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Cancer Prevention Month

Cancer is a major public health challenge and a leading cause of death worldwide. In 2018, about 1 in 6 deaths was due to cancer. On 4 February we celebrate World Cancer Day 2020, a global initiative to raise awareness and to encourage cancer prevention, detection, and treatment.

In the US, February is also National Cancer Prevention Month. Over the last few years, research has demonstrated that some cancers can be prevented by reducing exposure to cancer risk factors and implementing prevention strategies. Simple steps, including healthy lifestyle changes (cessation of smoking, regular exercise, body weight controlling and reduced sun exposure) and vaccinations against viruses that cause certain cancers can indeed reduce risk. Cancer burden can also be reduced through early detection and management of patients who develop cancer, as it has been demonstrated that many cancers have a better chance of cure if diagnosed early and treated adequately.

It is therefore imperative to increase dissemination of our current knowledge of cancer causes, treatment and prevention. With this aim, this month we would like to highlight the latest research articles published in Nature Communications covering all aspects from ‘omics studies and disease mechanisms to diagnostic and therapeutic approaches.

Featured articles

Autophagy declines with age, yet it is unclear if restoration of autophagy extends lifespan. Here, the authors demonstrate in murine models that the inhibition of Atg5 induces ageing phenotypes and reduces lifespan, whilst autophagy restoration partially reverses these phenotypes with accelerated tumorigenesis.

Article | Open Access | | Nature Communications

Immune-mediated selection pressures impact the clonal evolution of tumours. Here, in hepatocellular carcinoma the authors map spatio-temporal interactions between tumor and immune cells, highlighting the regulatory substrate of intra-tumoural heterogeneity that correlates with regional adaptive immune responses.

Article | Open Access | | Nature Communications

Cancer therapy using oncolytic virus has shown pre-clinical and clinical efficacy. Here, the authors report ExtraCRAd, an oncolytic virus cloaked with tumour cell membrane and report its therapeutic effects in vitro and in vivo in multiple mouse tumour models.

Article | Open Access | | Nature Communications

It is known that estrogens can affect the immune response to cancer. Here, the authors show that estrogen depletion through ovariectomy reduces the extent of liver metastasis and that this is accompanied by a decrease in the number and function of immunosuppressive cells in the metastatic microenvironment.

Article | Open Access | | Nature Communications

UVRAG is involved in autophagy, which loses its tumour suppressor functions when in its truncated form in cancers. Here, the authors use a mouse model that inducibly express this truncated protein and show impaired autophagy, enhanced inflammation and β-catenin stabilisation, which promotes spontaneous tumorigenesis.

Article | Open Access | | Nature Communications

It is unclear whether fallopian tube epithelium or ovarian surface epithelium is the cell-of-origin of high grade serous ovarian carcinoma (HGSOC). Here the authors report a dualistic origin for HGSOC using genetically engineered mouse models and observe differential chemotherapy sensitivity depending on the cell-of-origin.

Article | Open Access | | Nature Communications

MAPK-targeted therapies fail to achieve complete remission. Here, the authors show that anti-apoptosis resistance is acquired in these targeted therapies through the mRNA destabilization of NOXA which leads to dependence on MCL-1, and that sequential combination of MCL-1 inhibition with targeted therapies overcomes this resistance.

Article | Open Access | | Nature Communications

DNA-dependent protein kinase (DNA-PK) plays a major role in the DNA damage response upon double-strand break formation. Here, the authors show that the DNA-PK inhibitor AZD7648, enhances the activity of radiotherapy, chemotherapy and the PARP inhibitor olaparib in multiple mouse tumour models.

Article | Open Access | | Nature Communications

In breast cancer, dormant cancer cells may develop into bone metastases. Here, the authors demonstrate that microenvironmental IL1β stimulates metastatic breast cancer cell colonisation in the bone via IL1β-NFKB/CREB-Wnt pathway activation and cancer stem cell colony formation

Article | Open Access | | Nature Communications

The mechanism of force production by invadopodia is unclear. Here, the authors show that cell surface MT1-MMP when in contact with collagen, induces Arp2/3 branched actin polymerisation on the concave side of invadopodia, which generates a pushing force along with collagen cleavage by MT1-MMP to invade.

Article | Open Access | | Nature Communications

Interval cancer patients are more likely to carry rare gene mutations than screen-detected breast cancer patients. Here, the authors report that interval cancer patients are more likely cancer survivors and are at a greater risk of developing other non-breast tumors.

Article | Open Access | | Nature Communications

In multiple myeloma, a 4;14 translocation induces overexpression of histone methyltransferase NSD2, resulting in expansion of H3K36me2 and shrinkage of H3K27me3 domains. Here the authors find that CTCF, H3K27ac and gene expression changes cluster within a subset of insulated domains implicating 3D chromosome organization as a key factor in the NSD2-mediated phenotype.

Article | Open Access | | Nature Communications

In the treatment of pancreatic ductal adenocarcinoma (PDAC), comorbidities such as cachexia limit quality of life and survival. Here, the authors show TLR7/8 agonist R848 remodels host and tumour immune responses, promoting survival and attenuating cachexia in murine models of PDAC.

Article | Open Access | | Nature Communications

Cancer associated fibroblasts (CAFs) are known to promote pro-tumorigenic inflammation. Here, the authors show that CAFs sense tissue damage and activate NLRP3 inflammasome and pro-inflammatory IL-1β secretion, and CAF-derived inflammasome signalling promotes breast tumour growth and metastasis.

Article | Open Access | | Nature Communications

In prostate cancer, chromatin structure can impact the transcriptome. Here, the authors develop high resolution chromatin interaction maps in prostate cancer cells using in situ Hi-C, revealing prostate cancer-specific TADs and enhancer-promoter loops surrounding the androgen receptor (AR) locus.

Article | Open Access | | Nature Communications

Interactions between germline variants and somatic mutations is a relatively unexplored topic in cancer. Here, in Ewing sarcoma, the authors show that binding of the oncogenic EWSR1-FLI1 fusion transcription factor to a polymorphic enhancer-like DNA element controls MYBL2, whose high expression correlates with prognosis.

Article | Open Access | | Nature Communications

The previous efforts to reprogramme tumour-associated macrophages (TAMs) to M1 phenotype have caused undesired side-effects. Here, the authors report targeted nanocarriers for delivering mRNA encoding M1-polarizing transcription factors to TAMs and show their efficacy in multiple mouse tumour models.

Article | Open Access | | Nature Communications

More featured articles

Cancer stem cells (CSCs) comprise a putative population that can drive growth and resistance. Here, in glioblastoma models the authors show that rather than being a distinct clonal entity, the CSC population represents a plastic state adoptable by most cancer cells via reversible state transitions induced by the microenvironment.

Article | Open Access | | Nature Communications

In chronic lymphocytic leukemia (CLL), evolution is driven by transcriptional and epigenetic heterogeneity. Here, the authors integrate epigenomic analyses to show how intra-tumoral epigenetic diversity results in divergent chromatin states in CLL cells, increasing cell-to-cell transcriptional heterogeneity.

Article | Open Access | | Nature Communications

Currently available Raman scanners are limited in speed to acquire images of clinically relevant sizes in cancer imaging. Here, the authors developed a DNA based design principle for Raman-Fluorescence bimodal nanoparticles and demonstrate real-time, high precision image-guided tumor resections and photothermal ablation of cancer.

Article | Open Access | | Nature Communications

Bronchial premalignant lesions can potentially progress to lung squamous cell carcinoma. Here, the authors profile bronchial biopsies from high-risk smokers by RNA sequencing and identify four molecular subtypes of premalignant lesions and an immune molecular signature that associates with lesion progression.

Article | Open Access | | Nature Communications

Immunotherapy for the treatment of cancer can be complicated by side effects and poor efficacy. Here, the authors use a nanoparticle-based approach in combination with a TLR7 agonist and sonodynamic therapy, and find that when used together with anti-PD-L1, tumour formation and metastases are impacted.

Article | Open Access | | Nature Communications

Colorectal cancer cells can acquire resistance to MEK inhibition due to BRAF or KRAS amplification. Here, the authors show that while MEK inhibitor withdrawal in BRAF mutant cells restores sensitivity to the inhibitor through the loss of BRAF amplification mediated by a p57-dependent mechanism, drug withdrawal from KRAS mutant cells does not restore sensitivity but results in EMT and chemoresistance.

Article | Open Access | | Nature Communications

PARP inhibitors are mainly used to treat BRCA1/2 mutated cancers. Here, the authors show that MYC amplified glioblastomas are sensitive to PARP inhibition due to CDK18 repression, which impairs ATR regulated homologous recombination repair, and that ATR inhibition sensitises glioblastomas to PARP inhibition.

Article | Open Access | | Nature Communications

The BCL-2 mutation G101V reduces venetoclax affinity and confers drug resistance in patients with chronic lymphocytic leukaemia. Here, the authors present crystal structures and biochemical analyses of venetoclax bound to BCL-2 and the G101V mutant, revealing the structural basis for venetoclax resistance.

Article | Open Access | | Nature Communications

CD19 CAR-T cells have achieved some success in treating myeloma patients despite the limited detection of the CD19 antigen. Here, the authors show using dSTORM that 10/14 myeloma samples studied express ultra-low levels of CD19, which are sufficient for engaging CAR-T cells in vitro.

Article | Open Access | | Nature Communications

MRI scans of glioblastoma patients can be misleading and some patients appear to show features of progressive disease although they respond to treatment. Here, the authors use MRI images of progressive disease or pseudoprogression and build a classifier using machine learning to distinguish the two.

Article | Open Access | | Nature Communications

PIK3CA mutations and ARID1A loss co-exist in endometrial neoplasms. Here, the authors show that these co-mutations drive gene expression profiles correlated with differential chromatin accessibility and ARID1A binding in the endometrial epithelium, resulting in partial EMT and myometrial invasion.

Article | Open Access | | Nature Communications

Plasma proteins may severely affect the in vivo performance of liposomes. Here, the authors develop bio-inspired liposomes that specifically absorb brain-targeted apolipoproteins and preserve their bioactivities, thereby achieving efficient brain targeting with minor influence on immunocompatibility of liposomes.

Article | Open Access | | Nature Communications

The definition of regulatory landscape at chronic lymphocytic leukaemia (CLL) risk loci is limited. Here, the authors perform an epigenomic characterisation of 42 known risk loci in CLL and normal B cells at different developmental stages and show active chromatin and target genes in the risk loci.

Article | Open Access | | Nature Communications

Subtypes of cancer associated fibroblasts can both promote and suppress tumorigenesis. Here, the authors investigate how p53 status in pancreatic cancer cells affects their interaction with cancer associated fibroblasts, and report perlecan as a mediator of the pro-metastatic environment.

Article | Open Access | | Nature Communications

Each cell type in the tumour microenvironment has unique metabolic demands enabling specific functions. Here the authors use published single-cell RNA-seq data and develop a computational framework to better understand the heterogeneity of tumour metabolism, highlighting the discordance between results obtained from single cells and bulk tumours.

Article | Open Access | | Nature Communications

More featured articles

Cancer stem cells (CSCs) comprise a putative population that can drive growth and resistance. Here, in glioblastoma models the authors show that rather than being a distinct clonal entity, the CSC population represents a plastic state adoptable by most cancer cells via reversible state transitions induced by the microenvironment.

Article | Open Access | | Nature Communications

In chronic lymphocytic leukemia (CLL), evolution is driven by transcriptional and epigenetic heterogeneity. Here, the authors integrate epigenomic analyses to show how intra-tumoral epigenetic diversity results in divergent chromatin states in CLL cells, increasing cell-to-cell transcriptional heterogeneity.

Article | Open Access | | Nature Communications

Currently available Raman scanners are limited in speed to acquire images of clinically relevant sizes in cancer imaging. Here, the authors developed a DNA based design principle for Raman-Fluorescence bimodal nanoparticles and demonstrate real-time, high precision image-guided tumor resections and photothermal ablation of cancer.

Article | Open Access | | Nature Communications

Bronchial premalignant lesions can potentially progress to lung squamous cell carcinoma. Here, the authors profile bronchial biopsies from high-risk smokers by RNA sequencing and identify four molecular subtypes of premalignant lesions and an immune molecular signature that associates with lesion progression.

Article | Open Access | | Nature Communications

Immunotherapy for the treatment of cancer can be complicated by side effects and poor efficacy. Here, the authors use a nanoparticle-based approach in combination with a TLR7 agonist and sonodynamic therapy, and find that when used together with anti-PD-L1, tumour formation and metastases are impacted.

Article | Open Access | | Nature Communications

Colorectal cancer cells can acquire resistance to MEK inhibition due to BRAF or KRAS amplification. Here, the authors show that while MEK inhibitor withdrawal in BRAF mutant cells restores sensitivity to the inhibitor through the loss of BRAF amplification mediated by a p57-dependent mechanism, drug withdrawal from KRAS mutant cells does not restore sensitivity but results in EMT and chemoresistance.

Article | Open Access | | Nature Communications

PARP inhibitors are mainly used to treat BRCA1/2 mutated cancers. Here, the authors show that MYC amplified glioblastomas are sensitive to PARP inhibition due to CDK18 repression, which impairs ATR regulated homologous recombination repair, and that ATR inhibition sensitises glioblastomas to PARP inhibition.

Article | Open Access | | Nature Communications

The BCL-2 mutation G101V reduces venetoclax affinity and confers drug resistance in patients with chronic lymphocytic leukaemia. Here, the authors present crystal structures and biochemical analyses of venetoclax bound to BCL-2 and the G101V mutant, revealing the structural basis for venetoclax resistance.

Article | Open Access | | Nature Communications

CD19 CAR-T cells have achieved some success in treating myeloma patients despite the limited detection of the CD19 antigen. Here, the authors show using dSTORM that 10/14 myeloma samples studied express ultra-low levels of CD19, which are sufficient for engaging CAR-T cells in vitro.

Article | Open Access | | Nature Communications

MRI scans of glioblastoma patients can be misleading and some patients appear to show features of progressive disease although they respond to treatment. Here, the authors use MRI images of progressive disease or pseudoprogression and build a classifier using machine learning to distinguish the two.

Article | Open Access | | Nature Communications

PIK3CA mutations and ARID1A loss co-exist in endometrial neoplasms. Here, the authors show that these co-mutations drive gene expression profiles correlated with differential chromatin accessibility and ARID1A binding in the endometrial epithelium, resulting in partial EMT and myometrial invasion.

Article | Open Access | | Nature Communications

Plasma proteins may severely affect the in vivo performance of liposomes. Here, the authors develop bio-inspired liposomes that specifically absorb brain-targeted apolipoproteins and preserve their bioactivities, thereby achieving efficient brain targeting with minor influence on immunocompatibility of liposomes.

Article | Open Access | | Nature Communications

The definition of regulatory landscape at chronic lymphocytic leukaemia (CLL) risk loci is limited. Here, the authors perform an epigenomic characterisation of 42 known risk loci in CLL and normal B cells at different developmental stages and show active chromatin and target genes in the risk loci.

Article | Open Access | | Nature Communications

Subtypes of cancer associated fibroblasts can both promote and suppress tumorigenesis. Here, the authors investigate how p53 status in pancreatic cancer cells affects their interaction with cancer associated fibroblasts, and report perlecan as a mediator of the pro-metastatic environment.

Article | Open Access | | Nature Communications

Each cell type in the tumour microenvironment has unique metabolic demands enabling specific functions. Here the authors use published single-cell RNA-seq data and develop a computational framework to better understand the heterogeneity of tumour metabolism, highlighting the discordance between results obtained from single cells and bulk tumours.

Article | Open Access | | Nature Communications