Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer‐related death worldwide. A first‐line standard of care (SoC), sorafenib results in median overall survival (OS) of 12 months in Child‐Pugh class A patients, and 6 months in Child‐Pugh class B patients with objective response rates (ORR) not exceeding 19%. These low efficacy rates have driven research on alternative therapeutic options, particularly immune‐checkpoint inhibitors (ICIs). We reviewed the response rates (estimated by RECIST 1.1 criteria) across patients with advanced HCC treated with ICIs in phase I‐IV clinical trials published between December 2012 to December 2020; 17 reports were identified as eligible and included in the quantitative analysis. Within the selected studies pembrolizumab + lenvatinib reached the highest absolute ORR (36%), with first line atezolizumab + bevacizumab showing the second highest ORR (27.3%). With regards to second line therapy nivolumab + ipilimumab reached an ORR of 32% and pembrolizumab alone resulted in an ORR of 17% among sorafenib‐experienced patients with advanced HCC. In summary, current studies show high response rates of ICIs in patients with advanced HCC. Nonetheless, further studies are required in the second‐line setting to further evaluate ICI therapeutic superiority. Finally, it is of particular interest to examine the therapeutic potential of ICIs for patients with decompensated liver disease (Child‐Pugh class C), currently not eligible for any systemic therapy. Implications for practice Immune‐checkpoint inhibitors (ICIs) can provide high objective response rates (estimated with RECIST 1.1. criteria) when used as first‐line treatment in advanced hepatocellular carcinoma, particularly: pembrolizumab + lenvatinib (ORR 36%) or atezolizumab + bevacizumab (ORR 27.3%). In sorafenib‐experienced patients, nivolumab + ipilimumab (ORR 32%) provided the highest ORR among ICI‐based regimens. Our findings emphasize high therapeutic potential of ICI‐based therapies in patients with advanced hepatocellular carcinoma, though further studies are required to further validate and define their role in this context.

Background. Colorectal cancer (CRC) is the fourth most deadly cancer worldwide. Unfortunately, a quarter of the patients are diagnosed at late stages, when surgical options are limited. Targeted therapies, particularly immune-checkpoint inhibitors (ICIs), are the latest addition and have been studied herein regarding their efficacy outcomes. Methods. Clinical studies were identified through the PubMed, Scopus and Cochrane databases. Any trial that evaluated ICIs in patients with metastatic CRC (mCRC) and reported the objective response rate was deemed eligible. Data analysis was performed by employing the random-effects model in STATA v.17. Results. A total of 461 articles were identified; 13 clinical trials were included, encompassing a total cohort of 1209 patients. Our study determined that a single PD-1/PD-L1 checkpoint blockade provides durable clinical response in mCRC patients with high microsatellite instability (MSI-H). The combinatorial therapy of CTLA-4 + PD-1 inhibitors also showed high response rates in pre-treated MSI-H patients. The single-arm REGONIVO trial reported durable clinical response in patients with microsatellite stable (MSS) status. Conclusions. Our study surmises that PD-1/PD-L1 inhibitors as well as combination therapy with CTLA-4 and PD-1 inhibitors show encouraging response rates in mCRC patients, albeit exclusively in patients with cancer that are of MSI-H status. A single study suggests that nivolumab + regorafenib can reach a durable response rate in MSS patients; however, further studies in larger randomized settings are required.

Non-coding RNAs (ncRNAs) are an abundant component of the human transcriptome. Their biological role, however, remains incompletely understood. Nevertheless, ncRNAs are highly associated with cance...

Cancer Drug Resistance is an open access journal, focusing on pharmacological aspects of drug resistance and its reversal, molecular mechanisms of drug resistance and drug classes, etc. Both clinical and experimental aspects of drug resistance in cancer are included.

Increasing evidence strongly supports the key role of the tumour microenvironment in response to systemic therapy, particularly immune checkpoint inhibitors (ICIs). The tumour microenvironment is a complex tapestry of immune cells, some of which can suppress T-cell immunity to negatively impact ICI therapy. The immune component of the tumour microenvironment, although poorly understood, has the potential to reveal novel insights that can impact the efficacy and safety of ICI therapy. Successful identification and validation of these factors using cutting-edge spatial and single-cell technologies may enable the development of broad acting adjunct therapies as well as personalised cancer immunotherapies in the near future. In this paper we describe a protocol built upon Visium (10x Genomics) spatial transcriptomics to map and characterise the tumour-infiltrating immune microenvironment in malignant pleural mesothelioma. Using ImSig tumour-specific immune cell gene signatures and BayesSpace Bayesian statistical methodology, we were able to significantly improve immune cell identification and spatial resolution, respectively, improving our ability to analyse immune cell interactions within the tumour microenvironment.