FAT4 may enhance ferroptosis sensitivity in HCC by suppressing GPX4 and SLC7A11 expression, potentially by inhibiting PI3K/AKT signaling. Thus, this study presents FAT4 as a biomarker associated with tumor progression and a potential determinant for overcoming ferroptosis resistance in HCC.

Selenoenzyme glutathione peroxidase 4 (GPX4) controls this process by reducing lipid peroxides and can be pharmacologically inhibited by agents such as RSL3 and JKE1674...However, by assessing expression of iron regulatory genes as well as employing two orthogonal approaches to measure labile iron, we found that the LIP did not measurably increase during ferroptosis induction with GPX4 or SLC7A11 inhibition. These findings suggest that the LIP does not expand upon pharmacologically initiated ferroptosis, despite the potentiating effect of exogenous iron supplementation.

In vivo, NSUN2 depletion potentiated the antitumor activity of OXA in SW480 xenografts, and combining OXA with the ferroptosis inducer imidazole ketone erastin (IKE) further reduced tumor burden compared with OXA alone, accompanied by increased tumor MDA levels. DHODH restoration rescued ferroptosis and reversed the enhanced drug sensitivity induced by NSUN2 knockdown. These findings identify an NSUN2-DHODH epitranscriptomic axis that promotes CRC progression and OXA resistance by limiting ferroptosis, supporting NSUN2-targeting and ferroptosis-inducing strategies to improve chemotherapy response.

Gomisin B inhibited the transcriptional activation of USP7 by downregulating ESR1, thereby suppressing the deubiquitination of SREBF1. This enhanced NB ferroptosis to alleviate NB progression.

NFIB knockout enhances erastin-induced ferroptosis, marked by elevated Fe2 +, MDA, and ROS levels...In vivo, combined NFIB suppression and ferroptosis induction significantly inhibit tumor growth and increase lipid peroxidation in CRPC xenografts. These findings uncover a critical role of NFIB phase separation and acetylation in ferroptosis regulation and suggest NFIB as a promising therapeutic target in CRPC.

PTX sensitivity was tested in vitro and in xenografts, with or without the ferroptosis inducer RSL3. ANO6 confers PTX resistance by sustaining GPX4-dependent ferroptosis evasion and mitochondrial homeostasis. Targeting the ANO-GPX4 axis, alone or combined with ferroptosis induction, may improve chemotherapy sensitivity in cervical cancer.

Collectively, these findings establish SLC3A2 as playing a vital oncogenic role in BC tumorigenesis and progression. Its function in inhibiting ferroptosis-especially during cisplatin-based chemotherapy-makes it a promising therapeutic target.

In vitro, ferroptosis was induced in an L929-HaCaT co-culture system using erastin/RSL3, and cells were treated with various concentrations of Rb1. Rb1 functions as an SIRT1-AMPK activator that inhibits ferroptosis and inflammation to promote PI wound healing. These findings underpin the efficacy of Rb1 as a promising multi-target therapeutic candidate for future clinical development.

In vitro, DPP4 overexpression in PDAC cell lines inhibited cell proliferation, induced G1-S cell cycle arrest, impaired mitochondrial respiration, and markedly sensitized cells to erastin-induced ferroptosis...ACSL4 knockdown rescued DPP4 overexpression-induced ferroptosis and lipid ROS accumulation. These results demonstrate that DPP4 acts as a positive regulator of ferroptosis in PDAC by stabilizing ACSL4, highlighting the DPP4-ACSL4 axis as a potential therapeutic target to enhance ferroptosis-based strategies against this aggressive cancer.

LDHB-K58 delactylation drives gastric cancer metastasis via SLC7A11-mediated GSH synthesis and ferroptosis resistance, suggesting therapeutic targeting of this axis for overcoming therapy resistance.

ME could target OTUD4 to stabilize the core ferroptosis defense factor GPX4 and activate NRF2/GPX4 signaling pathway as a novel ferroptosis inhibitor to alleviate UC. These findings could suggest ME to be a promising lead compound for further modification and highlight OTUD4 as a potential new target for anti-inflammatory drug development.

On the other hand, ferroptosis inducers such as erastin and RSL3 have the potential to overcome apoptotic resistance and avoid efflux pathways, which recover therapeutic efficacy. We also review recent data on the complex interactions between resistance to chemotherapy and ferroptosis, and outline approaches that may stimulate iron accumulation to reverse MDR. By emphasizing novel methods to induce ferroptosis, this review highlights that this approach is a promising strategy to overcome chemotherapy resistance in colon cancer and will facilitate the development of more precise and efficient treatment.