Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer.

Purpose: To evaluate the efficacy and tolerability of two doses of gefitinib (Iressa [ZD1839]; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with pretreated advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: This was a randomized, double-blind, parallel-group, multicenter phase II trial. Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens (at least one containing platinum) were randomized to receive either 250-mg or 500-mg oral doses of gefitinib once daily.

Mechanism of Morphology Development in HDGEBA/PAMS Hybrid Thermosets: Monte Carlo Simulation and LSCM Study.

Reactive combinations of aliphatic epoxy resins and functional polysiloxanes form a class of hybrid thermosetting materials with properties that may come from both the organic and the inorganic phases. The two typically immiscible phases form a suspension whose morphology, composition, and thermal properties vary with curing time. The aim of this research was to elucidate the mechanism by which morphology changed with time and to simulate it through Metropolis-Monte Carlo.

Chitosan as a Tool for Sustainable Development: A Mini Review.

New developments require innovative ecofriendly materials defined by their biocompatibility, biodegradability, and versatility. For that reason, the scientific society is focused on biopolymers such as chitosan, which is the second most abundant in the world after cellulose. These new materials should show good properties in terms of sustainability, circularity, and energy consumption during industrial applications.

Concentration Effect over Thermoresponse Derived from Organometallic Compounds of Functionalized Poly(-isopropylacrylamide--dopamine Methacrylamide).

The functionalization of smart polymers is opening a new perspective in catalysis, drug carriers and biosensors, due to the fact that they can modulate the response regarding conventional devices. This smart response could be affected by the presence of organometallic complexes in terms of interactions which could affect the physical chemical properties. In this sense, the thermoresponsive behavior of copolymers based on -isopropylacrylamide (NIPAM) could be affected due to the presence of hydrophobic groups and concentration effect.

Neoadjuvant eribulin in HER2-negative early-stage breast cancer (SOLTI-1007-NeoEribulin): a multicenter, two-cohort, non-randomized phase II trial.

Eribulin prolongs overall survival in patients with pre-treated advanced breast cancer. However, no biomarker exists to prospectively select patients who will benefit the most from this drug. SOLTI-1007-NeoEribulin is a phase II, open-label, two-cohort, exploratory pharmacogenomic study in patients with clinical stage I-II HER2-negative breast cancer receiving neoadjuvant eribulin monotherapy treatment.

Patient-reported function, health-related quality of life, and symptoms in APHINITY: pertuzumab plus trastuzumab and chemotherapy in HER2-positive early breast cancer.

Background: We assessed health-related quality of life (symptoms of therapy/patient functioning/global health status), in APHINITY (pertuzumab/placebo, trastuzumab, and chemotherapy as adjuvant HER2-positive early breast cancer therapy).

Methods: Patients received 1 year/18 cycles of pertuzumab/placebo with trastuzumab and chemotherapy and completed EORTC QLQ-C30 and BR23 questionnaires until 36 months post-randomisation/disease recurrence. Changes ≥10 points from baseline were considered clinically meaningful.

Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D).

Aim: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial.

Patients And Methods: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS).

FOXA1 Mutations Reveal Distinct Chromatin Profiles and Influence Therapeutic Response in Breast Cancer.

Mutations in the pioneer transcription factor FOXA1 are a hallmark of estrogen receptor-positive (ER) breast cancers. Examining FOXA1 in ∼5,000 breast cancer patients identifies several hotspot mutations in the Wing2 region and a breast cancer-specific mutation SY242CS, located in the third β strand. Using a clinico-genomically curated cohort, together with breast cancer models, we find that FOXA1 mutations associate with a lower response to aromatase inhibitors.

Ultrasound-assisted exfoliation of a layered 2D coordination polymer with HER electrocatalytic activity.

Large blue rectangular crystals of the 2D layered coordination polymer 1 have been obtained. The interest for this complex is two-fold. First, complex 1 is made of 2D layers packing along the (0-11) direction favored by the presence of lattice and coordinated water molecules.

Inhibition of Bruton tyrosine kinase in patients with severe COVID-19.

Patients with severe COVID-19 have a hyperinflammatory immune response suggestive of macrophage activation. Bruton tyrosine kinase (BTK) regulates macrophage signaling and activation. Acalabrutinib, a selective BTK inhibitor, was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation), 18 of whom had increasing oxygen requirements at baseline.

A Phase II Trial of Cabozantinib in Hormone Receptor-Positive Breast Cancer with Bone Metastases.

Background: We assessed the antitumor activity of cabozantinib, a potent multireceptor oral tyrosine kinase inhibitor, in patients with hormone receptor-positive breast cancer with bone metastases.

Patients And Methods: In this single-arm multicenter phase II study, patients received an initial starting dose of 100 mg, later reduced to 60 mg, per day. The primary endpoint was the bone scan response rate.

Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy.

Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab.

Pan-Cancer Efficacy of Vemurafenib in -Mutant Non-Melanoma Cancers.

mutations occur in a wide range of tumor types, and RAF inhibition has become standard in several of these cancers. Despite this progress, mutations have historically been considered a clear demonstration of tumor lineage context-dependent oncogene addiction, based predominantly on the insensitivity to RAF inhibition in colorectal cancer. However, the true broader activity of RAF inhibition pan-cancer remains incompletely understood.

ARID1A determines luminal identity and therapeutic response in estrogen-receptor-positive breast cancer.

Mutations in ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, are the most common alterations of the SWI/SNF complex in estrogen-receptor-positive (ER) breast cancer. We identify that ARID1A inactivating mutations are present at a high frequency in advanced endocrine-resistant ER breast cancer. An epigenome CRISPR-CAS9 knockout (KO) screen identifies ARID1A as the top candidate whose loss determines resistance to the ER degrader fulvestrant.

Incidence and Management of Diarrhea With Adjuvant Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.

Background: The APHINITY (BIG 4-11) study showed that pertuzumab significantly improved the rates of invasive disease-free survival among patients with human epidermal growth factor receptor 2 (HER2)-positive, operable breast cancer when added to adjuvant trastuzumab and chemotherapy. Because diarrhea was a common adverse event that could compromise treatment administration, we evaluated the incidence and management of diarrhea in the APHINITY study.

Patients And Methods: The APHINITY trial is a prospective, randomized, multicenter, multinational, double-blind, placebo-controlled trial.

Selective Inhibition of HDAC3 Targets Synthetic Vulnerabilities and Activates Immune Surveillance in Lymphoma.

mutations are highly recurrent in B-cell lymphomas and either inactivate its histone acetyltransferase (HAT) domain or truncate the protein. Herein, we show that these two classes of mutations yield different degrees of disruption of the epigenome, with HAT mutations being more severe and associated with inferior clinical outcome. Genes perturbed by mutation are direct targets of the BCL6-HDAC3 onco-repressor complex.

Author Correction: Tumour lineage shapes BRCA-mediated phenotypes.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Efficacy and Determinants of Response to HER Kinase Inhibition in -Mutant Metastatic Breast Cancer.

mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with -mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade.

A view on drug resistance in cancer.

The problem of resistance to therapy in cancer is multifaceted. Here we take a reductionist approach to define and separate the key determinants of drug resistance, which include tumour burden and growth kinetics; tumour heterogeneity; physical barriers; the immune system and the microenvironment; undruggable cancer drivers; and the many consequences of applying therapeutic pressures. We propose four general solutions to drug resistance that are based on earlier detection of tumours permitting cancer interception; adaptive monitoring during therapy; the addition of novel drugs and improved pharmacological principles that result in deeper responses; and the identification of cancer cell dependencies by high-throughput synthetic lethality screens, integration of clinico-genomic data and computational modelling.