Academia oncology最新文献

Autophagy is an evolutionarily conserved catabolic process that enables cells to degrade and recycle long-lived proteins and damaged organelles, playing an important role in cellular homeostasis and survival under stress. In lung cancer, autophagy has emerged as a key modulator of tumour cell survival and is a significant factor influencing chemotherapy efficacy. However, the contribution of autophagy to chemoresistance remains complex and incompletely understood. Recent studies identify microRNA (miRNAs), a class of small non-coding RNAs, as critical regulators of autophagy, capable of modulating autophagy-related genes and signalling pathways. Through this regulatory capacity, miRNAs can alter autophagic activity in lung cancer cells, thereby influencing both chemosensitivity and the development of chemoresistance. This review summarises current advances in the understanding of the miRNA-mediated regulation of autophagy in the context of lung cancer, with particular emphasis on its impact on chemotherapy response. Mechanistic insights into how miRNAs govern specific stages of the autophagic process are examined, and the potential for therapeutic intervention targeting the miRNA-autophagy axis to mitigate chemoresistance in lung cancer is discussed.

We investigated the growth-inhibitory activity of the pan-AKT inhibitor ipatasertib in combination with other targeted therapies. Thirty-nine patient-derived cancer cell lines from the NCI Patient-Derived Models Repository and nine NCI-60 tumor cell lines were grown as mct-spheroids. The mct-spheroids, a mixture of tumor cells (60%), endothelial cells (25%), and mesenchymal stem cells (15%), were established for 3 days before compounds(s) were added. All agents were tested at concentrations up to the reported clinical C_max values or a high concentration of 10 μM. Cell viability was assayed using CellTiter-Glo 3D after 7 days of exposure. Ipatasertib was selective for tumor cells harboring activating PI3K/AKT/mTOR pathway mutations. Dual inhibition of the PI3K/AKT/mTOR and RAS/MEK/ERK pathways was very effective. The combination of ipatasertib with the MEK inhibitor selumetinib or the ERK inhibitor ravoxertinib resulted in additive and/or greater-than-additive cytotoxicity in approximately half the cell lines screened. The V600E mutation-specific BRAF inhibitor vemurafenib and the KRAS G12C selective inhibitor sotorasib in combination with ipatasertib were active in the eight BRAF V600E and four KRAS G12C mutant-containing cell lines, respectively. Vertical inhibition of the PI3K/AKT/mTOR pathway with the mTORC1/2 kinase inhibitor sapanisertib demonstrated additive and/or greater-than-additive effects in multiple cell lines. In early experiments, there was a correlation between the response to ipatasertib and selumetinib in two patient-derived tumor lines grown as mct-spheroids and the corresponding patient-derived xenografts. All data are accessible via the PubChem BioAssay public database.

Ovarian cancer is the seventh most common cancer in women and the eighth most common cause of cancer death worldwide. It is an aggressive disease with five-year survival rates below 45% and many patients relapse within 2 years. Further treatments become more intense, resulting in chemotherapy drug resistance and increased toxicity. This has created the need to develop new therapeutic strategies to improve the quality of life and treatment options for ovarian cancer patients. Studies have reported the role of cysteine in ovarian cancer, primarily as a precursor of glutathione (GSH), contributing to the endogenous antioxidant mechanism. The membrane-permeable cysteine precursor N-acetylcysteine (NAC) can enhance the intracellular cysteine pool and thus results in decreased oxidative stress. This characteristic provides NAC with a rationale as a potentially effective chemo-protectant in ovarian cancer treatment. In this review, we summarize the effects of NAC supplementation in ovarian cancer from recent preclinical studies. The role of NAC in chemotherapy response, and mechanisms to overcome chemo resistance in ovarian cancer (including targeting the Mirk/dyrk1B kinase pathway) are also explored. While NAC holds therapeutic promise in alleviating treatment-associated toxicities, its application in ovarian cancer requires careful consideration based on tumour subtype, redox context, and treatment timing. Future research incorporating subtype-specific models and clinical trials will be essential to delineate the precise role of NAC and optimize its integration into ovarian cancer treatment regimens.

Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck. Stagnating survival rates in recent decades, despite advances in the treatment paradigms, surveillance technologies, and multidisciplinary care, leave clinicians with a need for better options for screening, risk-stratifying, and monitoring patients. A growing proportion of patients with HPV-associated SCC have improved outcomes but continue to have a heterogenous response to treatment. Advances in the platforms and assays measuring circulating tumor DNA offer an opportunity to monitor disease status at the molecular level for both virally mediated and traditional risk-factor-driven SCC of the head and neck. This overview will discuss experimental, clinically used, and commercially available liquid biopsy platforms and their recent applications in patients with head and neck SCC malignancies.