Review
Biochemistry & Molecular Biology
Victor Albarran, Diana Isabel Rosero, Jesus Chamorro, Javier Pozas, Maria San Roman, Ana Maria Barrill, Victor Alia, Pilar Sotoca, Patricia Guerrero, Juan Carlos Calvo, Inmaculada Orejana, Patricia Perez de Aguado, Pablo Gajate
Summary: Metastatic urothelial cancer is a major cause of cancer-related death, but new treatment approaches targeting Her-2 show promise, especially with the emergence of antibody-drug conjugates as a novel therapy for advanced cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Hui Hua, Jiajia Zeng, Haixin Xing, Yuxin He, Linyu Han, Nasha Zhang, Ming Yang
Summary: This study systematically evaluated the role of genetic variants in A-to-I editing genes on the prognosis of NSCLC patients receiving EGFR-TKIs therapy. The researchers identified several SNPs in the ADAR gene that were significantly associated with patient prognosis and found that silencing ADAR enhanced the sensitivity of NSCLC cells to gefitinib. These findings highlight the importance of A-to-I RNA editing in drug resistance and suggest ADAR as a potential therapeutic target for unresectable NSCLC.
Article
Medicine, Research & Experimental
Dan Yan, Justus M. Huelse, Dmitri Kireev, Zikang Tan, Luxiao Chen, Subir Goyal, Xiaodong Wang, Stephen Frye, Madhusmita Behera, Frank Schneider, Suresh S. Ramalingam, Taofeek Owonikoko, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Summary: Acquired resistance is inevitable in non-small cell lung cancers (NSCLCs) treated with osimertinib (OSI). Activation of MERTK is associated with OSI resistance and inhibition of MERTK kinase can resensitize resistant cells to OSI.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Jung Hee Cho, Yeon-Mi You, Han Koo, Dong Chul Lee, Young Il Yeom, Kyung Chan Park
Summary: This study identified LPIN1 as a key factor in regulating gefitinib resistance in EGFR-mutant NSCLC cells, and found that LPIN1 expression was induced following gefitinib treatment, leading to increased lipid droplet formation and activation of protein kinase C delta and nuclear factor kappa B. Targeting LPIN1 was shown to synergistically inhibit tumor growth, suggesting a potential effective strategy for preventing TKI resistance in NSCLC patients.
Article
Multidisciplinary Sciences
Xin Yu Koh, Xiao Hui Koh, Diana Spiegelberg, Preeti Jha, Marika Nestor, Le-ann Hwang, Ban Xiong Tan, David Philip Lane
Summary: The RON receptor tyrosine kinase is a promising target for oncology and immunology. The development of potent and selective anti-RON antibodies with high affinity binding has the potential to inhibit tumor growth and enhance tumor immune rejection. These antibodies can also be used for immuno-positron emission tomography imaging and recognize universally exposed RON epitopes on the cell surface.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Pasi A. Janne, Christina Baik, Wu-Chou Su, Melissa L. Johnson, Hidetoshi Hayashi, Makoto Nishio, Dong-Wan Kim, Marianna Koczywas, Kathryn A. Gold, Conor E. Steuer, Haruyasu Murakami, James Chih-Hsin Yang, Sang-We Kim, Michele Vigliotti, Rong Shi, Zhenhao Qi, Yang Qiu, Lihui Zhao, David Sternberg, Channing Yu, Helena A. Yu
Summary: HER3-DXd shows clinical activity in EGFR TKI-resistant lung cancer, regardless of resistance mechanisms, providing a new approach to treat drug-resistant cancers.
Article
Cell Biology
Pinar Ozden Eser, Raymond M. Paranal, Jieun Son, Elena Ivanova, Yanan Kuang, Heidi M. Haikala, Ciric To, Jeffrey J. Okoro, Kshiti H. Dholakia, Jihyun Choi, Yoonji Eum, Atsuko Ogino, Pavlos Missios, Dalia Ercan, Man Xu, Michael J. Poitras, Stephen Wang, Kenneth Ngo, Michael Dills, Masahiko Yanagita, Timothy Lopez, Mika Lin, Jeanelle Tsai, Nicolas Floch, Emily S. Chambers, Jennifer Heng, Rana Anjum, Alison D. Santucci, Kesi Michael, Alwin G. Schuller, Darren Cross, Paul D. Smith, Geoffrey R. Oxnard, David A. Barbie, Lynette M. Sholl, Magda Bahcall, Sangeetha Palakurthi, Prafulla C. Gokhale, Cloud P. Paweletz, George Q. Daley, Pasi A. Janne
Summary: Some EGFR-mutant, MET-amplified lung cancers may develop dependence on MET activation alone, suggesting that these patients could be treated with a single-agent MET TKI instead of the current standard-of-care EGFR and MET inhibitor combination regimens.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Xinyuan Xi, Fan Lei, Keliang Gao, Jingjing Li, Rihe Liu, Adam R. Karpf, Tatiana K. Bronich
Summary: Combining chemotherapeutic drugs in a single nanocarrier offers advantages in cancer treatment, including reducing toxicity, improving drug properties, and enhancing therapeutic effects. In this study, we developed functional multimodal polypeptide-based polymeric nanogels (NGs) to encapsulate a combination of drugs. These NGs exhibited selective cytotoxicity towards EGFR overexpressing ovarian cancer cells and showed preferential associations with EGFR (+) tumor cells. Furthermore, ligand-installed NGs carrying the drug combination significantly improved the treatment response of ovarian cancer xenografts compared to individual drug-loaded NGs. This work highlights the potential of our carrier system for efficient delivery of drug combinations to treat EGFR overexpressing cancers.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Oncology
Ashish Noronha, Nishanth Belugali Nataraj, Joo Sang Lee, Benny Zhitomirsky, Yaara Oren, Sara Oster, Moshit Lindzen, Saptaparna Mukherjee, Rainer Will, Soma Ghosh, Arturo Simoni-Nieves, Aakanksha Verma, Rishita Chatterjee, Simone Borgoni, Welles Robinson, Sanju Sinha, Alexander Brandis, D. Lucas Kerr, Wei Wu, Arunachalam Sekar, Suvendu Giri, Youngmin Chung, Diana Drago-Garcia, Brian P. Danysh, Mattia Lauriola, Michelangelo Fiorentino, Andrea Ardizzoni, Moshe Oren, Collin M. Blakely, Jideofor Ezike, Stefan Wiemann, Laxmi Parida, Trever G. Bivona, Rami Aqeilan, Joan S. Brugge, Aviv Regev, Gad Getz, Eytan Ruppin, Yosef Yarden
Summary: EGFR inhibitors activate endogenous mutators in lung cancer cells, leading to drug resistance. Inhibiting this process can prevent drug resistance.
Review
Medicine, General & Internal
Tai-Huang Lee, Hsiao-Ling Chen, Hsiu-Mei Chang, Chiou-Mei Wu, Kuan-Li Wu, Chia-Yu Kuo, Po-Ju Wei, Chin-Ling Chen, Hui-Lin Liu, Jen-Yu Hung, Chih-Jen Yang, Inn-Wen Chong
Summary: Patients with advanced non-small cell lung cancer (NSCLC) who have susceptible epidermal growth factor receptor (EGFR) mutations and receive combination treatment with EGFR tyrosine kinase inhibitors (TKIs) and anti-angiogenic agents show better progression-free survival (PFS) outcomes, especially among patients with a smoking history or those treated with erlotinib-based therapy. Combination therapy significantly prolongs PFS regardless of ethnicity.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Oncology
Kalyan R. Chitturi, Ethan A. Burns, Ibrahim N. Muhsen, Kartik Anand, Barry H. Trachtenberg
Summary: This review discusses the therapeutic effects of tyrosine kinase inhibitors and monoclonal antibodies targeting the epidermal growth factor receptor, as well as their impact on cardiovascular health. It is apparent that there is limited data regarding the cardiovascular effects of these drugs. Therefore, early cardiovascular screening, close clinical monitoring, and a multidisciplinary approach are needed to minimize the potentially detrimental effects of cardiotoxicity.
CURRENT ONCOLOGY REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Byoung Chul Cho, Dong-Wan Kim, Alexander I. Spira, Jorge E. Gomez, Eric B. Haura, Sang-We Kim, Rachel E. Sanborn, Eun Kyung Cho, Ki Hyeong Lee, Anna Minchom, Jong-Seok Lee, Ji-Youn Han, Misako Nagasaka, Joshua K. Sabari, Sai-Hong Ignatius Ou, Patricia Lorenzini, Joshua M. Bauml, Joshua C. Curtin, Amy Roshak, Grace Gao, John Xie, Meena Thayu, Roland E. Knoblauch, Keunchil Park
Summary: This study evaluated the potential of combining amivantamab and lazertinib in patients with EGFR-mutated NSCLC. The results showed that this combination therapy had improved anti-tumor activity in some patients, with a safety profile similar to monotherapy.
Review
Oncology
Ilana Schlam, Paolo Tarantino, Sara M. Tolaney
Summary: This article summarizes the resistance mechanisms to HER2-targeted treatments and discusses the potential strategies to overcome them in order to improve outcomes for breast cancer patients.
Article
Multidisciplinary Sciences
Hui Deng, Qian Lei, Chengdi Wang, Zhoufeng Wang, Hai Chen, Gang Wang, Na Yang, Dan Huang, Quanwei Yu, Mengling Yao, Xue Xiao, Guonian Zhu, Cheng Cheng, Yangqian Li, Feng Li, Panwen Tian, Weimin Li
Summary: In this study, the authors present a fluorescence-activated cell sorting assay to identify activating EGFR mutations in lung cancer patients and demonstrate its utility in predicting response to EGFR-tyrosine kinase inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Kazuhiko Nakagawa, Ernest Nadal, Edward B. Garon, Makoto Nishio, Takashi Seto, Nobuyuki Yamamoto, Keunchil Park, Jin-Yuan Shih, Luis Paz-Ares, Bente Frimodt-Moller, Annamaria H. Zimmermann, Sameera Wijayawardana, Carla Visseren-Grul, Martin Reck
Summary: In patients with EGFR-mutated NSCLC, the combination treatment of erlotinib and ramucirumab (RAM+ERL) demonstrated significant clinical benefits for both ex19del and ex21L858R mutation types, with similar treatment outcomes and tolerability. Baseline TP53 co-mutation was associated with improved outcomes in both mutation subtypes.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Ursula A. Matulonis, Helen Q. Huang, Virginia L. Filiaci, Marcus Randall, Paul A. DiSilvestro, Katherine M. Moxley, Jeffrey M. Fowler, Matthew A. Powell, Nick M. Spirtos, Krishnansu S. Tewari, William E. Richards, John M. Nakayama, David G. Mutch, David S. Miller, Daniela Matei, Lari B. Wenzel
Summary: Chemotherapy plus radiation did not show superiority over chemotherapy alone in treating stage III or IVA endometrial carcinoma. Although the combined treatment led to a decline in quality of life and gastrointestinal toxicity, these differences were not clinically meaningful.
GYNECOLOGIC ONCOLOGY
(2022)
Meeting Abstract
Oncology
Alexandra Spirtos, Salvatore Lococo, Matthew Carlson, Jayanthi Lea, David Miller, Jessica Lee
GYNECOLOGIC ONCOLOGY
(2022)
Article
Oncology
Brian M. Slomovitz, Virginia L. Filiaci, Joan L. Walker, Michael C. Taub, Karen A. Finkelstein, John W. Moroney, Aimee C. Fleury, Carolyn Y. Muller, Laura L. Holman, Larry J. Copeland, David S. Miller, Robert L. Coleman
Summary: This study evaluated the efficacy and tolerability of everolimus/letrozole and medroxyprogesterone acetate/tamoxifen in the treatment of metastatic endometrial carcinoma. The results showed that both treatment regimens demonstrated clinically meaningful efficacy in patients, especially in chemotherapy-naive patients.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Oncology
Matthew A. Powell, Virginia L. Filiaci, Martee L. Hensley, Helen Q. Huang, Kathleen N. Moore, Krishnansu S. Tewari, Larry J. Copeland, Angeles A. Secord, David G. Mutch, Alessandro Santin, David P. Warshal, Nick M. Spirtos, Paul A. DiSilvestro, Olga B. Ioffe, David S. Miller
Summary: This phase III randomized trial compared the efficacy of paclitaxel and carboplatin (PC) with paclitaxel and ifosfamide (PI) in the treatment of uterine carcinosarcoma. The results showed that PC was not inferior to PI and should be considered as the standard treatment for uterine carcinosarcoma.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Medicine, General & Internal
V Makker, N. Colombo, A. Casado Herraez, A. D. Santin, E. Colomba, D. S. Miller, K. Fujiwara, S. Pignata, S. Baron-Hay, I Ray-Coquard, R. Shapira-Frommer, K. Ushijima, J. Sakata, K. Yonemori, Y. M. Kim, E. M. Guerra, U. A. Sanli, M. M. McCormack, A. D. Smith, S. Keefe, S. Bird, L. Dutta, R. J. Orlowski, D. Lorusso
Summary: Lenvatinib plus pembrolizumab significantly prolongs progression-free survival and overall survival compared to chemotherapy in advanced endometrial cancer patients.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Editorial Material
Obstetrics & Gynecology
Linda Van Le
Summary: This study aimed to compare the efficacy and safety of lenvatinib plus pembrolizumab with chemotherapy in patients with platinum-refractory advanced endometrial cancer. The results showed that lenvatinib plus pembrolizumab significantly improved progression-free survival and overall survival, with better effects observed in pMMR patients. Similar results were observed in the overall population.
OBSTETRICAL & GYNECOLOGICAL SURVEY
(2022)
Meeting Abstract
Oncology
V. Makker, N. Colombo, A. Casado Herraez, B. J. Monk, H. Mackay, A. D. Santin, D. S. Miller, R. G. Moore, S. E. Baron-Hay, I. L. Ray-Coquard, R. Shapira-Frommer, K. Ushijima, K. Yonemori, Y. M. Kim, E. M. Guerra Alia, U. A. Sanli, J. Huang, J. McKenzie, G. Barresi, D. Lorusso
ANNALS OF ONCOLOGY
(2022)
Article
Oncology
Yovanni Casablanca, Guisong Wang, Heather A. Lankes, Chunqiao Tian, Nicholas W. Bateman, Caela R. Miller, Nicole P. Chappell, Laura J. Havrilesky, Amy Hooks Wallace, Nilsa C. Ramirez, David S. Miller, Julie Oliver, Dave Mitchell, Tracy Litzi, Brian E. Blanton, William J. Lowery, John Risinger, Chad A. Hamilton, Neil T. Phippen, Thomas P. Conrads, David Mutch, Katherine Moxley, Roger B. Lee, Floor Backes, Michael J. Birrer, Kathleen M. Darcy, George Larry Maxwell
Summary: This study developed a risk assessment model for metastasis and prognosis in endometrioid endometrial cancer (EEC) using molecular and clinical features. The model, called MS7, showed higher accuracy in predicting the chance of nodal and distant metastasis compared to clinical factors. MS7 score also accurately indicated bad outcomes such as cancer progression and death. This research has important implications for guiding patient care and optimizing treatment strategies for EEC.
Review
Oncology
Ignace Vergote, Teresa Macarulla, Fred R. Hirsch, Carsten Hagemann, David Scott Miller
Summary: Tumor Treating Fields (TTFields) are electric fields that inhibit cancer cell survival and tumor growth without harming healthy cells. TTFields therapy delivers the treatment to the tumor site noninvasively using skin arrays. Taxanes are commonly used chemotherapies that have side effects, and alternative treatments that enhance their efficacy without increasing side effects are needed.
Article
Oncology
Domenica Lorusso, Nicoletta Colombo, Antonio Casado Herraez, Alessandro D. Santin, Emeline Colomba, David Scott Miller, Keiichi Fujiwara, Sandro Pignata, Sally E. Baron-Hay, Isabelle Laure Ray-Coquard, Ronnie Shapira-Frommer, Yong Man Kim, Mary Mccormack, Rachid Massaad, Allison Martin Nguyen, Qi Zhao, Jodi Mckenzie, Vimalanand S. Prabhu, Vicky Makker
Summary: In the phase 3 study 309/KEYNOTE-775, Lenvatinib and pembrolizumab (LEN+PEMBRO) showed significant improvements in efficacy compared to treatment of physician's choice (TPC) for patients with advanced endometrial cancer (aEC). Health-related quality of life (HRQoL) was reported.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Christopher A. Walker, Alexandra N. Spirtos, David S. Miller
Summary: Advanced and recurrent endometrial carcinoma is difficult to treat, especially for patients who are microsatellite stable (MSS) or mismatch repair proficient (pMMR). Recent trials have shown that the combination of pembrolizumab and lenvatinib improves ORR, PFS, and OS compared to current therapies.
EXPERT REVIEW OF ANTICANCER THERAPY
(2023)
Article
Oncology
Steven B. Holloway, Alyssa J. Mercadel, David S. Miller, Jayanthi S. Lea
Summary: This study investigated the impact of para-aortic lymphadenectomy on the outcomes of patients with cervical cancer undergoing surgery. The results showed that omitting para-aortic lymphadenectomy, in the absence of suspicious lymph nodes, did not decrease survival.
GYNECOLOGIC ONCOLOGY
(2023)
Article
Oncology
Vicky Makker, Nicoletta Colombo, Antonio Casado Herraez, Bradley J. Monk, Helen Mackay, Alessandro D. Santin, David S. Miller, Richard G. Moore, Sally Baron-Hay, Isabelle Ray-Coquard, Kimio Ushijima, Kan Yonemori, Yong Man Kim, Eva M. Guerra Alia, Ulus A. Sanli, Steven Bird, Robert Orlowski, Jodi McKenzie, Chinyere Okpara, Gianmaria Barresi, Domenica Lorusso
Summary: This article reports the final prespecified analysis of the Study 309/KEYNOTE-775, which is an open-label, randomized, phase III trial. The results show that lenvatinib plus pembrolizumab improves overall survival, progression-free survival, and objective response rate compared to chemotherapy in patients with advanced endometrial cancer. The combination therapy also demonstrates improved efficacy and manageable safety in various subgroups.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Meeting Abstract
Oncology
Vicky Makker, Nicoletta Colombo, Antonio Casado Herraez, Bradley Monk, Helen Mackay, Alessandro Santin, David Miller, Richard Moore, Isabelle Ray-Coquard, Ronnie Shapira-Frommer, Kimio Ushijima, Kan Yonemori, Yong Man Kim, Eva Guerra Alia, Ulus Sanli, Ran Xie, Melissa Zale, Jodi Mckenzie, Gianmaria Barresi, Domenica Lorusso
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2022)
Meeting Abstract
Oncology
Vicky Makker, Nicoletta Colombo, Alessandro Santin, David Scott Miller, Keiichi Fujiwara, Sandro Pignata, Isabelle Laure Ray-Coquard, Yong Man Kim, Eva M. Guerra, Jie Huang, Gianmaria Barresi, Jodi McKenzie, Domenica Lorusso
JOURNAL OF CLINICAL ONCOLOGY
(2022)