The field of research in bladder cancer has seen significant advances in recent years. Next-generation sequencing has identified the genes most mutated in bladder cancer. This wealth of information allowed the definition of driver mutations, and identification of actionable therapeutic targets, as well as a clearer picture of patient prognosis and therapeutic direction. In a similar vein, our understanding of the cellular aspects of bladder cancer has grown. The identification of the cellular geography and the populations of different cell types and quantifications of normal and abnormal cell types in tumours provide a better prediction of therapeutic response. Non-invasive methods of diagnosis, including liquid biopsies, have seen major advances as well. These methods will likely find considerable utility in assessing minimal residual disease following treatment and for early-stage diagnosis. A significant therapeutic impact on patients with bladder cancer is found in the use of immune checkpoint inhibitor therapeutics. These therapeutics have been shown to cure some patients with bladder cancer and significantly decrease adverse events. These developments provide patients with better monitoring opportunities, unique therapeutic options and greater hope for prolonged survival. This Review examines recent developments in the molecular and translational aspects of bladder cancer biology and discusses their current or potential future clinical applications in the management of bladder cancer.

Advances in bladder cancer biology and therapy

Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set.

Exosomes, a nano-sized subtype of extracellular vesicles secreted from almost all living cells, are capable of transferring cell-specific constituents of the source cell to the recipient cell. Cumulative evidence has revealed exosomes play an irreplaceable role in prognostic, diagnostic, and even therapeutic aspects. A method that can efficiently provide intact and pure exosomes samples is the first step to both exosome-based liquid biopsies and therapeutics. Unfortunately, common exosomal separation techniques suffer from operation complexity, time consumption, large sample volumes and low purity, posing significant challenges for exosomal downstream analysis. Efficient, simple, and affordable methods to isolate exosomes are crucial to carrying out relevant researches. In the last decade, emerging technologies, especially microfluidic chips, have proposed superior strategies for exosome isolation and exhibited fascinating performances. While many excellent reviews have overviewed various methods, a compressive review including updated/improved methods for exosomal isolation is indispensable. Herein, we first overview exosomal properties, biogenesis, contents, and functions. Then, we briefly outline the conventional technologies and discuss the challenges of clinical applications of these technologies. Finally, we review emerging exosomal isolation strategies and large-scale GMP production of engineered exosomes to open up future perspectives of next-generation Exo-devices for cancer diagnosis and treatment.

https://www.frontiersin.org/articles/10.3389/fbioe.2021.811971/pdf

Review on Strategies and Technologies for Exosome Isolation and Purification

Clinical and laboratory studies over recent decades have established branched evolution as a feature of cancer. However, while grounded in somatic selection, several lines of evidence suggest a Darwinian model alone is insufficient to fully explain cancer evolution. First, the role of macroevolutionary events in tumour initiation and progression contradicts Darwin's central thesis of gradualism. Whole-genome doubling, chromosomal chromoplexy and chromothripsis represent examples of single catastrophic events which can drive tumour evolution. Second, neutral evolution can play a role in some tumours, indicating that selection is not always driving evolution. Third, increasing appreciation of the role of the ageing soma has led to recent generalised theories of age-dependent carcinogenesis. Here, we review these concepts and others, which collectively argue for a model of cancer evolution which extends beyond Darwin. We also highlight clinical opportunities which can be grasped through targeting cancer vulnerabilities arising from non-Darwinian patterns of evolution.

Cancer evolution: Darwin and beyond

Modern medicine has been waging a war on cancer for nearly a century with no tangible end in sight. Cancer treatments have significantly progressed, but the need to increase specificity and decrease systemic toxicities remains. Early diagnosis holds a key to improving prognostic outlook and patient quality of life, and diagnostic tools are on the cusp of a technological revolution. Nanotechnology has steadily expanded into the reaches of cancer chemotherapy, radiotherapy, diagnostics, and imaging, demonstrating the capacity to augment each and advance patient care. Nanomaterials provide an abundance of versatility, functionality, and applications to engineer specifically targeted cancer medicine, accurate early-detection devices, robust imaging modalities, and enhanced radiotherapy adjuvants. This review provides insights into the current clinical and pre-clinical nanotechnological applications for cancer drug therapy, diagnostics, imaging, and radiation therapy.

Cancer nanotechnology: current status and perspectives.

Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care. Patients whose disease is diagnosed in its early stages have better outcomes. In this study, the authors develop a non invasive blood test based on circulating tumor DNA methylation that can potentially detect cancer occurrence even in asymptomatic patients.

/pdf/non-invasive-early-detection-of-cancer-four-years-before-1alc02y5ya.pdf

Zhen Xie

Papers

Non-invasive early detection of cancer four years before conventional diagnosis using a blood test.