Targeted Therapies: Immunologic Effects and Potential Applications Outside of Cancer

Abstract

Two pharmacologic approaches that are currently at the forefront of treating advanced cancer are those that center on disrupting critical growth/survival signaling pathways within tumor cells (commonly referred to as "targeted therapies") and those that center on enhancing the capacity of a patient's immune system to mount an antitumor response (immunotherapy). Maximizing responses to both of these approaches requires an understanding of the oncogenic events present in a given patient's tumor and the nature of the tumor-immune microenvironment. Although these 2 modalities were developed and initially used independently, combination regimens are now being tested in clinical trials, underscoring the need to understand how targeted therapies influence immunologic events. Translational studies and preclinical models have demonstrated that targeted therapies can influence immune cell trafficking, the production of and response to chemokines and cytokines, antigen presentation, and other processes relevant to antitumor immunity and immune homeostasis. Moreover, because these and other effects of targeted therapies occur in nonmalignant cells, targeted therapies are being evaluated for use in applications outside of oncology.

Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning

“…At the same time, stromal immune cells contribute to a variety of diseases ranging from diabetes to artherosclerosis, fibrosis, cancer and neurodegeneration (Wynn et al, 2013 ). While targeting stromal immune cells is a promising strategy for the development of novel therapeutics for a wide range of diseases (Kersh et al, 2018 ) and recently has gained wide attention in cancer drug discovery and for the therapy of neurological diseases (Villoslada et al, 2008 ; Pitt et al, 2016 ; Alsaab et al, 2017 ; Chitnis and Weiner, 2017 ; Kabba et al, 2017 ; Pogge von Strandmann et al, 2017 ), immune cells also modulate therapeutic response to drugs not directly targeting the immune system (Kersh et al, 2018 ). In drug discovery, in vitro modeling of such complex interactions will require multicellular 3D tissue models with organoids currently being at the forefront for disease modeling, drug screening and drug development.…”

Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review

“…Moreover, immune‐related pathways, such as those of IFN‐α and IFN‐β, were reported to be enriched in CDK4/6 inhibitor‐resistant breast cancer cells . In one preclinical study, CDK4/6 inhibitors were reported to promote anti‐tumor immunity, similar to other targeted therapies …”

“…89 In one preclinical study, CDK4/6 inhibitors were reported to promote anti-tumor immunity, 103 similar to other targeted therapies. 104 . Mechanistically, CDK4/6 inhibitors reduced the activity of DNA methyltransferase, an E2F target protein which promotes cytotoxic T cell-mediated tumor inhibition.…”

COVID-19 vaccines for patients with cancer: benefits likely outweigh risks

“…Targeted therapies include receptor tyrosine kinase inhibitors (TKIs) such as erlotinib, sunitinib, and imatinib or monoclonal antibodies such as trastuzumab. Targeted therapies should not directly cause immunosuppression as part of their mechanism of action, but may have unintended inhibitory effects on antigen presenting cell function, T cell activation [ 67 ] and B cell signaling [ 68 ]. Nevertheless, patients treated with sunitinib or sorafenib develop seroprotection with the influenza vaccine comparable to healthy controls [ 69 ].…”