Adenocarcinomas of the Lung and Neurotrophin System: A Review

Abstract

Neurotrophins (NTs) represent a group of growth factors with pleiotropic activities at the central nervous system level. The prototype of these molecules is represented by the nerve growth factor (NGF), but other factors with similar functions have been identified, including the brain derived-growth factor (BDNF), the neurotrophin 3 (NT-3), and NT 4/5. These growth factors act by binding specific low (P75) and high-affinity tyrosine kinase (TrkA, B, and C) receptors. More recently, these growth factors have shown effects outside the nervous system in different organs, particularly in the lungs. These molecules are involved in the natural development of the lungs, and their homeostasis. However, they are also important in different pathological conditions, including lung cancer. The involvement of neurotrophins in lung cancer has been detailed most for non-small cell lung cancer (NSCLC), in particular adenocarcinoma. This review aimed to extensively analyze the current knowledge of NTs and lung cancer and clarify novel molecular mechanisms for diagnostic and therapeutic purposes. Several clinical trials on humans are ongoing using NT receptor antagonists in different cancer cell types for further therapeutic applications. The pharmacological intervention against NT signaling may be essential to directly counteract cancer cell biology, and also indirectly modulate it in an inhibitory way by affecting neurogenesis and/or angiogenesis with potential impacts on tumor growth and progression.

Targeted Molecular Profiling of Non-small Cell Lung Cancer in India

“…Raising awareness about this biomarker is crucial to employing a therapeutic approach that is highly effective and well-tolerated in treating both common cancers like NSCLC, where extensive tumor genotyping has become clinical practice, and rare tumors, where NTRK rearrangements are pathognomonic (80). Compared to other histological types, especially adenocarcinoma, NTRK1 and NTRK2 are more frequently expressed in epidermoid carcinoma (81). In a cohort of 686 individuals with epidermoid carcinoma, NTRK1 showed high specificity (92.8%) but mediocre sensitivity (71.6%).…”

Targeting nerve growth factor-mediated osteosarcoma metastasis: mechanistic insights and therapeutic opportunities using larotrectinib

“…Researchers have demonstrated that inhibiting NGF or its receptor (TrkA) significantly retards tumor development, reduces pain-related activity, and ameliorated bone damage in sarcoma. The NGF/TrkA axis has also been implicated in the metastasis of various tumors, including breast cancer [22], lung cancer [23], colon cancer [24], pancreatic cancer [25], and prostate cancer [20]. In recent years, medicinal chemists have made considerable advances in our understanding of TRK inhibitors.…”

Nerve Growth Factor and the Role of Inflammation in Tumor Development

“…Inflammation, as stated before, is a complex biological response triggered by the body's immune system to protect against harmful stimuli, such as tissue damage and pathogens. In this scenario, NGF can regulate the innervation and neuronal activity of peripheral neurons, inducing the release of immuneactive cytokines, neuropeptides, and neurotransmitters [14,[187][188][189]. Furthermore, NGF can also directly influence innate and adaptive immune responses through its interaction with various cells involved in the immune response, including mast cells, lymphocytes, and macrophages [28,190].…”