Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations

Abstract

The success of antibodies targeting Programmed cell death protein 1 (PD-1) and its ligand L1 (PD-L1) in cancer treatment and the need for improving response rates has led to an increased demand for the development of combination therapies with anti-PD-1/PD-L1 blockers as a backbone. As more and more drugs with translational potential are identified, the number of clinical trials evaluating combinations has increased considerably and the demand to prioritize combinations having potential for success over the ones that are unlikely to be successful is rising. This review aims to address the unmet need to prioritize cancer immunotherapy combinations through comprehensive search of potential drugs and ranking them based on their mechanism of action, clinical efficacy and safety. As lung cancer is one of the most frequently studied cancer types, combinations that showed potential for the treatment of lung cancer were prioritized. A literature search was performed to identify drugs with potential in combination with PD-1/PD-L1 blockers and the drugs were ranked based on their mechanism of action and known clinical efficacy. Nineteen drugs or drug classes were identified from an internal list of lead molecules and were scored for their clinical potential. Efficacy and safety data from pivotal studies was summarized for the selected drugs. Further, overlap of mechanisms of action and adverse events was visualized using a heat map illustration to help screen drugs for combinations. The quantitative scoring methodology provided in this review could serve as a template for preliminary ranking of novel combinations.

Clinical Efficacy and Psychological Impact of Omaha-Based Continuing Care for Prostate Cancer Patients

“…This study shows that Omaha system application in patients' postoperative continuation care plays an important role in improving self-care ability, helps patients treat their own conditions correctly, and enhances patients' sense of self-efficacy. Analyze the reason: Omaha system model nursing can increase patients' understanding of diseaserelated knowledge, correct misunderstandings in time, help patients master professional nursing knowledge, improve self-care ability, and ensure the smooth implementation of various nursing tasks [32][33][34]. At the same time, it alleviates patients' worries, enhances patients' confidence in overcoming the disease, enables patients to maintain a positive attitude towards their own diseases, and obtains ideal care effects [35].…”

Linear DNA amplicons as a novel cancer vaccine strategy

“…It has been already shown elsewhere that neoantigen-based DNA vaccine approach is a potential alternative to currently established cancer immunotherapies, especially when administered as cotreatment with immune checkpoint inhibitors [ 5 ]. Indeed, the combination of ICIs with a vaccine therapy has already proven to be effective in eliciting an antitumoral response both in preclinical models and in human clinical studies [ 35 , 36 ]. Furthermore, the combination of different therapeutic strategies (i.e.…”

Prediction of Early Response to Immunotherapy: DCE-US as a New Biomarker

“…This result seems to be consistent with the changes in the tissue level induced by the introduction of ICIs. Immune checkpoint blocking is shown to activate and lead to the proliferation of T-cells and NK-cells [ 15 , 19 ]. A pro-inflammatory environment is created.…”