Clinical Cancer Advances 2020: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.

Shortly before I was elected President of ASCO, I attended the 65th birthday party of a current patient. She had been diagnosed 10 years earlier with metastatic breast cancer and hadn't been sure she wanted to move forward with further treatment. With encouragement, she elected to participate in a clinical trial of an investigational drug that is now widely used to treat breast cancer.

Tissue and exosomal miRNA editing in Non-Small Cell Lung Cancer.

RNA editing in microRNAs has been recently proposed as a novel biomarker in cancer. Here, we investigated RNA editing by leveraging small-RNA sequencing data from 87 NSCLC (Non-Small Cell Lung Cancer) samples paired with normal lung tissues from The Cancer Genome Atlas (TCGA) combined with 26 plasma-derived exosome samples from an independent cohort. Using both the editing levels and microRNA editing expression, we detected deregulated microRNA editing events between NSCLC tumor and normal tissues.

Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer.

Purpose: Sonic hedgehog (SHH), an activating ligand of smoothened (SMO), is overexpressed in > 70% of pancreatic cancers (PCs). We investigated the impact of vismodegib, an SHH antagonist, plus gemcitabine (GV) or gemcitabine plus placebo (GP) in a multicenter phase Ib/randomized phase II trial and preclinical PC models.

Patients And Methods: Patients with PC not amenable to curative therapy who had received no prior therapy for metastatic disease and had Karnofsky performance score ≥ 80 were enrolled.

Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts.

Anaplastic large-cell lymphoma (ALCL) is a clinical and biological heterogeneous disease that includes systemic anaplastic lymphoma kinase (ALK)-positive and ALK-negative entities. To discover biomarkers and/or genes involved in ALK-negative ALCL pathogenesis, we applied the cancer outlier profile analysis algorithm to a gene expression profiling data set including 249 cases of T-cell non-Hodgkin lymphoma and normal T cells. Ectopic coexpression of ERBB4 and COL29A1 genes was detected in 24% of ALK-negative ALCL patients.

Adenosine A2A receptor plays an important role in radiation-induced dermal injury.

Ionizing radiation is a common therapeutic modality and following irradiation dermal changes, including fibrosis and atrophy, may lead to permanent changes. We have previously demonstrated that occupancy of A2A receptor (A2AR) stimulates collagen production, so we determined whether blockade or deletion of A2AR could prevent radiation-induced fibrosis. After targeted irradiation (40 Gy) of the skin of wild-type (WT) or A2AR knockout (A2ARKO) mice, the A2AR antagonist ZM241385 was applied daily for 28 d.

Personalization of cancer treatment using predictive simulation.

Background: The personalization of cancer treatments implies the reconsideration of a one-size-fits-all paradigm. This move has spawned increased use of next generation sequencing to understand mutations and copy number aberrations in cancer cells. Initial personalization successes have been primarily driven by drugs targeting one patient-specific oncogene (e.

Disulfiram suppresses growth of the malignant pleural mesothelioma cells in part by inducing apoptosis.

Dithiocarbamate compound Disulfiram (DSF) that binds with copper and functions as an inhibitor of aldehyde dehydrogenase is a Food and Drug Administration approved agent for treatment of alcoholism. Copper complexed DSF (DSF-Cu) also possesses anti-tumor and chemosensitizing properties; however, its molecular mechanisms of action remain unclear. Here we investigated malignant pleural mesothelioma (MPM) suppressive effects of DSF-Cu and the molecular mechanisms involved.

CARP-1 functional mimetics are a novel class of small molecule inhibitors of malignant pleural mesothelioma cells.

Malignant pleural mesothelioma (MPM) is an asbestos-related thoracic malignancy that is characterized by late metastases, and resistance to therapeutic modalities. The toxic side-effects of MPM therapies often limit their clinical effectiveness, thus necessitating development of new agents to effectively treat and manage this disease in clinic. CARP-1 functional mimetics (CFMs) are a novel class of compounds that inhibit growth of diverse cancer cell types.

Customized targeted therapy in Hodgkin lymphoma: hype or hope?

Although most patients with Hodgkin lymphoma (HL) are cured with primary therapy, patients with primary refractory disease or relapse after initial treatment have poor outcomes and represent an unmet medical need. Recent advances in unraveling the biology of HL have yielded a plethora of novel targeted therapies. This review provides an overview of the data behind the hype generated by these advances and addresses the question of whether or not clinically these targeted therapies offer hope for patients with HL.

Postoperative intraperitoneal 5-fluoro-2'-deoxyuridine added to chemoradiation in patients curatively resected (R0) for locally advanced gastric and gastroesophageal junction adenocarcinoma.

Purpose: Chemoradiation after surgery for locally advanced gastric cancer improves overall and relapse-free survival compared with observation. However, locoregional recurrences remain high. Accordingly, we instituted this pilot/feasibility study, including intraperitoneal 5-fluoro-2'-deoxyuridine (IP FUDR) as part of the treatment.

Chemotherapy resistance as a predictor of progression-free survival in ovarian cancer patients treated with neoadjuvant chemotherapy and surgical cytoreduction followed by intraperitoneal chemotherapy: a Southwest Oncology Group Study.

Purpose: In vitro testing of the activity of chemotherapeutic agents has been suggested as 1 method to optimally select drugs for patients with ovarian cancer. There are limited prospectively obtained data examining the clinical utility of this approach. We sought to obtain a preliminary assessment of this strategy in a trial that examined the administration of neoadjuvant chemotherapy followed by surgical cytoreduction and intraperitoneal chemotherapy in women with advanced ovarian cancer.

Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009.

Objective: Intraperitoneal (IP) chemotherapy prolongs survival in optimally reduced ovarian cancer patients. For patients in whom optimal debulking cannot be achieved, one could incorporate IP therapy post-operatively if the cancer was optimally debulked following neoadjuvant chemotherapy. We sought to evaluate overall survival (OS), progression-free survival (PFS), percent of patients optimally debulked and toxicity in patients treated with this strategy.

TCR beta chain that forms peptide-independent alloreactive TCR transfers reduced reactivity with irrelevant peptide/MHC complex.

A major feature of the TCR repertoire is strong alloreactivity. Peptides presented by allogeneic MHC are irrelevant for recognition by a subset of alloreactive T cells. To characterize peptide-independent TCRs at the molecular level, we forced the expression of a TCRbeta chain isolated from a peptide-independent alloreactive CD8+ T cell line.

Delineation of signals required for thymocyte positive selection.

Peptide/MHC complexes capable of inducing positive selection in mouse fetal thymic organ cultures fail to do so in suspension culture. Furthermore, this type of culture does not promote initial stages of differentiation, such as coreceptor down-modulation, unless peptides used for stimulation have (at least) weak agonist activity. We show in this study that signals provided in suspension culture by nonagonist peptide/MHC complexes on the surface of macrophages, even though apparently silent, are sufficient to promote complete phenotypic differentiation when CD4+CD8+ thymocytes are subsequently placed in a proper anatomical setting.

Distinct footprints of TCR engagement with highly homologous ligands.

T cell receptor engagement promotes proliferation, differentiation, survival, or death of T lymphocytes. The affinity/avidity of the TCR ligand and the maturational stage of the T cell are thought to be principal determinants of the outcome of TCR engagement. We demonstrate in this study that the same mouse TCR preferentially uses distinct residues of homologous peptides presented by the MHC molecules to promote specific cellular responses.