Nature Reviews Clinical Oncology

Tisotumab vedotin effective in recurrent cervical cancer

Pembrolizumab plus chemoradiotherapy effective in locally advanced cervical cancer

Non-inferiority of simple versus radical hysterectomy in low-risk cervical cancer

Neoadjuvant chemoimmunotherapy is effective in locally advanced cervical cancer

Viral gene therapy active in ovarian cancer

First-line PARP inhibition in ovarian cancer — standard of care for all?

Prospective evidence discourages secondary cytoreductive surgery

Pembrolizumab tunes up chemotherapy in cervical cancer

From AACR 2021

WEE1 inhibition after platinum resistance

SCRT for early stage cervical cancer

Benefit with cemiplimab in cervical cancer

Global epidemiology of epithelial ovarian cancer

Globally, ovarian cancer is the eighth most common cancer in women, accounting for an estimated 3.7% of cases and 4.7% of cancer deaths in 2020. Until the early 2000s, age-standardized incidence was highest in northern Europe and North America, but this trend has changed; incidence is now declining in these regions and increasing in parts of eastern Europe and Asia. Ovarian cancer is a very heterogeneous disease and, even among the most common type, namely epithelial ovarian cancer, five major clinically and genetically distinct histotypes exist. Most high-grade serous ovarian carcinomas are now recognized to originate in the fimbrial ends of the fallopian tube. This knowledge has led to more cancers being coded as fallopian tube in origin, which probably explains some of the apparent declines in ovarian cancer incidence, particularly in high-income countries; however, it also suggests that opportunistic salpingectomy offers an important opportunity for prevention. The five histotypes share several reproductive and hormonal risk factors, although differences also exist. In this Review, we summarize the epidemiology of this complex disease, comparing the different histotypes, and consider the potential for prevention. We also discuss how changes in the prevalence of risk and protective factors might have contributed to the observed changes in incidence and what this might mean for incidence in the future.

The ten genes for breast (and ovarian) cancer susceptibility

Immunotherapy for ovarian cancer: towards a tailored immunophenotype-based approach

Despite documented evidence that ovarian cancer cells express immune-checkpoint molecules, such as PD-1 and PD-L1, and of a positive correlation between the presence of tumour-infiltrating lymphocytes and favourable overall survival outcomes in patients with this tumour type, the results of trials testing immune-checkpoint inhibitors (ICIs) in these patients thus far have been disappointing. The lack of response to ICIs can be attributed to tumour heterogeneity as well as inherent or acquired resistance associated with the tumour microenvironment (TME). Understanding tumour immunobiology, discovering biomarkers for patient selection and establishing optimal treatment combinations remains the hope but also a key challenge for the future application of immunotherapy in ovarian cancer. In this Review, we summarize results from trials testing ICIs in patients with ovarian cancer. We propose the implementation of a systematic CD8

Translating biological insights into improved management of endometrial cancer

Endometrial cancer (EC) is the most common gynaecological cancer among women in high-income countries, with both incidence and mortality continuing to increase. The complexity of the management of patients with EC has evolved with greater comprehension of the underlying biology and heterogeneity of this disease. With a growing number of novel therapeutic agents available, emerging treatment regimens seem to have the potential to help to address the concerning trends in EC-related mortality. In this Review, we describe the epidemiology, histopathology and molecular classification of EC as well as the role of the new (2023) International Federation of Gynecologists and Obstetricians (FIGO) staging model. Furthermore, we provide an overview of disease management in the first-line and recurrent disease settings. With increasing use of molecular profiling and updates in treatment paradigms, we also summarize new developments in this rapidly changing treatment landscape.

Exploiting the folate receptor α in oncology

Folate receptor α (FRα) came into focus as an anticancer target many decades after the successful development of drugs targeting intracellular folate metabolism, such as methotrexate and pemetrexed. Binding to FRα is one of several methods by which folate is taken up by cells; however, this receptor is an attractive anticancer drug target owing to the overexpression of FRα in a range of solid tumours, including ovarian, lung and breast cancers. Furthermore, using FRα to better localize effective anticancer therapies to their target tumours using platforms such as antibody-drug conjugates, small-molecule drug conjugates, radioimmunoconjugates and, more recently, chimeric antigen receptor T cells could further improve the outcomes of patients with FRα-overexpressing cancers. FRα can also be harnessed for predictive biomarker research. Moreover, imaging FRα radiologically or in real time during surgery can lead to improved functional imaging and surgical outcomes, respectively. In this Review, we describe the current status of research into FRα in cancer, including data from several late-phase clinical trials involving FRα-targeted therapies, and the use of new technologies to develop FRα-targeted agents with improved therapeutic indices.

Treatment advances across the cervical cancer spectrum

Cervical cancer is preventable with screening and vaccination approaches; however, access to these preventative measures is limited both nationally and globally and thus many women will still develop cervical cancer. Novel treatments and practice-changing research have improved cervical cancer outcomes over the past few decades. In this Review, we discuss clinical trials that have refined or redefined the treatment of cervical cancers across the early stage, locally advanced, persistent, recurrent and/or metastatic disease settings. Advances for patients with early stage disease have been achieved through trials evaluating less extensive and fertility-preserving surgeries, different surgical approaches (open versus minimally invasive), and sentinel versus full pelvic lymph node dissection. We also discuss results from trials testing the use of neoadjuvant, induction and adjuvant chemotherapy as well as immune-checkpoint inhibitors in patients with locally advanced disease. Finally, we review the progress made with systemic chemotherapy and novel therapeutics, including anti-angiogenic agents, immune-checkpoint inhibitors and antibody-drug conjugates, in the setting of metastatic and/or recurrent cervical cancer. The advances highlighted in this manuscript have reduced morbidity and improved overall survival for patients with this challenging-to-treat disease, while also inspiring additional research and trials in the field.

Epidemiology of HPV-associated cancers past, present and future: towards prevention and elimination

Cervical cancer is the first cancer deemed amenable to elimination through prevention, and thus lessons from the epidemiology and prevention of this cancer type can provide information on strategies to manage other cancers. Infection with the human papillomavirus (HPV) causes virtually all cervical cancers, and an important proportion of oropharyngeal, anal and genital cancers. Whereas 20th century prevention efforts were dominated by cytology-based screening, the present and future of HPV-associated cancer prevention relies mostly on HPV vaccination and molecular screening tests. In this Review, we provide an overview of the epidemiology of HPV-associated cancers, their disease burden, how past and contemporary preventive interventions have shaped their incidence and mortality, and the potential for elimination. We particularly focus on the cofactors that could have the greatest effect on prevention efforts, such as parity and human immunodeficiency virus infection, as well as on social determinants of health. Given that the incidence of and mortality from HPV-associated cancers remain strongly associated with the socioeconomic status of individuals and the human development index of countries, elimination efforts are unlikely to succeed unless prevention efforts focus on health equity, with a commitment to both primary and secondary prevention.

Heterogeneity and treatment landscape of ovarian carcinoma

Ovarian carcinoma is characterized by heterogeneity at the molecular, cellular and anatomical levels, both spatially and temporally. This heterogeneity affects response to surgery and/or systemic therapy, and also facilitates inherent and acquired drug resistance. As a consequence, this tumour type is often aggressive and frequently lethal. Ovarian carcinoma is not a single disease entity and comprises various subtypes, each with distinct complex molecular landscapes that change during progression and therapy. The interactions of cancer and stromal cells within the tumour microenvironment further affects disease evolution and response to therapy. In past decades, researchers have characterized the cellular, molecular, microenvironmental and immunological heterogeneity of ovarian carcinoma. Traditional treatment approaches have considered ovarian carcinoma as a single entity. This landscape is slowly changing with the increasing appreciation of heterogeneity and the recognition that delivering ineffective therapies can delay the development of effective personalized approaches as well as potentially change the molecular and cellular characteristics of the tumour, which might lead to additional resistance to subsequent therapy. In this Review we discuss the heterogeneity of ovarian carcinoma, outline the current treatment landscape for this malignancy and highlight potentially effective therapeutic strategies in development.

Cytoreductive surgery effective after relapse

Mirvetuximab soravtansine has activity in platinum-sensitive epithelial ovarian cancer

Mirvetuximab soravtansine superior to chemotherapy in platinum-resistant epithelial ovarian cancer

Adding immune-checkpoint inhibitors to chemotherapy extends survival in endometrial cancer

Survival benefit with second-line combination in endometrial cancer