Perspectives in 2022

In this Perspective, Wahida et al. consider six riddles in precision oncology that must be solved to achieve better clinical responses to molecular targeted therapies.

The gut microbiota has been shown to regulate responses to various cancer therapies, and the microbial species involved and their underlying mechanisms have begun to be unravelled. In this Perspective, Fernandes and colleagues present this evidence and then outline how it could be used to develop microbiota-based therapies for patients with cancer.

This Perspective outlines the preclinical emergence of smart cell therapeutics, which when paired with machine learning analysis of genomic data could be implemented in the clinic to both enhance tumour recognition and prevent tumour escape.

Malignant cells show uninhibited proliferation and cellular plasticity, features also reminiscent of embryogenesis. In this Perspective, Sharma and colleagues present their oncofetal ecosystem concept, discuss evidence of oncofetal reprogramming in malignant and non-malignant cells, and debate the therapeutic relevance of these findings.

Structural variations (SVs), which comprise genome-level aneuploidies and rearrangements, result in both copy number changes and novel interactions between formerly distant genomic elements. This Perspective discusses how the folding of the 3D genome, and differences in its folding across cell types, affect the formation of SVs and their impact on cancer cell fitness in different cancer types.

This Perspective discusses the role of multicellular tumour networks, formed by tumour microtubes and tunnelling nanotubes, in brain tumours. It also discusses their relevance to therapy resistance and how these networks might be therapeutically targeted, and their potential relevance in other cancer types.

This Perspective discusses how polyamines, polyamine metabolism, the microbiota and the diet interconnect to establish a tumour microenvironment that facilitates the initiation and progression of cancer. It also details ways in which polyamine metabolism and function can be targeted for therapeutic benefit, including specifically enhancing the antitumour immune response.

Liquid–liquid phase separation (LLPS) has been revealed as a widespread mechanism underlying the spatiotemporal coordination of biological activities in cells. This Perspective discusses how LLPS shapes the biochemical landscape of cancer cells, providing insight into emerging findings of dysregulated LLPS promoting cancer pathology.

Cancer cell-intrinsic PDL1 signals present novel drug discovery targets and also have potential as treatment response biomarkers. This Perspective discusses our understanding of cancer cell-intrinsic PDL1 signals, mechanisms for signal controls and immunopathological consequences including resistance to cytotoxic agents, targeted small molecules and immunotherapies.

This Perspective outlines how the signalling pathways enabling metastasis are often shared with those supporting resistance to cancer therapies. Identifying nodes within these shared signalling networks that could be targeted might result in more effective therapies for the treatment of rapidly growing solid tumours.