In this Comment, the authors outline the emerging rationale for the clinical use of tumour budding, a histological manifestation of tumour cell invasion, as a diagnostic tool and biomarker in colorectal cancer.
Clinical studies can teach us a great deal about the processes and mechanisms underlying cancer, and they also remind us of aspects of cancer that we still do not understand. For example, why patients with metastatic special neuroblastoma undergo spontaneous tumour regression; why some rare types of cancer are metaplastic; and why some patients are exceptional responders to chemotherapy. In recognition of these types of informative findings from the clinic that are often overlooked by laboratory-based cancer researchers, we have commissioned a series of Clinical insights Comment articles. Thinking more broadly about these more unusual aspects of cancer might help us overcome some of the current stumbling blocks in cancer research.
Most of our current knowledge of melanoma is derived from the study of patients from populations of European descent, for whom public health, sun protection initiatives and screening measures have appreciably decreased disease mortality. Notably, some melanoma subtypes that most commonly develop in other populations are not associated with exposure to ultraviolet (UV) light, suggesting a different disease aetiology. Further study of these subtypes is necessary to understand their risk factors and genomic architecture, and to tailor therapies and public health campaigns to benefit patients of all ethnic groups.
Hosteet al. discuss whether allergic immune responses, which have been observed to be protective against some types of cancer, can be activated to target cancer, and what the mechanism of antitumour allergic responses might be.
Why do inherited germline mutations in common cancer-associated genes cause a restricted pattern of tissue-specific malignancies, but when somatic mutations occur in these genes they exhibit far less tissue restriction?
This Comment article argues that we should more comprehensively study the biology of benign tumours, as this might provide crucial insights into our understanding of cancer biology and metastasis.
Ottini discusses what we understand about male breast cancer and what we can learn from it in terms of breast cancer pathogenesis.
The incidence of cancer in the small intestine is considerably lower than the incidence of cancer in the large intestine. Why might this be? This article suggests that the microbiota might be part of the explanation for this difference.
Chesler discusses immune-mediated paraneoplasias as evidence of the fundamental relationship between cancer and the immune system.
Do we all develop a covert cancer as we age?
NUT midline carcinoma, a squamous cell carcinoma, is one of the most aggressive human cancers, and there is a desperate need for effective therapies for patients with this disease.
Metaplastic breast carcinoma (MBC) accounts for 0.2–5% of invasive breast cancers. The majority of MBCs have a triple-negative phenotype, are highly heterogeneous and respond poorly to chemotherapy. Understanding their divergent differentiation and identifying the cell of origin might provide some much-needed insight into this disease.
Stage MS neuroblastoma is unique in that it regresses without treatment. Could a better understanding of the biology of these tumours inform how high-risk neuroblastoma and other paediatric malignancies are treated?
Cancer of unknown primary site is both a challenging clinical problem and a disease that provides potential insight into the mechanisms that underlie early metastasis.