food and Drug Administration Approval Summary: Capivasertib With Fulvestrant for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer With PIK3CA/AKT1/PTEN Alterations. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 4103-4113. https://doi.org/10.1200/JCO.24.00427 PMID: 39159418",
                    "39159418"
                ],
                [
                    "Li Zhang, Yanlei Zheng, Gao Chen, Fang Zhao, Shi Li (2024). Case report: Phosphoinositide 3-kinase inhibitor with fulvestrant in a patient with ER+/HER2- metastatic breast carcinoma induced fatal arrhythmias: a preventable event? Frontiers in oncology, 1331472. https://doi.org/10.3389/fonc.2024.1331472 PMID: 38952547",
                    "38952547"
                ],
                [
                    "Nicholas C Turner, Mafalda Oliveira, Sacha J Howell, Florence Dalenc, Javier Cortés, Henry L Gomez, Xichun Hu, Komal Jhaveri, Petr Krivorotko, Sibylle Loibl, Serafin Morales Murillo, Yeon Hee Park, Joo-Hyuk Sohn, Masakazu Toi, Eriko Tokunaga, Samih Yousef, Lyudmila Zhukova, Elza de Bruin, Lynda Grinsted, Gaia Schiavon, Andrew Foxley, Hope S Rugo (2024). A plain language summary of the CAPItello-291 study: Capivasertib in hormone receptor-positive advanced breast cancer. Future oncology (London, England), 2901-2913. https://doi.org/10.1080/14796694.2024.2390791 PMID: 39283299",
                    "39283299"
                ],
                [
                    "Constance A Sobsey, Bjoern C Froehlich, Georgia Mitsa, Sahar Ibrahim, Robert Popp, Rene P Zahedi, Elza C de Bruin, Christoph H Borchers, Gerald Batist (2024). mTORC1-Driven Protein Translation Correlates with Clinical Benefit of Capivasertib within a Genetically Preselected Cohort of PIK3CA-Altered Tumors. Cancer research communications, 2058-2074. https://doi.org/10.1158/2767-9764.CRC-24-0113 PMID: 38954770",
                    "38954770"
                ],
                [
                    "Kevin Kalinsky, Giampaolo Bianchini, Erika Hamilton, Stephanie L Graff, Kyong Hwa Park, Rinath Jeselsohn, Umut Demirci, Miguel Martin, Rachel M Layman, Sara A Hurvitz, Sarah Sammons, Peter A Kaufman, Montserrat Muñoz, Jiun-I Lai, Holly Knoderer, Cynthia Sandoval, Aarti R Chawla, Bastien Nguyen, Yanhong Zhou, Elizabeth Ravenberg, Lacey M Litchfield, Lillian Smyth, Seth A Wander (2024). Abemaciclib Plus Fulvestrant in Advanced Breast Cancer Following Progression on CDK4/6 Inhibition: Results from the Phase III postMONARCH Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, JCO2402086. https://doi.org/10.1200/JCO-24-02086 PMID: 39693591",
                    "39693591"
                ],
                [
                    "Mafalda Oliveira, Hope S Rugo, Sacha J Howell, Florence Dalenc, Javier Cortes, Henry L Gomez, Xichun Hu, Masakazu Toi, Komal Jhaveri, Petr Krivorotko, Sibylle Loibl, Serafin Morales Murillo, Meena Okera, Zbigniew Nowecki, Yeon Hee Park, Joo Hyuk Sohn, Eriko Tokunaga, Samih Yousef, Lyudmila Zhukova, Marta Fulford, Haylee Andrews, Ian Wadsworth, Celina D'Cruz, Nicholas C Turner,   (2024). Capivasertib and fulvestrant for patients with hormone receptor-positive, HER2-negative advanced breast cancer (CAPItello-291): patient-reported outcomes from a phase 3, randomised, double-blind, placebo-controlled trial. The Lancet. Oncology, 1231-1244. https://doi.org/10.1016/S1470-2045(24)00373-5 PMID: 39214106",
                    "39214106"
                ]
            ]
        ],
        [
            [
                "PIK3CA",
                "MK 2206"
            ],
            3.343206,
            [
                [
                    "Daniel J Smit, Helena Brauer, Stefan Horn, Gökhan Yigit, Marie-Therese Haider, Vivian Pogenberg, Udo Schumacher, Klaus Pantel, Manfred Jücker (2024). Functional characterization of PI3K C2 domain mutations detected in breast cancer circulating tumor cells and metastatic cells. Cellular signalling, 111270. https://doi.org/10.1016/j.cellsig.2024.111270 PMID: 38909932",
                    "38909932"
                ],
                [
                    "Yixuan Ma, Sina Sender, Anett Sekora, Weibo Kong, Peter Bauer, Najim Ameziane, Ruslan Al-Ali, Susann Krake, Mandy Radefeldt, Frank Ulrich Weiss, Markus M Lerch, Alisha Parveen, Dietmar Zechner, Christian Junghanss, Hugo Murua Escobar (2022). The Inhibitory Response to PI3K/AKT Pathway Inhibitors MK-2206 and Buparlisib Is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines. International journal of molecular sciences. https://doi.org/10.3390/ijms23084295 PMID: 35457111",
                    "35457111"
                ],
                [
                    "Supharada Tessiri, Anchalee Techasen, Sarinya Kongpetch, Achira Namjan, Watcharin Loilome, Waraporn Chan-On, Raynoo Thanan, Apinya Jusakul (2022). Therapeutic targeting of ARID1A and PI3K/AKT pathway alterations in cholangiocarcinoma. PeerJ, e12750. https://doi.org/10.7717/peerj.12750 PMID: 35070505",
                    "35070505"
                ],
                [
                    "Shuhang Liang, Hongrui Guo, Kun Ma, Xianying Li, Dehai Wu, Yiqi Wang, Wei Wang, Shugeng Zhang, Yifeng Cui, Yufeng Liu, Linmao Sun, Bo Zhang, Mengyang Xin, Ning Zhang, Huanran Zhou, Yao Liu, Jiabei Wang, Lianxin Liu (2021). A PLCB1-PI3K-AKT Signaling Axis Activates EMT to Promote Cholangiocarcinoma Progression. Cancer research, 5889-5903. https://doi.org/10.1158/0008-5472.CAN-21-1538 PMID: 34580062",
                    "34580062"
                ],
                [
                    "Tong Zhao, Yuqin Tian, Xinjia Ding, Lin Liu, Bowen Tan, Bin Yang, Jianlin Wu, Ting Lei, Ruoyu Wang, Yan Ding (2021). Genetic Analysis and Targeted Therapy Using Buparlisib and MK2206 in a Patient with Triple Metachronous Cancers of the Kidney, Prostate, and Squamous Cell Carcinoma of the Lung: A Case Report. OncoTargets and therapy, 2839-2845. https://doi.org/10.2147/OTT.S298697 PMID: 33953569",
                    "33953569"
                ],
                [
                    "Ruyue Xu, Yinci Zhang, Amin Li, Yongfang Ma, Wenpeng Cai, Li Song, Yinghai Xie, Shuping Zhou, Weiya Cao, Xiaolong Tang (2021). LY‑294002 enhances the chemosensitivity of liver cancer to oxaliplatin by blocking the PI3K/AKT/HIF‑1α pathway. Molecular medicine reports. PMID: 33982772",
                    "33982772"
                ],
                [
                    "Jeremy Johnson, Zeta Chow, Dana Napier, Eun Lee, Heidi L Weiss, B Mark Evers, Piotr Rychahou (2020). Targeting PI3K and AMPKα Signaling Alone or in Combination to Enhance Radiosensitivity of Triple Negative Breast Cancer. Cells. https://doi.org/10.3390/cells9051253 PMID: 32438621",
                    "32438621"
                ],
                [
                    "Andrea P Myers, Panagiotis A Konstantinopoulos, William T Barry, Weixiu Luo, Russell R Broaddus, Vicky Makker, Ronny Drapkin, Joyce Liu, Austin Doyle, Neil S Horowitz, Funda Meric-Bernstam, Michael Birrer, Carol Aghajanian, Robert L Coleman, Gordon B Mills, Lewis C Cantley, Ursula A Matulonis, Shannon N Westin (2020). Phase II, 2-stage, 2-arm, PIK3CA mutation stratified trial of MK-2206 in recurrent endometrial cancer. International journal of cancer, 413-422. https://doi.org/10.1002/ijc.32783 PMID: 31714586",
                    "31714586"
                ],
                [
                    "Yan Xing, Nancy U Lin, Matthew A Maurer, Huiqin Chen, Armeen Mahvash, Aysegul Sahin, Argun Akcakanat, Yisheng Li, Vandana Abramson, Jennifer Litton, Mariana Chavez-MacGregor, Vicente Valero, Sarina A Piha-Paul, David Hong, Kim-Anh Do, Emily Tarco, Dianna Riall, Agda Karina Eterovic, Gerburg M Wulf, Lewis C Cantley, Gordon B Mills, L Austin Doyle, Eric Winer, Gabriel N Hortobagyi, Ana Maria Gonzalez-Angulo, Funda Meric-Bernstam (2019). Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation. Breast cancer research : BCR, 78. https://doi.org/10.1186/s13058-019-1154-8 PMID: 31277699",
                    "31277699"
                ],
                [
                    "Katy Teo, Laura Gómez-Cuadrado, Milou Tenhagen, Adam Byron, Max Rätze, Miranda van Amersfoort, Jojanneke Renes, Eric Strengman, Amit Mandoli, Abhishek A Singh, Joost H Martens, Hendrik G Stunnenberg, Paul J van Diest, Valerie G Brunton, Patrick W B Derksen (2018). E-cadherin loss induces targetable autocrine activation of growth factor signalling in lobular breast cancer. Scientific reports, 15454. https://doi.org/10.1038/s41598-018-33525-5 PMID: 30337563",
                    "30337563"
                ]
            ]
        ],
        [
            [
                "PIK3CA",
                "Alpelisib"
            ],
            16.200688,
            [
                [
                    "Baoyu He, Qingli Bie, Rou Zhao, Yugang Yan, Guanjun Dong, Baogui Zhang, Sen Wang, Wenrong Xu, Dongxing Tian, Yujun Hao, Yanhua Zhang, Mingsheng Zhao, Huabao Xiong, Bin Zhang (2024). Arachidonic acid released by PIK3CA mutant tumor cells triggers malignant transformation of colonic epithelium by inducing chromatin remodeling. Cell reports. Medicine, 101510. https://doi.org/10.1016/j.xcrm.2024.101510 PMID: 38614093",
                    "38614093"
                ],
                [
                    "Iseult M Browne, Alicia F C Okines (2024). Resistance to Targeted Inhibitors of the PI3K/AKT/mTOR Pathway in Advanced Oestrogen-Receptor-Positive Breast Cancer. Cancers. https://doi.org/10.3390/cancers16122259 PMID: 38927964",
                    "38927964"
                ],
                [
                    "Tomás Reinert, Fernanda Orpinelli do Rego, Matheus Costa E Silva, Amanda Muniz Rodrigues, Fernanda Christtanini Koyama, Aline Coelho Gonçalves, Maiane Maria Pauletto, Leandro Jonata de Carvalho Oliveira, Cristiano Augusto Andrade de Resende, Luciana Castro Garcia Landeiro, Carlos Henrique Barrios, Max Senna Mano, Rodrigo Dienstmann (2024). The somatic mutation profile of estrogen receptor-positive HER2-negative metastatic breast cancer in Brazilian patients. Frontiers in oncology, 1372947. https://doi.org/10.3389/fonc.2024.1372947 PMID: 38952553",
                    "38952553"
                ],
                [
                    "Benjamin Edmonds, Jacqueline P Ngo, Aran Groves, Beck Reyes, Rolanda A Gott, Dennis J Chia, Hilda Mirbaha, Shino Magaki, Negar Khanlou, Stacy L Pineles, Noriko Salamon, Rachel M Thompson, Maya Newman, Rajsekar R Rajaraman, Shaun A Hussain, Aria Fallah, Bianca Russell, Hiroki Nariai (2024). Multi-disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series. Epilepsia open, 2510-2517. https://doi.org/10.1002/epi4.13079 PMID: 39442533",
                    "39442533"
                ],
                [
                    "Lukas Bissegger, Theodora A Constantin, Erhan Keles, Luka Raguž, Isobel Barlow-Busch, Clara Orbegozo, Thorsten Schaefer, Valentina Borlandelli, Thomas Bohnacker, Rohitha Sriramaratnam, Alexander Schäfer, Matthias Gstaiger, John E Burke, Chiara Borsari, Matthias P Wymann (2024). Rapid, potent, and persistent covalent chemical probes to deconvolute PI3Kα signaling. Chemical science, 20274-20291. https://doi.org/10.1039/d4sc05459h PMID: 39568927",
                    "39568927"
                ],
                [
                    "Muhammad Shafiq, Zaid Anis Sherwani, Mamona Mushtaq, Mohammad Nur-E-Alam, Aftab Ahmad, Zaheer Ul-Haq (2024). A deep learning-based theoretical protocol to identify potentially isoform-selective PI3Kα inhibitors. Molecular diversity, 1907-1924. https://doi.org/10.1007/s11030-023-10799-0 PMID: 38305819",
                    "38305819"
                ],
                [
                    "Hon Yan Kelvin Yip, Sung-Young Shin, Annabel Chee, Ching-Seng Ang, Fernando J Rossello, Lee Hwa Wong, Lan K Nguyen, Antonella Papa (2024). Integrative modeling uncovers p21-driven drug resistance and prioritizes therapies for PIK3CA-mutant breast cancer. NPJ precision oncology, 20. https://doi.org/10.1038/s41698-024-00496-y PMID: 38273040",
                    "38273040"
                ],
                [
                    "Junna Yamaguchi, Pierre Isnard, Noémie Robil, Pierre de la Grange, Clément Hoguin, Alain Schmitt, Aurélie Hummel, Jérôme Megret, Nicolas Goudin, Marine Luka, Mickaël M Ménager, Cécile Masson, Mohammed Zarhrate, Christine Bôle-Feysot, Michalina Janiszewska, Kornelia Polyak, Julien Dairou, Sara Baldassari, Stéphanie Baulac, Christine Broissand, Christophe Legendre, Fabiola Terzi, Guillaume Canaud (2024). PIK3CA inhibition in models of proliferative glomerulonephritis and lupus nephritis. The Journal of clinical investigation. PMID: 38842935",
                    "38842935"
                ],
                [
                    "Samar I Faggal, Yara El-Dash, Amr Sonousi, Amr M Abdou, Rasha A Hassan (2024). Design, synthesis, and biological evaluation of novel thiazole derivatives as PI3K/mTOR dual inhibitors. RSC medicinal chemistry. https://doi.org/10.1039/d4md00462k PMID: 39345714",
                    "39345714"
                ],
                [
                    "Amy T Ku, Adelaide I J Young, Ahmed Atef Ibrahim, Wen Bu, Weiyu Jiang, Meng Lin, Laterrica C Williams, Bryant Lee McCue, George Miles, Chandandeep Nagi, Fariba Behbod, Yi Li (2023). Short-term PI3K Inhibition Prevents Breast Cancer in Preclinical Models. Cancer prevention research (Philadelphia, Pa.), 65-73. https://doi.org/10.1158/1940-6207.CAPR-22-0275 PMID: 36343340",
                    "36343340"
                ]
            ]
        ],
        [
            [
                "5DTM Crystal structure of Dot1L in complex with inhibitor CPD1 [4-(2,6-dichlorobenzoyl)-N-methyl-1H-pyrrole-2-carboxamide]",
                "4-(2,6-dichlorobenzoyl)-N-methyl-1H-pyrrole-2-carboxamide"
            ],
            7.036307399999999
        ]
    ]
}