Current evidence on regulated cell death pathways in ovarian cancer is summarized, with emphasis on key regulators, mechanistic links to treatment resistance, potential biomarkers, and the limitations that currently restrict clinical translation.
Abstract
Ovarian cancer is one of the most lethal malignancies of the female reproductive system, largely because many patients are diagnosed at an advanced stage and eventually develop recurrent or treatment-resistant disease. Although cytoreductive surgery, platinum-based chemotherapy, PARP inhibitors, anti-angiogenic agents, and immunotherapy have improved management for selected patients, relapse and drug resistance remain major clinical barriers. Regulated cell death pathways, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, disulfidptosis, and autophagy-dependent cell death, are increasingly recognized as contributors to ovarian cancer progression, immune regulation, and therapeutic response. This review summarizes current evidence on these pathways in ovarian cancer, with emphasis on key regulators, mechanistic links to treatment resistance, potential biomarkers, and the limitations that currently restrict clinical translation.
This review systematically outlines the mechanistic underpinnings of multiple major RCD subtypes in OC, with a focused summary of advances in innovative small-molecule compounds targeting these pathways, to provide novel insights and directions for precision therapy in OC.
Yu Liu, Z. Geng, Baofu Jia et al.· Frontiers in Cell and Develo...· 0 citations
Ovarian cancer (OC) is the seventh most prevalent type of cancer in women and one of the most lethal gynecological malignancies, due to the poor prognosis (with a 5-year survival rate of about 50%), the lack of specific clinical symptoms, the absence of effective screening, and the fact that the tumor grows without obvious signs. These factors complicate early detection, when clinical intervention is most effective, leading to late diagnosis. Standard treatment for OC includes cytoreductive surgery followed by platinum-based chemotherapy (PBC) with carboplatin and paclitaxel or their analogs. Conversely, despite the initial positive response to chemotherapy, many patients experience disease recurrence and develop chemotherapy resistance, which makes long-term treatment challenging and often results in fatal outcomes. Here, we focus on therapeutic strategies that overcome this resistance by precisely targeting pathways of programmed cell death (PCD), thereby opening new avenues for treatment. The potential of using PCD in OC treatment is being considered, focusing on key regulatory mechanisms: triggering intrinsic and/or extrinsic apoptosis; the complex role of autophagy in both promoting survival and inducing cell death; the emerging relevance of ferroptosis activation through inhibition of GPX4 or blockade of Xc- system; and the potential of using necroptosis and pyroptosis as immunogenic PCD modalities that can activate an immune response against the tumor. The use of these different PCD pathways offers opportunities to sensitize resistant tumors and improve patient outcomes.
Aygun R. Mamedova, G. Kopeina, B. Zhivotovsky et al.· Cell Death & Disease· 0 citations
The evolving biological basis of therapeutic resistance is examined and how emerging treatment strategies may be integrated into biologically informed clinical development is discussed to improve patient selection, guide therapeutic sequencing, and increase the durability of treatment benefit in extensive-stage SCLC.
Jun Kim, Seounghun Kang· Pharmaceuticals· 0 citations
This review summarizes emerging therapeutic strategies for EOC, their mechanisms of action, and their potential to overcome treatment resistance, and covers molecularly targeted therapies, immunotherapies, metabolic and epigenetic approaches, cellular and gene therapies, targeted drug-delivery systems, and locoregional and physical modalities.
Zofia Pietrasik, Mikołaj Kapała, Joanna Pietrasik et al.· Cancers· 0 citations
Gynecological cancers (GCs) remain a leading cause of cancer-related mortality among women worldwide. Their high mortality rate is strongly linked to resistance to chemotherapy and targeted therapy, which significantly affects treatment efficacy and patient survival. This review summarizes the status of drug resistance in ovarian cancer (OC), cervical cancer (CC), and endometrial cancer (EC), and elucidates their multi-level drug resistance mechanisms in five aspects: DNA damage repair (DDR) dysregulation, core signaling pathways dysregulation, epigenetic dysregulation, transmembrane drug transport dysregulation, and tumor microenvironment (TME) dysregulation. Based on these mechanisms, this review synthesizes six corresponding reversal strategies: DDR inhibition, core signaling pathway intervention, epigenetic regulation, drug transport protein regulation, tumor microenvironment (TME) interventions, and emerging technologies applications. The evidence discussed ranges from preclinical studies to clinical trials. By integrating key findings on the multifaceted mechanisms of drug resistance and associated reversal approaches in GCs, this review also discusses the limitations of current therapies and provides perspectives for further mechanistic investigation and the development of novel treatment strategies.
Tiange Xing, Hongxi Liu, Wen-Jing Yu et al.· Journal of Visualized Experi...· 0 citations
Breast cancer is the most frequently reported cancer in women, with high mortality and morbidity globally. Paclitaxel, doxorubicin, tamoxifen, cisplatin, and 5-fluorouracil are cornerstones of standard-of-care treatment for primary and advanced breast cancers, targeting distinct molecular mechanisms. However, the evolution of acquired resistance primarily leads to treatment failure and progression to metastasis, ultimately to patient mortality. Furthermore, their effectiveness is limited by potential toxicities in various organs. These limitations present an extreme challenge for the management of breast cancer at the advanced stage. This review uncovers recent updates on acquired resistance mechanisms toward standard-of-care treatments driven by deeply rooted heterogeneity and aggressive nature through direct counteracting of its core action, hyperactivation of survival pathways, silencing of core cell death pathways, derepressing the expression of multidrug resistance proteins, metabolic reprogramming, epigenetic modifications, and exosome-mediated horizontal transfer of resistance phenotype. In addition, we discuss recent updates on potential strategies to overcome resistance and toxicities induced by standard-of-care treatments. Ultimately, this review helps to identify novel strategies targeting pathways to reverse resistance and reduce toxicity in breast cancer patients.
Anuveda Sree Samudrala, G. P. Nagaraju, RamaRao Malla· Biochimica et biophysica act...· 0 citations
