Reviews & Analysis

Liquid biopsy approaches hold great promise in early cancer diagnosis or minimal residual disease monitoring for cancer recurrence. Herein, the authors evaluate contemporary next-generation sequencing approaches to circulating tumour DNA detection in these contexts, with a focus on studies in patients with non-small-cell lung cancer. They discuss the feasibility of introducing these strategies into the clinic, highlighting the technical and analytical challenges, as well as possible solutions.

CARMENA, a trial comparing the efficacy of sunitinib alone to that of nephrectomy followed by sunitinib in patients with primary metastatic renal cell carcinoma who require targeted therapy has demonstrated the non-inferiority of systemic therapy alone. The data provided by this and other studies argue for a lesser role of surgery in the management of these patients.

Following the success of poly(ADP-ribose) PARP inhibitors in patients with BRCA1/2 mutations, considerable research interest has emerged in the discovery of alternative forms of synthetic lethality. In this Review, the authors summarize the potential of various novel forms of synthetic lethality to further improve the treatment of patients with cancer.

The combination of radiotherapy and immune-checkpoint inhibition (ICI) has generated considerable excitement among oncologists, and numerous clinical trials are currently exploring the efficacy of this approach; however, the safety and tolerability of this combination remains incompletely understood. In this Review, the authors describe the available data on safety considerations in patients receiving radiotherapy in combination with ICI.

Developments in the treatment of advanced-stage hepatocellular carcinoma include novel locoregional interventions aiming to induce tumour necrosis and systemic treatments targeting the biological mechanisms of tumour progression, thus aiming to delay progression. These approaches fiercely battle to provide the best survival, but their lack of success to date suggests that they might be better tested as a complementary approach.

PapSEEK, a novel liquid-based cytology test, enabled the highly specific detection of endometrial and ovarian cancer in a retrospective study. Herein, I discuss potential applications of this tool, both for cancer screening of asymptomatic populations and for the early diagnosis of cancer in symptomatic women.

New treatment options for patients with resected stage III melanoma have been established with the publication of the results of four pivotal randomized clinical trials, resulting in three drug approvals, with a forth expected, all within only 4 years. Herein, we put these advances into context.

The prognostic significance of residual disease, measured by flow cytometry or PCR-based assays, has been established in patients with acute myeloid leukaemia (AML). The results of a recent study involving almost 500 patients in morphological remission demonstrate that detection of persistent mutations using next-generation sequencing provides information complementary to that obtained using the established methods and offer insights into AML evolution.

Emerging evidence indicates that tumour-derived extracellular vesicles (EVs), notably exosomes, mediate intercellular communication to promote cancer development and progression. Herein, the authors discuss EV properties and physiological functions, particularly their pro-metastatic effects, and highlight the diagnostic and therapeutic potential of EVs in cancer.

Recent genomic and transcriptomic analyses of diffuse large B cell lymphoma (DLBCL) have provided important new insights into the heterogeneous biology of this disease. The findings provide opportunities to improve treatment strategies, although considerable work is needed to establish and optimize the clinical applicability and utility of molecular classifications of DLBCL.

Evidence of the functional roles of non-coding RNAs in cancer is expanding, and the potential of these RNAs as diagnostic and prognostic biomarkers is increasingly recognized. Herein, the authors review the recent developments in these areas and provide compendiums of circulating microRNAs and long non-coding RNAs that have promise as diagnostic and prognostic cancer biomarkers.

In recent years, a number of novel agents have been added to the therapeutic armamentarium for patients with chronic lymphocytic leukaemia (CLL). Herein, Jan A. Burger and Susan O’Brien outline the emerging paradigm of individualized therapy for patients with CLL aimed at exploiting the advantages of these novel agents but also integrating traditional therapies for selected patients.

The affordability of newly approved anticancer agents is a challenge to many national health services and reimbursement systems. Therefore, we have developed an approach based upon the adoption of a novel model of price setting and herein provide examples of how it might be implemented. This model is intended to alter the balance between social and economic entrepreneurship.

Patients with advanced-stage urothelial carcinoma typically receive chemotherapy and might also receive immune-checkpoint inhibitors following disease progression. However, the majority of patients will ultimately develop resistance to treatment. In this Review, the authors describe the evolutionary mechanisms of treatment resistance in patients with urothelial carcinoma.

Helicobacter pylori eradication therapy is effective in preventing gastric cancer, even in patients with advanced pre-neoplastic lesions (gastric atrophy and/or intestinal metaplasia). We must now focus on how to accomplish the goal of eliminating gastric cancer-related death worldwide; strategies for screening and treatment of gastric neoplasia (primary prevention) and post-treatment surveillance (secondary prevention) are discussed herein.

After almost 20 years of negative trials of novel therapies for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), two androgen receptor antagonists have shown favourable outcomes in phase III trials involving patients with high-risk nmCRPC. Herein, the history of nmCRPC and clinical trials in this disease setting are discussed and a perspective on molecular imaging and clinical management of nmCRPC is offered.

The multiple myelomas (MMs) are heterogeneous malignancies that are nearly always associated with chromosomal abnormalities, which can be considered either primary or secondary abnormalities. The classification of MM according to the underlying primary cytogenetic abnormality might enable the development of better treatment strategies. The authors describe treatment approaches that consider the current standard of care for patients with MM along with recommendations for certain subgroups of patients.

Patients with sarcomas have historically been treated with surgery and/or chemotherapy, although the outcomes achieved with these approaches, especially in advanced-stage disease, are often disappointing. In this Review, the authors describe the opportunities created by selective use of targeted therapies on the basis of the biological characteristics of individual tumours.

Despite extensive research efforts, very few DNA methylation-based biomarkers have been implemented clinically. In this Perspective, the authors describe the importance of considering the genomic locations examined in determining the diagnostic or prognostic relevance of putative DNA methylation-based biomarkers.

The tumour stroma is a component of the tumour microenvironment and has crucial roles in tumour initiation, progression, and metastasis. Most anticancer therapies target cancer cells specifically, but the tumour stroma can promote resistance to such therapies. Herein, the authors provide an overview of the complex cancer cell–tumour stroma interactions and discuss how novel treatment strategies should combine anticancer and antistromal agents.