Editors' Selections from Relevant Scientific Publications

Using phylogenetic of microdissected samples of cancer and non-cancer proliferative lesions, Nishimura et al. explored the genetic evolution of breast cancer, revealing a unique evolutionary pattern harboring der(1;16), a common driver alteration in 20% of all breast cancers and one-third of Luminal A breast cancers. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient's early 30s, leading to both cancerous and non-cancerous clones. These clones expanded significantly within the premenopausal breast before cancer diagnosis. Interestingly, multiple cancer clones originated from noncancer ancestors and there was no correlation between histology and the number of driver events, suggesting the involvement of epigenetic or microenvironmental factors in cancer development. These findings contribute to a better understanding of breast carcinogenesis and may improve early detection and prevention strategies.

Nishimura T, … Ogawa S. Nature. 2023 Aug;620(7974):607-614.

Necroptosis can drive metabolic liver diseases and lead to liver cancer, but the details are not well understood. Vucur et al. found that when pathways for necroptosis were activated in mice, hepatocytes would either die or proliferate, depending on whether the signaling factor NF-kB had been switched on. Keeping NF-kB on for long periods, maintained the cells in a “sublethal” state in which the cells leaked cytokines that drove cell proliferation and carcinogenesis. Switching NF-kB off, however, led to cell death and prevented inflammation and hepatocarcinogenesis. Furthermore, the combination of active NF-kB and signals of necroptosis predicted a poor prognosis. Inhibiting NF-kB and switching to lethal necroptosis could limit immune responses and prevent liver cancers.

Vucur M, … Luedde T. Immunity. 2023 Jul 11;56(7):1578-1595.e8.

A survey of the gut microbiome has revealed a bacterial species that could potentially serve as a probiotic for protecting women against colorectal cancer (CRC). After analyzing fecal samples from 270 CRC patients and 262 controls, Li et al. determined that Carnobacterium maltaromaticum was notably depleted in female CRC patients. Transplantation of this bacterial species significantly reduced tumor formation in females of two murine CRC models (Apc^min/− and azoxymethane-induced C57BL/6 mice). This protective effect was estrogen-dependent, and this hormone stimulates production of a cell-surface glycoprotein SLC3A2 in the colon that allows C. maltaromaticum to take up residence. Interestingly, this mechanism also relies on vitamin D—a molecule with putative chemoprophylactic properties against CRC—and C. maltaromaticum secretes a precursor compound that other commensal species subsequently convert to this beneficial metabolite.

Li Q, … Yu J. Cancer Cell. 2023 Aug 14;41(8):1450-1465.e8.

Biomarkers from the anal microbiome could provide a more effective screening system for anal cancer. Infection with human papillomavirus (HPV) can cause preinvasive, high-grade squamous intraepithelial lesions (HSILs) that can progress to cancer, especially in men who have sex with men (MSM) living with human immunodeficiency virus (HIV), but screening strategies for HSILs lack specificity. Serrano-Villar et al. analyzed samples from 213 HIV-positive MSM who had been screened for anal HSILs. They did not find any association between microbiome composition signatures and HSILs. However, they discovered that microbiome-encoded proteins responsible for producing succinyl-CoA and cobalamin, were associated with HSILs. Measuring these two biomarkers alone achieved an 82% specificity in identifying anal cancer, compared to the current screening strategy with only 34% specificity. The new screening strategy also correctly identified 82% of the false positive results produced by current clinical tests, suggesting that the two biomarkers could help improve anal cancer screening.

Serrano-Villar S, … Ferrer M. Nat Med. 2023 Jul;29(7):1738-1749.

A recent study by Lou et al. compared two different Epstein-Barr virus (EBV) testing methods for early detection of nasopharyngeal carcinoma (NPC). The researchers analyzed blood samples from 819 NPC cases in Taiwan and analyzed the EBV antibody score determined by enzyme linked immunosorbent assay. They then compared this antibody score to the plasma EBV DNA load determined by real time PCR followed by next-generation sequencing (EBV DNA algorithm). This study demonstrated a sensitivity of 88.4% for the EBV antibody score and 93.2% for the EBV DNA algorithm. The EBV antibody score had a specificity of 94.9% compared to 98.1% for the EBV DNA algorithm. Early-stage NPC sensitivities were similar for both methods. This study provided a critical independent validation and direct assessment of these two screening methods for NPC detection. It may help inform early testing strategies, especially for populations at risk.

Lou PJ, … GEV-NPC Group on behalf of the Collaborative Group. J Clin Oncol. 2023 Jul 21:JCO2201979.

Canada's colorectal cancer (CRC) screening guidelines target people aged 50 to 74, but rising incidence of early-onset CRC suggests potential benefit in targeting younger individuals. Kalyta et al. employed a digital tool called OncoSim-CRC, which uses real-world data to simulate the impact of changes in clinical practice, to evaluate the costs and benefits of initiating biennial fecal immunochemical testing earlier. The predicted public health gains were notable, with 12,188 fewer CRC cases and 5,261 fewer deaths if screening is initiated at age 45—and a roughly 50% further reduction in both metrics when starting at age 40, with a commensurate increase in quality-adjusted life-years saved. This simulation also indicated that starting earlier would be cost-effective, although a broader assessment of impact on the Canadian healthcare system is needed.

Kalyta A, … Loree JM. JAMA Oncol. 2023 Jul 20:e232312.