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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.
Immunovirotherapy is a promising therapeutic strategy for glioblastoma (GBM), a deadly tumor for which effective treatments remain a clinical need. A new study describes an oncolytic herpes simplex virus (oHSV) armed with a bispecific anti-EGFR–CCL5 fusion protein that activates innate and adaptive antitumor immune responses that are highly efficacious in preclinical GBM models.
Intratumoral activation of the complement cascade may have therapeutic potential in patients with lung cancer with strong EGFR signaling, shows a new study. EGFR-triggered expression of CD55 and CD59 prevents opsonization of tumor cells, inhibits antitumor immunity and confers resistance to immune-checkpoint inhibitors.
The efficacy of talazoparib and other PARP inhibitors has been primarily reported in germline BRCA mutation carriers. New results establish germline mutations in PALB2, but not in other homologous recombination (HR) genes, as targets for PARP inhibitors in breast cancer, whereas the added predictive value of HR signatures remains uncertain.
Increasing evidence links RNA methyltransferases to DNA damage repair. METTL16 is now shown to antagonize homologous recombination by preventing DNA-end resection via MRE11. Thus, METTL16 may represent a cancer vulnerability that can be used to identify patients able to benefit from combination therapies with DNA-damaging agents.
Therapeutic resistance in prostate cancer can be driven by lineage plasticity, but the mechanisms behind this are unclear, and therapies to prevent or reverse the process are nonexistent. A new study reveals the JAK/STAT signaling axis as a driver of lineage plasticity with tremendous therapeutic potential.
The identification of tumor-reactive T cells using phenotypic markers is now well established in treatment-naive tumors. It is unclear, however, whether these markers can also be useful after immune checkpoint blockade (ICB). A new study finds that CXCL13 expression robustly identifies tumor-reactive T cells before and after ICB and is associated with treatment response.
Schmatko et al. review the application of artificial intelligence to digitized histopathology for cancer diagnosis, prognosis and classification and discuss its potential utility in the clinic and broader implications for cancer research and care.
Mesenchymal-like and pluripotency-like programs coordinate the dissemination and long-lived dormancy of early breast cancer cells. The transcription factor ZFP281 controls these programs, preventing the acquisition of an epithelial-like proliferative phenotype and serving as a previously unrecognized barrier to metastasis.
Immunotherapy has shown great promise in the treatment of patients with advanced non-small-cell lung cancer. We show that integration of data collected during diagnostic clinical work-up with machine learning has the potential to improve predictions of response to immunotherapy and to identify the patients most likely to benefit.
