The target invites a foe: antibody–drug conjugates in gynecologic oncology

Purpose of review Antibody–drug conjugates (ADCs) represent a promising new class of cancer therapeutics. Currently more than 60 ADCs are in clinical development, however, only very few trials focus on gynecologic malignancies. In this review, we summarize the most recent advances in ADC drug development with an emphasis on how this progress relates to patients diagnosed with gynecologic malignancies and breast cancer. Recent findings The cytotoxic payloads of the majority of the ADCs that are currently in clinical trials for gynecologic malignancies or breast cancer are auristatins (MMAE, MMAF), maytansinoids (DM1, DM4), calicheamicin, pyrrolobenzodiazepines and SN-38. Both cleavable and noncleavable linkers are currently being investigated in clinical trials. A number of novel target antigens are currently being validated in ongoing clinical trials including folate receptor alpha, mesothelin, CA-125, NaPi2b, NOTCH3, protein tyrosine kinase-like 7, ephrin-A4, TROP2, CEACAM5, and LAMP1. For most ADCs currently in clinical development, dose-limiting toxicities appear to be unrelated to the targeted antigen but more tightly associated with the payload. Rational drug design involving optimization of the antibody, the linker and the conjugation chemistry is aimed at improving the therapeutic index of new ADCs. Summary Antibody–drug conjugates can increase the efficacy and decrease the toxicity of their payloads in comparison with traditional cyctotoxic agents....
Source: Current Opinion in Obstetrics and Gynecology - Category: OBGYN Tags: GYNECOLOGIC ONCOLOGY: Edited by Gottfried E. Konecny Source Type: research

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Authors: Suh DH, Kim M, Lee KH, Eom KY, Kjeldsen MK, Mirza MR, Kim JW Abstract In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and ...
Source: Journal of Gynecologic Oncology - Category: OBGYN Tags: J Gynecol Oncol Source Type: research
Purpose of review Antibody–drug conjugates (ADCs) represent a promising new class of cancer therapeutics. Currently more than 60 ADCs are in clinical development, however, only very few trials focus on gynecologic malignancies. In this review, we summarize the most recent advances in ADC drug development with an emphasis on how this progress relates to patients diagnosed with gynecologic malignancies and breast cancer. Recent findings The cytotoxic payloads of the majority of the ADCs that are currently in clinical trials for gynecologic malignancies or breast cancer are auristatins (MMAE, MMAF), maytansinoids (...
Source: Current Opinion in Obstetrics and Gynecology - Category: OBGYN Tags: GYNECOLOGIC ONCOLOGY: Edited by Gottfried E. Konecny Source Type: research
Authors: Razia S, Nakayama K, Tsukao M, Nakamura K, Ishikawa M, Ishibashi T, Ishikawa N, Sanuki K, Yamashita H, Ono R, Hossain MM, Minamoto T, Kyo S Abstract Haematogenous metastases of breast cancer tumors has previously been demonstrated to frequently occur at the sites of the lung, bones, liver and brain, however presence in the uterine remains a rare occurrence. Metastatic carcinoma of the uterus usually originates from other genital sites, most frequently from the ovaries. The current review presents the first reported case of lobular breast carcinoma metastasizing to an endometrial polyp, the cervix and a lei...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Conclusions: Clomiphene citrate appears associated with increased risk of ovarian and endometrial cancer. Elevations in risks of breast and thyroid cancer were less consistent across type of drug exposure and parity. Impact: Continued monitoring of fertility treatments is warranted. Cancer Epidemiol Biomarkers Prev; 26(6); 953–62. ©2017 AACR.
Source: Cancer Epidemiology Biomarkers and Prevention - Category: Cancer & Oncology Authors: Tags: Research Articles Source Type: research
Results from an open-label, phase 2, basket trial assessing the clinical activity of neratinib in 141 patients with either HER2-mutant or HER3-mutant tumours were presented by David Hyman (Memorial Sloan Kettering Cancer Center, New York, NY, USA). Patients with HER2-mutant lung cancer (n=26), breast cancer (n=25), bladder or urinary tract cancer (n=16), colorectal cancer (n=12), biliary tract cancer (n=9), endometrial cancer (n=7), cervical cancer (n=5), gastro-oesophageal cancer (n=5), and ovarian cancer (n=4), as well as patients with solid tumours not otherwise specified (n=32; of which 15 were HER2-mutant-postive and ...
Source: The Lancet Oncology - Category: Cancer & Oncology Authors: Tags: News Source Type: research
Authors: Suh DH, Kim M, Kim K, Kim HJ, Lee KH, Kim JW Abstract In 2016, 13 topics were selected as major research advances in gynecologic oncology. For ovarian cancer, study results supporting previous ones regarding surgical preventive strategies were reported. There were several targeted agents that showed comparable responses in phase III trials, including niraparib, cediranib, and nintedanib. On the contrary to our expectations, dose-dense weekly chemotherapy regimen failed to prove superior survival outcomes compared with conventional triweekly regimen. Single-agent non-platinum treatment to prolong platinum-f...
Source: Journal of Gynecologic Oncology - Category: OBGYN Tags: J Gynecol Oncol Source Type: research
Conclusion We found an increased risk of NMSC, breast cancer, and hepatic cancer, and a reduced risk of lung cancer, among patients with rosacea. These results are in contrast to the limited published data on cancers in rosacea, and further studies are warranted to elucidate the potential relationship between rosacea and various cancers. The findings add to the overall clinical description of patients with rosacea.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Venerated journalist and anchor Gwen Ifill died Monday at the age of 61. The cause of death was endometrial cancer, with which she was diagnosed less than a year ago.  Endometrial cancer has a reputation for being one of the most treatable and least-lethal gynecological cancers that women face. But as Ifill’s case shows, a significant minority of cases can be aggressive and fast-paced ― and they’re more likely to be concentrated among black women. For women who have recurrent endometrial cancer, doctors have few medications that can specifically target growth.  “We don’t have as many too...
Source: Science - The Huffington Post - Category: Science Source Type: news
Authors: Kuloglu T, Celik O, Aydin S, Hanifi Ozercan I, Acet M, Aydin Y, Artas G, Turk A, Yardim M, Ozan G, Hanifi Yalcin M, Kocaman N Abstract To determine expression pattern of irisin in tissues obtained from human ovarian cancer, breast cancer, and cervix cancer. Tissue samples obtained from subjects with breast cancer, ovarian cancer cervix cancer, simple endometrial hyperplasia, complex atypical endometrial hyperplasia. At least five sections from each subject were immunohistochemically stained with irisin antibody, and H-score method was used to evaluate irisin intensity. Tissues obtained from healthy breast ...
Source: Cellular and Molecular Biology - Category: Molecular Biology Tags: Cell Mol Biol (Noisy-le-grand) Source Type: research
Conclusions: These findings indicate that there are significant disparities in cancer incidence and mortality by geography and ancestry in TT. The differences in the top cancer sites in TT compared to United States and other countries as well as the increasing cancer burden highlights the need for increased cancer research in the Caribbean. Our findings also highlight the need for further studies including planned molecular, genetic, and environmental studies, to further understand risk factors related to these differences or disparities in cancer burden in TT. These and other similar efforts will aid TT in strategies for ...
Source: Cancer Epidemiology Biomarkers and Prevention - Category: Cancer & Oncology Authors: Tags: General Epidemiology and Biostatistics: Poster Presentations - Proffered Abstracts Source Type: research
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