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Shaw and colleagues discuss the oncogenic roles of ALK in lung cancer, targeting approaches and the mechanisms underlying acquired resistance to ALK-directed therapy.
High-fat diet and the secretome of breast tumors prime distant organs for metastasis formation. During lung priming, alveolar type II cells increase the release of palmitate, which is oxidized to acetyl-CoA by metastasizing breast cancer cells, where the increased acetylation of the NF-κB subunit p65 activates a pro-metastatic transcriptional program.
Using an unbiased algorithm based on kinase–phosphorylation site interactions that is applicable to any proteomic dataset, we identified and experimentally validated two protein kinases (PKCδ and DNA-PKcs) as the master kinases that drive two functional subtypes of glioblastoma multiforme and are potential therapeutic targets of other cancer subtypes.
Somatic mutations in cancer genomes are caused by multiple mutational processes, each generating characteristic mutational signatures. Our systematic mutational signature analysis of single base substitutions and small insertions and deletions in pediatric cancers indicates that the contribution of signatures of homologous recombination repair defect is limited and identifies a leukemia-specific signature.
Patients with blood cancer have fewer antibodies after SARS-CoV-2 vaccination — but recent work shows that these antibodies seem to bind to viral spike protein more strongly than those in matched controls. In addition, another study finds that convalescent or vaccinee plasma might improve COVID-19 outcomes in those with blood cancer.
Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and treatment options. A new study reveals a unique inflammatory signature in pediatric and adult AML malignant cells that is associated with the infiltration of atypical B cells in the bone marrow microenvironment, which adds an independent layer of prognostic information.
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of mortality worldwide. Integrative analysis of the genome, transcriptome and proteome of PDAC tissues, also known as proteogenomic analysis, provides insight into the biology of this cancer and is a resource for therapeutic discovery.
Modulation of T cell immune checkpoints combined with inhibition of chemokine receptors on myeloid-derived suppressor cells can reprogram the highly suppressive tumor immune microenvironment of pancreatic ductal adenocarcinoma (PDAC), and generates durable complete responses in a PDAC mouse model. These results provide a testable clinical regimen for human PDAC.
Developing approaches to identify patients who may benefit from specific treatments is an important area of research. A study now defines an HDAC6 score to predict the response of patients with breast cancer to the HDAC6 inhibitor ricolinostat and characterizes its anti-tumor effects with preclinical mechanistic work and a phase 1b clinical trial.
Overall survival for children with rare, relapsed, metastatic and/or refractory cancers has remained unacceptably low over the past four decades. A new precision oncology study introduces an integrative germline and somatic sequencing approach that could breach this impasse to advance cures for children with cancer.
Piccolo and colleagues discuss the current knowledge on YAP/TAZ biology in cancer, highlighting recent progress in the field and discussing open questions, as well as potential clinical implications.
Glioblastoma (GBM) brain tumor cells exhibit pronounced phenotypic plasticity, but exactly how this enables GBMs to inevitably resist standard treatment is not known. A new study uses multilevel molecular profiling of pre- and post-treatment human GBMs to shed light on treatment response with single-cell and spatial resolution.
Twelve early career investigators share experiences from the process of starting their laboratories throughout the past year, and reflect on the challenges faced and the opportunities seized.
Pancreatic ductal cells transport bicarbonate from blood to pancreatic juice. A study shows that pancreatic cancer retains SLC4A4-mediated bicarbonate import to fuel cancer growth via enhanced glycolysis and establish a pro-tumorigenic immune microenvironment. Targeting SLC4A4 mitigates acidosis and can be combined with checkpoint blockade.
Persistent senescent cancer cells have tumor-promoting potential, making their selective elimination a prime therapeutic objective. The death receptor inhibitor cFLIP has now been shown to counter the susceptibility of senescent cells to DR5-mediated extrinsic apoptosis, which can be therapeutically exploited.
Combinations of immune-checkpoint blockade and radiotherapy to modulate antitumor immunity have mainly focused on manipulating T cells. A study now shows that combining radiotherapy with activation of macrophages yields potent, abscopal effects in mouse tumor models that may be ready for translation into early clinical trials.
Pancreatic ductal carcinoma exists within a heterogenous and complex microenvironment that imposes austere conditions with limited nutrient availability. Clonally separable neoplastic cell populations are now shown to segregate into two distinct metabolic configurations, facilitating symbiotic intratumoral crosstalk to support survival and growth.
