The treatment of many solid tumours has been revolutionized by immune checkpoint inhibitors (ICIs), although clinical results are still quite erratic and unexpected. The intricate biology that controls treatment outcomes is not captured by conventional biomarkers like PD-L1 expression, tumour mutational burden, and microsatellite instability, which offer limited predictive accuracy. A growing body of research indicates that the tumour immune microenvironment (TME), which reflects dynamic interactions between immune cells, stromal elements, cytokine networks, metabolic signals, and tumour-intrinsic pathways, is crucial in determining responsiveness or resistance to ICIs. A deeper understanding of these interactions has been made possible by advances in multi-omic technologies, such as genomics, transcriptomics, epigenomics, proteomics, metabolomics, spatial profiling, and single-cell analyses. These technologies have also identified important immune-microenvironment signatures linked to therapeutic success or failure. Clinical results are influenced by several TME immunophenotypes, T-cell activation and exhaustion stages, antigen-presentation ability, myeloid-derived suppression, stromal barriers, metabolic reprogramming, and interferon signaling. The development of composite biomarkers that provide more precise and biologically based prediction of ICI response is currently supported by emerging multi-omic and spatial techniques. This review highlights the fundamental processes of primary and acquired resistance, summarizes the current understanding of multi-omic immune-microenvironment signatures across major solid tumours, and addresses recent translational developments that are propelling the next generation of predictive biomarkers. This review proposes a framework for improving patient stratification and informing precision immunotherapy across diverse solid tumour contexts by integrating mechanistic insights with emerging technological platforms.
S. A. Fasogbon, Iniobong Anselem Udo, Kevin Odega et al.· Discover Oncology· 0 citations
Breast cancer remains a leading cause of mortality among women globally, underscoring the urgent need for novel therapies that combine high efficacy with minimal adverse effects. This study examines the bioinformatic design of animal-derived therapeutic peptides targeting two key breast cancer biomarkers: matrix metalloproteinase 1 (MMP1) and epidermal growth factor receptor (EGFR). Approximately 1,500 antimicrobial peptides were retrieved from the antimicrobial peptide database 3 (APD3). They were screened for hemolytic properties using the Hemolytik database. This screening resulted in 255 non-hemolytic candidates, which were further screened through VaxiJen 2.0 and ToxinPred2 for antigenicity and allergenicity. Moreover, physicochemical properties were analyzed using the Expasy ProtParam server. We applied thresholds of molecular weight (1.7–3.1 kDa), instability index (≤ 28), and net charge (+ 2 to + 7). Five peptides met all criteria and were screened for anticancer potential using AntiCP 2.0 and ACPred, identifying three overlapping anticancer peptides (ACPs), including Metalnikowin IIA (AP00363) from Palomena prasina, Guentherin (AP00584) from Hylarana guentheri, and P-10 (AP02393) from Ciona intestinalis. Furthermore, peptide structures were modeled using Colab AlphaFold2. Tertiary structures of target proteins were obtained from UniProt, and Buserelin (FDA-approved ACP) was obtained from the DCTPep database. All peptides were docked against MMP1 and EGFR using HDock and ClusPro. AP00363 showed the highest docking affinity with MMP1 and EGFR, scoring −235.61 and −271.70, respectively. Molecular dynamics simulations supported the stability and interaction potential of these peptides. Overall, this study presents promising bioinformatically designed, animal-derived ACPs for targeted breast cancer therapy. Further in vitro and in vivo validation is necessary to assess clinical relevance.
E. K. Oladipo, Omolara Omoboye Adegboye, S. F. Adeyemo et al.· Future Journal of Pharmaceut...· 0 citations
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