Featured
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Article
| Open Access
Prediction of recurrence risk in endometrial cancer with multimodal deep learning
A multimodal deep learning prognostic model based on histopathology outperforms current gold standards for identifying patients with endometrial cancer with different outcomes, in multiple external validation cohorts.
- Sarah Volinsky-Fremond
- , Nanda Horeweg
- & Tjalling Bosse
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Article |
Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial
In a prespecified interim analysis of the multicenter, randomized, phase 3 FLAMES trial, maintenance therapy with a PARP inhibitor in patients with ovarian cancer showed prolonged progression-free survival compared with placebo in all subgroups defined by BRCA or homologous recombination status.
- Xiaohua Wu
- , Jihong Liu
- & Linjuan Zeng
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News & Views |
Implementing plans for global elimination of cervical cancer
Evidence supports the use of primary HPV testing to accelerate the global elimination of cervical cancer, but such recommendations must be viewed in the context of the fragile healthcare systems and complex implementation challenges in low-income and lower-middle income countries.
- Diama Bhadra Vale
- & Julio Cesar Teixeira
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Article
| Open Access
Benefits and harms of cervical screening, triage and treatment strategies in women living with HIV
A model evaluating cervical screening, triage and treatment strategies to prevent cervical cancer in women living with HIV in Tanzania provides evidence to support the World Health Organization’s recommendation of primary HPV testing starting at age 25 years with 3–5-year regular screening intervals.
- Michaela T. Hall
- , Kate T. Simms
- & Karen Canfell
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Research Highlight |
A new, affordable HPV vaccine
A quadrivalent vaccine against human papillomavirus produced by the Serum Institute of India was shown to be noninferior to the established quadrivalent vaccine — boosting global efforts to eliminate cervical cancer.
- Karen O’Leary
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Article
| Open Access
The PD-1- and LAG-3-targeting bispecific molecule tebotelimab in solid tumors and hematologic cancers: a phase 1 trial
The bispecific molecule tebotelimab, which blocks both PD-1 and LAG-3, is well tolerated as a monotherapy and in combination with the anti-HER-2 antibody margetuximab and elicits encouraging clinical activity in solid tumors with high LAG-3 levels and/or expression of IFN-γ-regulated genes.
- Jason J. Luke
- , Manish R. Patel
- & Paul A. Moore
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Article
| Open Access
Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results
T cells containing an anti-mesothelin single-domain antibody fused to a component of the endogenous T cell receptor signaling complex exhibit notable toxicities but encouraging clinical responses in patients with treatment-refractory mesothelioma and ovarian cancer.
- Raffit Hassan
- , Marcus Butler
- & David Hong
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Research Highlight |
A biomarker-driven therapy for ovarian cancer
An antibody–drug conjugate showed impressive anti-cancer activity in selected patients with platinum-resistant ovarian cancer, and could become a new standard of care.
- Karen O’Leary
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Article
| Open Access
Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: a phase 1 trial
In a phase 1 dose-escalation trial in patients with nine different types of solid tumors, MAGE-A4-specific T cells had an acceptable safety profile and exhibited an encouraging overall response rate in patients with synovial sarcoma.
- David S. Hong
- , Brian A. Van Tine
- & Marcus O. Butler
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Research Highlight |
Single vaccine shot protects against cervical cancer
A WHO expert panel concluded that a single dose of HPV vaccine has efficacy comparable to that of the two-dose regimen, which could help boost cervical cancer–elimination efforts.
- Karen O’Leary
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Letter |
TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers
In a first-in-human phase 1 trial of patients with HPV-associated metastatic epithelial cancers, T cells targeting HPV-16 E7 were well tolerated, with one observed dose-limiting toxicity, and elicited objective clinical responses in 6 of 12 treated patients.
- Nisha B. Nagarsheth
- , Scott M. Norberg
- & Christian S. Hinrichs
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Letter |
A single-cell landscape of high-grade serous ovarian cancer
Single-cell transcriptomics analysis of malignant ascites samples from patients with high-grade serous ovarian cancer reveals inter- and intra-patient heterogeneity in malignant cells, cancer-associated fibroblasts and macrophages.
- Benjamin Izar
- , Itay Tirosh
- & Aviv Regev
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Resource |
An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity
A biobank of ovarian cancer organoids recapitulates the histopathological and molecular hallmarks of patient tumors and provides a resource for preclinical research.
- Oded Kopper
- , Chris J. de Witte
- & Hans Clevers
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News & Views |
SPOP tips the balance of BETs in cancer
Cancer-associated mutations in speckle-type POZ (pox virus and zinc-finger) protein confer neomorphic activity, altering its substrate affinities and its response to bromodomain and extraterminal inhibitors in prostate and endometrial cancer.
- Katie A Fennell
- & Mark A Dawson
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Article |
p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity
Silencing expression of the long noncoding RNA NEAT1 prevents paraspeckle formation and sensitizes neoplastic cells to DNA-damage-induced cell death. NEAT1 expression also predicts chemotherapy response in ovarian cancer patients.
- Carmen Adriaens
- , Laura Standaert
- & Jean-Christophe Marine
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Article |
Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers
Ovarian tumors with common mutations in the epigenetic regulator ARID1A are shown to be sensitive to inhibition of EZH2, another epigenetic regulator, showing a synthetic lethality that could potentially be exploited therapeutically
- Benjamin G Bitler
- , Katherine M Aird
- & Rugang Zhang
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Article |
Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors
Tumors use numerous mechanisms to escape detection and killing by the immune system. George Coukos and colleagues now report that cancer cells can also co-opt tumor-associated endothelial cells to prevent immune eradication. The researchers show that factors secreted by cancer cells induce increased expression of Fas ligand on the tumor endothelium, resulting in killing of CD8+ effector T cells and thereby facilitating immune escape and tumor growth.
- Gregory T Motz
- , Stephen P Santoro
- & George Coukos
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Community Corner |
The value of HPV vaccination
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News & Views |
Stressed tumor cell, chemosensitized cancer
miR-200 family expression results in highly proliferative ovarian cancer cells. Yet this expression is also linked to longer overall survival in women with ovarian cancer. A new study sheds light into this apparent paradox showing that two members of this family—miR-141 and miR-200a—not only boost tumor growth but also sensitize tumor cells to chemotherapy (pages 1627–1635).
- Erik A C Wiemer
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Article |
miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response
This report identifies a new contribution of members of the miR-200 family to tumorigenesis. miR-200a and miR-141 specifically regulate p38α, contributing to the cellular modulation of oxidative stress responses. In this role, the miRs can accelerate ovarian tumorigenesis but also endow cancer cells with increased sensitivity to ROS-inducing chemotherapy. This two-part effect is reflected on the distinct association of the miRs with patient survival and may be informative for treatment decisions.
- Bogdan Mateescu
- , Luciana Batista
- & Fatima Mechta-Grigoriou
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Letter |
Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth
Ovarian tumors preferentially metastasize to the omentum, a peritoneal fat layer. This report proposes that the reasons for this predilection stem from the growth advantage conferred by adipocytes on ovarian cancer cells. Adipocytes seem to promote homing of cancer cells through adipokine secretion, and direct contact of the two cell types promotes metabolic changes that result in lipid transfer from adipocytes to tumor cells. Environmental-driven metabolic adaptations could be exploited to target omental metastasis.
- Kristin M Nieman
- , Hilary A Kenny
- & Ernst Lengyel
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Technical Report |
Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results
The prognosis for patients with advanced stage ovarian cancer is poor. Here, Gooitzen van Dam and colleagues demonstrate the first human application of a tumor-specific intraoperative fluorescence imaging methodology using a folate receptor-α (FR-α)-targeted fluorescent agent that exploits the overexpression of FR-α in the majority of epithelial ovarian cancers. It is hoped this approach may lead to improved intraoperative staging and more radical cytoreductive surgery.
- Gooitzen M van Dam
- , George Themelis
- & Vasilis Ntziachristos
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Surgery versus no surgery in platinum-sensitive relapsed ovarian cancer: final overall survival analysis of the SOC-1 randomized phase 3 trial
Cancer vaccine boosted by infrastructure for HIV care in Africa
Fewer shots proposed to increase uptake of HPV vaccine