The new era of lung cancer therapy: Combining immunotherapy with ferroptosis.

Ferroptosis is an unconventional programmed cell death mode caused by phospholipid peroxidation dependent on iron. Emerging immunotherapies (especially immune checkpoint inhibitors) have the potential to enhance lung cancer patients' long-term survival. Although immunotherapy has yielded significant positive applications in some patients, there are still many mechanisms that can cause lung cancer cells to evade immunity, thus leading to the failure of targeted therapies. Immune-tolerant cancer cells are insensitive to conventional death pathways such as apoptosis and necrosis, whereas mesenchymal and metastasis-prone cancer cells are particularly vulnerable to ferroptosis, which plays a vital role in mediating immune tolerance resistance by tumors and immune cells. As a result, triggering lung cancer cell ferroptosis holds significant therapeutic potential for drug-resistant malignancies. Here, we summarize the mechanisms underlying the suppression of ferroptosis in lung cancer, highlight its function in the lung cancer immune microenvironment, and propose possible therapeutic strategies.

Nrf2--a hidden bridge linking cancer stem cells to ferroptosis.

Cancer stem cells (CSCs), a small population of stem cells existing in cancer cells, are considered as the "culprits" of tumor recurrence, metastasis, and drug resistance. Ferroptosis is a promising new lead in anti-cancer therapy. Because of unique metabolic characteristics, CSCs' growth is more dependent on the iron and lipid than ordinary cancer cells. When the metabolism of iron/lipid is disordered, that is, imbalanced redox homeostasis, CSCs are more susceptible to ferroptosis. The expression of Nuclear factor E2-related factor 2 (Nrf2), a molecule playing a major regulatory role in redox homeostasis, determines whether the cells are under oxidative stress and ferroptosis occurs. Nrf2 expression level is higher in CSCs, indicating stronger dependence on Nrf2. Here we expound the unique biological and metabolic characteristics of CSCs, explore the mechanism of inducing ferroptosis by targeting Nrf2, thus providing promising new targets for eliminating aggressive tumors and achieving the goal of curing tumors.

Immune checkpoint inhibitors as a threat to reproductive function: A systematic review.

In recent years, the indications for immunotherapy in cancer treatment have been expanding. The increased risk of cancer in young people, coupled with the fact that many women or men choose to delay childbearing, has made an increasing number of patients of childbearing age eligible for immunotherapy. Furthermore, with the improvements of various treatments, more young people and children are able to survive cancer. As a result, long-term sequelae of cancer treatments, such as reproductive dysfunction, are increasingly important for survivors. While many anti-cancer drugs are known to cause reproduction dysfunction, the effects of immune checkpoint inhibitors (ICIs) on reproduction function remain largely unknown. Through a retrospective analysis of previous reports and literature, this article aims to elucidate the causes of reproductive dysfunction induced by ICIs and focus on their specific mechanisms, in order to providing some guidance to clinicians and patients.

Ferroptosis: Reviewing CRC with the Third Eye.

Colorectal cancer (CRC) has been one of the most common cancers and maintains the second-highest incidence and mortality rates among all cancers. The high risk of recurrence and metastasis and poor survival are still huge challenges in CRC therapy, in which the discovery of ferroptosis provides a novel perspective. It has been ten years since a unique type of regulated cell death driven by iron accumulation and lipid peroxidation was proposed and named ferroptosis. During the past decade, there have been multiple pieces of evidence suggesting that ferroptosis participates in the pathophysiological processes during disease progression. In this review, we describe ferroptosis as an imbalance of oxidant systems and anti-oxidants which results in lipid peroxidation, membrane damage, and finally cell death. We elaborate on the mechanisms of ferroptosis and systematically summarize recent studies on the regulatory pathways of ferroptosis in CRC from various perspectives, ranging from encoding genes, noncoding RNAs to regulatory proteins. Finally, we discuss the potential therapeutic role of ferroptosis in CRC treatments.