CXCR4 Based Therapeutics for Non-Small Cell Lung Cancer (NSCLC)

Abstract

Lung cancer is the second most common malignancy. Unfortunately, despite advances in multimodality therapeutics for the disease, the overall five-year survival rate among newly diagnosed lung cancer patients remains in the range region of 15%. In addition, although immune checkpoint inhibitors are increasingly being incorporated into lung cancer treatment protocols, the proportion of patients that respond to these agents remains low and the duration of response is often short. Therefore, novel methodologies to enhance the efficacy of immunotherapy in lung cancer are highly desirable. Chemokines are small chemotactic cytokines that interact with their 7 transmembrane G-protein–coupled receptors, to guide immune cell trafficking in the body under both physiologic and pathologic conditions. Tumor cells highjack a small repertoire of the chemokine/chemokine receptor system and utilize it in a manner that benefits local tumor growth and distant spread. The chemokine receptor, CXCR4 is expressed in over 30 types of malignant tumors and, through interaction with its ligand CXCL12, was shown exert pleotropic pro-tumorigenic effects. In this review, the pathologic roles that CXCL12/CXCR4 play in lung cancer propagation are presented. Furthermore, the challenges and potential benefits of incorporating drugs that target CXCL12/CXCR4 into immune-based lung cancer therapeutic protocols are discussed.

A new role for circulating T follicular helper cells in humoral response to anti-PD-1 therapy

“… 30 31 54 Hence, it would be of great interest to evaluate the precise role of CXCL13 in tumor development in our model, and the actual effect of anti-PD-1 therapy on CXCL13 expression in human NSCLC. Similarly, CXCL12 is known to exert protumorigenic and prometastatic actions in NSCLC, 55 which could be partially counteracted by the decreased production of this chemokine on anti-PD-1 treatment ( online supplemental figure 3B ). Finally, CD103+ DC-derived CXCL9 has been proposed to mediate response to anti-PD-1 therapy in a murine model of colon cancer by facilitating DC-T cell interactions.…”

Role of Chemokines in the Biology of Cholangiocarcinoma

“…Upregulation of CXCR4 expression has been observed in different human cancers [ 104 ], and the CXCL12/CXCR4 axis is often considered a hallmark of cancer aggressiveness and correlates with tumor size, grade and recurrence [ 105 , 106 , 107 , 108 ], poor prognosis [ 106 ] and low survival [ 109 ]. In some tumors, it is also critical for drug-resistance [ 110 , 111 ].…”

Effect of Wenxia Changfu Formula Combined With Cisplatin Reversing Non-Small Cell Lung Cancer Cell Adhesion-Mediated Drug Resistance

“…NSCLC is epithelium-derived lung cancer including adenocarcinoma and squamous carcinomas and large cell carcinoma, accounting for nearly 80% of all newly diagnosed lung cancer cases (Wald, 2018).…”

“…NSCLC is epithelium-derived lung cancer including adenocarcinoma and squamous carcinomas and large cell carcinoma, accounting for nearly 80% of all newly diagnosed lung cancer cases ( Wald, 2018 ). The first-line chemotherapeutic agents for the treatment of human NSCLC is chemotherapy based on platinum drugs ( Quarta et al., 2019 ).…”