Trends in Cancer

Uncovering Mitochondrial Determinants of Racial Disparities in Ovarian Cancer

Ovarian cancer (OC) incidence and mortality rates differ between racial groups. Mitochondrial genetic factors are now emerging as determinants of racial disparities in OC. A comprehensive understanding of the role of mitochondria in OC health disparities will help in developing novel therapeutic strategies targeting mitochondria to reduce or eliminate racial health disparities.

Tissue-Specific Carcinogens as Soil to Seed BRCA1/2-Mutant Hereditary Cancers

Despite their ubiquitous expression, the inheritance of monoallelic germline mutations in breast cancer susceptibility gene type 1 or 2 (BRCA1/2) poses tissue-specific variations in cancer risks and primarily associate with familial breast and ovarian cancers. The molecular basis of this tissue-specific tumor incidence remains unknown and intriguing to cancer researchers. A plethora of recent reports support the idea that several nongenetic factors present in the tissue microenvironment could induce tumors in the mutant BRCA1/2 background. This Opinion article summarizes the recent advances on tissue-specific carcinogens and their complex crosstalk with the compromised DNA repair machinery of BRCA1/2-mutant cells. Finally, we present our perspective on the therapeutic and chemopreventive interpretations of these developments.

Multimodal immunostimulation to control BRCA1-defective ovarian carcinoma

Depending on intensity and duration, STING1 (stimulator of interferon response cGAMP interactor 1) signaling can restrain or promote tumor progression via both cancer cell-intrinsic and -extrinsic pathways. Bruand et al. recently identified a novel STING1-driven immunosuppressive pathway that can be targeted toward superior disease control in preclinical models of homologous recombination deficient (HRD) ovarian carcinoma.

Crosstalk of T cells within the ovarian cancer microenvironment

Ovarian cancer (OC) represents ecosystems of highly diverse tumor microenvironments (TMEs). The presence of tumor-infiltrating lymphocytes (TILs) is linked to enhanced immune responses and long-term survival. In this review we present emerging evidence suggesting that cellular crosstalk tightly regulates the distribution of TILs within the TME, underscoring the need to better understand key cellular networks that promote or impede T cell infiltration in OC. We also capture the emergent methodologies and computational techniques that enable the dissection of cell-cell crosstalk. Finally, we present innovative ex vivo TME models that can be leveraged to map and perturb cellular communications to enhance T cell infiltration and immune reactivity.

Immunological control of ovarian carcinoma by chemotherapy and targeted anticancer agents

At odds with other solid tumors, epithelial ovarian cancer (EOC) is poorly sensitive to immune checkpoint inhibitors (ICIs), largely reflecting active immunosuppression despite CD8

Molecular and clinical insights into early-onset endometrial cancer

The global incidence of endometrial cancer is on the rise, marked by a notable surge in early-onset endometrial cancer (EOEC; age at diagnosis <50 years). By contrast to late-onset cases, EOEC displays distinct clinical, pathological, and molecular characteristics. The enhanced understanding of the disease's pathophysiology, enabling a more precise differentiation between low-risk and high-risk patients, could facilitate the establishment of risk-stratified treatments that preserve ovarian function and fertility in low-risk EOEC cases. In this review, we delve into the distinctive epidemiological, molecular, and clinical characteristics of EOEC, as well as early noninvasive screening and fertility preservation treatments.

Interferon epsilon and ovarian cancer

Most biologists know of the interferons IFNα, IFNβ, and IFNγ and their roles in immunity and infection, but they may not have heard of IFNε. A recent study in Nature suggests that IFNε can act as a tumor suppressor in serous ovarian cancers.

Bacteria-derived L-lactate fuels cervical cancer chemoradiotherapy resistance

Accumulating studies have demonstrated the presence of viable and metabolically active bacterial communities within a range of solid tumor types. However, the precise mechanisms by which these microbes modulate their infected tumor niches or impact patient responses to cancer treatments remain to be elucidated. Recently, Colbert et al. revealed that L-lactate produced by intratumoral Lactobacillus iners reprograms metabolic capabilities of cervical tumors to support chemoradiotherapy resistance. This finding has implications for many solid cancer types.

Immunotherapeutic Transport Oncophysics: Space, Time, and Immune Activation in Cancer

Immuno-oncology has gained momentum thanks to the success of strategies aimed at enhancing immune-mediated antitumor response. The field of immunotherapeutic transport oncophysics investigates the physical processes that drive cancer immunotherapies. This review discusses three main aspects that determine the outcome of an immunotherapy-based treatment from a physical point of view; (i) space, the distribution of cancer and immune cells within tumor masses, (ii) time, the temporal dynamic of immune response against tumors, and (iii) activity, the ability of immune cell populations to suppress cancer. Upon introducing these topics with examples from the literature, we investigate in detail two cases where the interplay between space, time, and activation variables determines immune response: nanodendritic cell vaccines and immunosuppression in ovarian cancer.