The use of brachytherapy for the treatment of gynecologic malignancies, particularly cervical cancer, has a long and rich history that is nearly as long as the history of radiation oncology itself. From the first gynecologic brachytherapy treatments in the early 20th century to the modern era, significant transformation has occurred driven largely by advancements in technology. The development of high-dose rate sources, remote afterloaders, novel applicators, and 3-dimensional image guidance has led to improved local control, and thus improved survival, solidifying the role of brachytherapy as an integral component in the treatment of locally advanced cervical cancer. Current research efforts examining novel magnetic resonance imaging sequences, active magnetic resonance tracking, and the application of hydrogel aim to further improve local control and reduce treatment toxicity.In recent years, magnetic resonance imaging (MRI) has become one of the standard imaging tools to define the macroscopic gross tumor volume in locally advanced cervical cancer patients based on T2-weighted sequence. Elafibranor PPAR agonist suggest that functional MRI could be used to potentially improve the delineation of target volumes based on physiologic features, defining radioresistant subvolumes that may require higher doses to achieve local cure. Functional imaging can be used to predict tumor biology and outcome, as well as for assessment of tumor response during radiotherapy. The concept of adaptive radiotherapy relies on the possibility of monitoring variations in target volumes structures to guide treatment-plan modification during radiotherapy, taking into account not only internal movements but also tumor response. With integrated MRI in radiotherapy linear accelerators, motion monitoring during treatment delivery has become available. MRI can be also used to accurately evaluate cervical tumor residual volume after chemoradiotherapy, and therefore allowing a personalized treatment planning for brachytherapy boost, based on tumor radiosensitivity. In this review, we discuss how MRI tumor response assessment could be included into clinical practice during radiation therapy in locally advanced cervical cancer patients.The clinical, molecular, and genetic heterogeneity of uterine cervix cancers makes the discovery of effective therapies a challenge. Optimal evaluation of effective radiotherapy-agent combinations requires sophisticated trial strategies from the United States National Cancer Institute and its pharmaceutical collaborators. One strategy involves the phase 0 trial, which falls under the United States Food and Drug Administration Exploratory Investigational New Drug Guidance, or xIND. As currently envisioned for radiotherapy-based trials, the phase 0 trial provides a platform for study of pharmacodynamic effects linked to pharmacokinetic exposures, designed to screen a new experimental agent’s dose or schedule, in combination with standard radiotherapy regimens, in a very small number (10-15) of subjects. In the phase 0 trial, radiotherapy-agent combinations are intended to be biologically active, but a new experimental agent’s low dose or infrequent schedule is considered nontoxic and nonbeneficial. The phase 0 trial primary endpoint is an individual subject’s pharmacodynamic response. Regimens move on from phase 0 trial development if and when a predetermined all-subject pharmacodynamic response rate is crossed. An initial safety experience during and after the radiotherapy-agent combination determines future feasibility. For this article, the clinical example of women with abdominopelvic lymph node-positive uterine cervix cancer is used to elaborate the phase 0 trial approach to the discovery of novel radiosensitizing oncological agents. It is expected that phase 0 radiotherapy-agent trials will become more prevalent in near-term clinical development.Outcomes for women with node-positive, recurrent, and metastatic cervical cancer remain poor. Persistent infection by the human papilloma virus is related to disordered interactions with the immune system and development of cervical cancer, making the resultant malignancy an attractive target for immunotherapy. Various types of immunomodulatory treatments have been studied, including a bacterial vaccine vector and T cell therapy. Immune checkpoint blockade has shown promise in the recurrent or metastatic settings, and in combination with chemoradiotherapy for definitive treatment with acceptable toxicity profiles. Ongoing trials are investigating timing, dosing, and combinations of immunomodulatory treatments, with potential to improve survival and advance our understanding of the immune system’s role in combating cervical cancer.Definitive standard chemoradiation for locoregionally advanced carcinomas of the uterine cervix includes multimodality therapy consisting of concurrent cisplatin based chemoradiation comprising of external-beam radiotherapy with systemic chemotherapy followed by intracavitary brachytherapy. New developments in radiotherapy, such as intensity-modulated radiotherapy, which aim to improve tumor control rates and reduce associated toxicity have reopened the discussion regarding the benefit of intensification of concomitant or sequential systemic therapy in the treatment of cervical cancer. Intensification of systemic chemotherapy used in standard chemoradiation for cervical cancer is an attractive approach to improve disease control, but given the concerns regarding toxicity deserves further evaluation to ensure their safe use in patients. This is a review of published and ongoing studies investigating intensification of systemic chemotherapy in the treatment of locally advanced cervical cancer.We have studied the mode of action of the insecticide spirotetramat in the nematode Caenorhabditis elegans. A combination of symptomology, forward genetics and genome editing show that spirotetramat acts on acetyl-CoA carboxylase (ACC) in C. elegans, as it does in insects. We found C. #link# elegans embryos exposed to spirotetramat show a cell division defect which closely resembles the phenotype of loss-of-function mutations in the gene pod-2, which encodes ACC. We then identified two mutations in the carboxyl transferase domain of pod-2 (ACC) which confer resistance and were confirmed using CRISPR/Cas9. One of these mutations substitutes an invertebrate-specific amino acid with one ubiquitous in other taxa; this residue may, therefore, be a determinant of the selectivity of spirotetramat for invertebrates. Such a mutation may also be the target of selection for resistance in the field. Our study is a further demonstration of the utility of C. elegans in studying bioactive chemicals.