Molecular Pathways: The Balance between Cancer and the Immune System Challenges the Therapeutic Specificity of Targeting Nuclear Factor-κB Signaling for Cancer Treatment

Abstract

The Nuclear Factor-κB (NF-κB) signaling pathway is a complex network linking extracellular stimuli to cell survival and proliferation. Cytoplasmic signaling to activate NF-kB can occur as part of the DNA damage response or in response to a large variety of activators including viruses, inflammation, and cell death. NF-κB transcription factors play a fundamental role in tumorigenesis and are implicated in the origination and propagation of both hematologic and solid tumor types, including melanoma, breast, prostate, ovarian, pancreatic, colon, lung, and thyroid cancers. On the other hand, NF-kB signaling is key to immune function, and is likely necessary for anti-tumor immunity. This presents a dilemma when designing therapeutic approaches to target NF-kB. There is growing interest in identifying novel modulators to inhibit NF-κB activity since impeding different steps of the NF-κB pathway has potential to slow tumor growth, progression, and resistance to chemotherapy. Despite significant advances in our understanding of this pathway, our ability to effectively clinically block key targets for cancer therapy remains limited due to on-target effects in normal tissues. Tumor specificity is critical to developing therapeutic strategies targeting this anti-apoptotic signaling pathway in order to maintain anti-tumor immune surveillance when applying such therapy to patients.

Supramolecular Nanofibers of Curcumin for Highly Amplified Radiosensitization of Colorectal Cancers to Ionizing Radiation

“…To elucidate the molecular mechanisms of such radiosensitization by Cur‐SNFs and to compare the mechanisms with free curcumin, we evaluated a panel of significant downstream targets of curcumin. A prominent driver of treatment resistance in cancer is the nuclear factor kappa B (NF‐κB) pathway . NF‐κB is constitutively activated in many cancers and can exert several protumorigenic functions.…”

Knockdown of ectodysplasin‑A receptor‑associated adaptor protein exerts a tumor‑suppressive effect in tongue squamous cell carcinoma cells

“…Moreover, deviated activation of the NF-κB signaling is associated with the propagation of many cancers (48,49). NF-κB has a dual role in cancer, it not only participates in the immune defense, which can target and eliminate transformed cells, but is also activated in many types of cancer, contributing to the dysregulation of gene expression and prevention of apoptosis and hence, it is responsible for various tumor-promoting functions (50,51).…”

Ping-Pong—Tumor and Host in Pancreatic Cancer Progression

“…The dectin1-galectin9 axis is central in directing the differentiation of TAM to a M2like phenotype, which suffices for reprogramming CD4+ and CD8+ T-cells (749). Finally, we list some reviews helpful as starting information on PaCa-selective metabolic changes that affect immune responses in PaCa (739,(750)(751)(752)(753)(754).…”