Purpose: RNA splicing is a fundamental biological process that generates protein diversity from a finite set of genes. Recurrent somatic mutations of splicing factor genes are common in some hematologic cancers but are relatively uncommon in acute myeloid leukemia (AML, < 20% of patients). We examined whether RNA splicing differences exist in AML, even in the absence of splicing factor mutations. Experimental Design: We developed a bioinformatics pipeline to study alternative RNA splicing...
Wed Jul 15, 2020 10:05
Purpose: Patients with metastatic colorectal cancer refractory to chemotherapy have limited treatment options. Ensituximab (NEO-102) is a novel chimeric mAb targeting a variant of MUC5AC with specificity to colorectal cancer. Patients and Methods: Single-arm, phase II trial assessed the efficacy and safety of ensituximab in patients with advanced, refractory cancer who expressed MUC5AC antigen in tumor tissue. Ensituximab was administered intravenously every 2 weeks with 3 mg/kg as recommended...
Wed Jul 15, 2020 10:05
Purpose: Two studies in previously treated metastatic pancreatic cancer have been completed combining GVAX pancreas vaccine (GM-CSF–secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes–expressing mesothelin). In the current study, we compared Cy/GVAX followed by CRS-207 with (Arm A) or without nivolumab (Arm B). Patients and Methods: Patients with pancreatic adenocarcinoma who received one prior therapy for metastatic...
Wed Jul 15, 2020 10:05
Purpose: Cytomegalovirus (CMV) antigens occur in glioblastoma but not in normal brains, making them desirable immunologic targets. Patients and Methods: Highly functional autologous polyclonal CMV pp65-specific T cells from patients with glioblastoma were numerically expanded under good manufacturing practice compliant conditions and administered after 3 weeks of lymphodepleting dose-dense temozolomide (100 mg/m2) treatment. The phase I component used a 3+3 design, ascending through four...
Wed Jul 15, 2020 10:05
Purpose: Nintedanib enhances the activity of chemotherapy in metastatic non–small cell lung cancer (NSCLC). In this phase I/II study, we assessed safety and efficacy of nintedanib plus neoadjuvant chemotherapy, using major pathologic response (MPR) as primary endpoint. Patients and Methods: Eligible patients had stage IB (≥4 cm)–IIIA resectable NSCLC. A safety run-in phase was followed by an expansion phase with nintedanib 200 mg orally twice a day (28 days), followed by three cycles of...
Wed Jul 15, 2020 10:05
Purpose: TAK-659 is an investigational, dual SYK/FLT3 inhibitor with preclinical activity in B-cell malignancy models. This first-in-human, dose-escalation/expansion study aimed to determine the safety, tolerability, MTD/recommended phase II dose (RP2D), and preliminary efficacy of TAK-659 in relapsed/refractory solid tumors and B-cell lymphomas. Patients and Methods: Patients received continuous, once-daily oral TAK-659, 60–120 mg in 28-day cycles, until disease progression or unacceptable...
Wed Jul 15, 2020 10:05
Purpose: CPC634 is a novel nanoparticle entrapping docetaxel, developed to enhance the intratumoral chemotherapy exposure. This randomized cross-over study compared the intratumoral and plasma pharmacokinetics of CPC634 with conventional docetaxel. Patients and Methods: Adult patients with solid tumors were randomized to receive CPC634 (75 mg/m2) in cycle 1, and conventional docetaxel (75 mg/m2) in cycle 2 or vice versa. The study was powered to identify a 25% increase of intratumoral total...
Wed Jul 15, 2020 10:05
The adoptive transfer of genetically engineered chimeric antigen receptor (CAR) T cells has opened a new frontier in cancer therapy. Unlike the paradigm of targeted therapies, the efficacy of CAR T-cell therapy depends not only on the choice of target but also on a complex interplay of tumor, immune, and stromal cell communication. This presents both challenges and opportunities from a discovery standpoint. Whereas cancer consortia have traditionally focused on the genomic, transcriptomic, epigenomic,...
Wed Jul 15, 2020 10:05
Purpose: Apalutamide is a next-generation androgen receptor (AR) inhibitor approved for patients with nonmetastatic castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer. We evaluated the pharmacokinetics, safety, and antitumor activity of apalutamide combined with abiraterone acetate plus prednisone (AA-P) in patients with metastatic CRPC (mCRPC). Patients and Methods: Multicenter, open-label, phase Ib drug–drug interaction study conducted in 57...
Wed Jul 15, 2020 10:05
As the SARS-CoV-2 (COVID-19) pandemic spreads and the number of Bruton's tyrosine kinase inhibitor (BTKi)-treated COVID-19-affected patients grows, we must consider the pros and cons of BTKi discontinuation for our patients. In favor of BTKi continuation, BTK plays an active role in macrophage polarization. By modulating key transcription factors, BTK may regulate macrophage polarization downstream of classic M1 and M2 polarizing stimuli and mitigate the hyperinflammatory state associated with...
Wed Jul 15, 2020 10:05
Overall survival and disease-free survival have been the gold standard primary endpoints for neoadjuvant clinical trials. Major pathologic response is a clinically proven surrogate of efficacy and when used as the primary endpoint, can allow for more efficient evaluation of drugs in the neoadjuvant setting. See related article by Cascone et al., p. 3525
Wed Jul 15, 2020 10:05
Mutations in spliceosomal components are prevalent in myelodysplastic syndromes, but less so in acute myeloid leukemia (AML). However, aberrant splicing is prolific in AML, suggesting deregulated splicing could contribute broadly to tumorigenesis. Elevated stress responses correlate with splicing dysfunction across myeloid malignancies, representing potentially novel therapeutic targets. See related article by Anande et al., p. 3597
Wed Jul 15, 2020 10:05
Whether BTK inhibitors are effective when used after venetoclax in patients with chronic lymphocytic leukemia is an important unanswered question. In a large retrospective cohort study examining outcomes for next line treatment after venetoclax, BTK inhibitors were found to result in durable responses in patients who were not previously BTK inhibitor resistant. See related article by Mato et al., p. 3589
Wed Jul 15, 2020 10:05
Purpose: Patients with colorectal cancer with peritoneal metastases (CRPMs) have limited treatment options and the lowest colorectal cancer survival rates. We aimed to determine whether organoid testing could help guide precision treatment for patients with CRPMs, as the clinical utility of prospective, functional drug screening including nonstandard agents is unknown. Experimental Design: CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and...
Wed Jul 15, 2020 10:05
Purpose: Resistance to anti-PD1–based immune checkpoint blockade (ICB) remains a problem for the treatment of metastatic melanoma. Tumor cells as well as host myeloid cells can express the immune checkpoint ligand CD155 to regulate immune cell function. However, the effect of tumor CD155 on the immune context of human melanoma has not been well described. This observational study characterizes tumor CD155 ligand expression by metastatic melanoma tumors and correlates results with differences in...
Wed Jul 15, 2020 10:05
Purpose: One of the challenges of adoptive T cell therapy is the development of immune mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT).We aimed to identify factors that place patients at high risk of severe toxicity or treatment related death in a cohort of 75 patients with large B cell lymphoma treated with a standard of care CD19 targeted CAR T cell product (axicabtagene ciloleucel). Experimental Design: Serum cytokine and catecholamine levels were measured...
Wed Jul 15, 2020 16:05
Purpose: Ganetespib, a highly potent, small molecule Heatshock protein 90 inhibitor, has potential efficacy in malignant pleural mesothelioma (MPM) via activity on critical survival pathways and known synergies with antifolates and platinum chemotherapy. We conducted a dose-escalation study to identify the Maximum Tolerated Dose (MTD) of ganetespib in chemotherapy-naïve MPM patients. Experimental Design: MESO-02 (ClinicalTrials.gov: NCT01590160) was a non-randomized, multicentre, phase Ib trial...
Wed Jul 15, 2020 16:05
Purpose: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted Immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watch-and-Wait"). Experimental Design: Biopsies from two independent cohorts (n1=131, n2=118) of patients with LARC treated with nT followed by radical surgery, were immunostained for CD3+ and...
Wed Jul 15, 2020 16:05
Background Up to 17% of pancreatic cancer (PDAC) patients harbor pathogenic (germline or somatic) mutations in a homologous recombination, DNA damage response and repair (HR-DDR) gene, such as BRCA1/2, or PALB2. Platinum-based chemotherapy, or treatment with PARP inhibitors are of particular benefit in these patients. However, there may be even greater benefit when platinums and PARP inhibitors are combined. Patients and Methods We performed a single-arm, open-label, phase I/II study of the PARP...
Wed Jul 15, 2020 16:05
Purpose The prognosis for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is poor, and only a minority of patients benefit from checkpoint immunotherapy. Talimogene laherparepvec (T-VEC), an oncolytic immunotherapy approved for advanced melanoma, in combination with pembrolizumab may yield enhanced antitumor activity over either agent alone. Experimental Design This was a phase 1b/3, multicenter trial testing intratumoral T-VEC combined with intravenous pembrolizumab...
Wed Jul 15, 2020 16:05
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Multiple chemotherapeutic drugs have been tested to improve patient prognosis; however, the clinical efficacy of these treatments is low. One of the most controversial family of drugs are the proteasome inhibitors, which have displayed promising effects in pre-clinical studies, but low clinical performance. Here we unravel a specific transcriptomic signature that discriminates a subgroup of patients sensitive to the proteasome inhibitor...
Wed Jul 15, 2020 16:05
Purpose: TNF-related apoptosis inducing ligand (TRAIL) expression by immune cells contributes to anti-tumor immunity. A naturally occurring splice variant of TRAIL, called TRAILshort, antagonizes TRAIL-dependent cell killing. It is unknown whether tumor cells express TRAILshort and if it impacts anti-tumor immunity. Experimental Design: We used an unbiased informatics approach to identify TRAILshort expression in primary human cancers, and validated those results with immunohistochemistry (IHC) and...
Wed Jul 15, 2020 16:05
Abstract Purpose This open-label, dose-finding phase 1b/2 study reports the safety and activity of the first combination use with BRAF inhibitor (BRAFi) encorafenib plus MEK inhibitor (MEKi) binimetinib in patients with BRAF V600E-mutant solid tumors. (NCT01543698). Methods In phase 1, the recommended phase 2 doses (RP2D) were established (primary objective). In phase 2, the clinical activity of the combination at the RP2D was assessed (primary objective) in patients with BRAF-mutant metastatic colorectal...
Wed Jul 15, 2020 16:05
Publication date: Available online 14 July 2020Source: European Journal of CancerAuthor(s): Evangeline Samuel, Cherie Chiang, Ross Jennens, David Faulkner, Prudence A. Francis
Wed Jul 15, 2020 15:27
Publication date: Available online 15 July 2020Source: European Journal of Surgical OncologyAuthor(s): Kenichiro Furukawa, Satoshi Kamiya, Takashi Sugino, Daisuke Aizawa, Takanori Kawabata, Akifumi Notsu, Makoto Hikage, Yutaka Tanizawa, Etsuro Bando, Kohei Takizawa, Hiroyuki Ono, Masanori Terashima
Wed Jul 15, 2020 18:23
Future Oncology, Ahead of Print.
Wed Jul 15, 2020 11:49
Related Articles Real-world osimertinib for EGFR mutation-positive non-small-cell lung cancer with acquired T790M mutation. Future Oncol. 2020 Jul 14;: Authors: Imamura F, Kimura M, Yano Y, Mori M, Suzuki H, Hirashima T, Ihara S, Komuta K, Shiroyama T, Nagatomo I, Kumagai T Abstract Aim: Osimertinib is a key drug for EGFR mutation-positive non-small-cell lung cancer (NSCLC). As the hazards ratio of overall survival in comparison with first-generation...
Wed Jul 15, 2020 17:26
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
Mon Jul 13, 2020 10:00
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
Mon Jul 13, 2020 10:00
The original version of this article unfortunately contained a mistake. The name of “Carolina Ledsham” is now corrected in the author group of this article.
03:42
Abstract This piece reflects on an innovative project that we undertook: interviewing master physicians across the world of oncology and asking them what was their secret to success. It provides insights into the answers received from over fifty interviews and the process that was followed.
03:42
Abstract The early diagnosis of cutaneous melanoma provides less aggressive treatment reducing mortality. General practitioners are responsible for cancer diagnoses in the Brazilian Public Health System and therefore play a crucial role in the prevention and early detection of melanoma. To assess the melanoma knowledge of a primary healthcare physician, the general practitioner, compared to a dermatologist. General practitioners and dermatologists answered a questionnaire about...
03:42
First generation antibody drug conjugates (ADCs) are heterogeneous mixtures that have shown clinical benefit, but generally exhibited safety issues and a narrow therapeutic window due in part to off-target toxicity caused by ADC instability. ARX788 is a next generation, site-specific anti-HER2 ADC that utilizes a unique non-natural amino acid enabled conjugation technology and a non-cleavable Amberstatin (AS269) drug-linker to generate a homogeneous ADC with a drug-to-antibody ratio of 1.9. ARX788...
Wed Jul 15, 2020 16:15
We previously reported that silencing of the PRR gene, which encodes the (pro)renin receptor ((P)RR) significantly reduced Wnt/β-catenin-dependent development of pancreatic ductal adenocarcinoma (PDAC). Here, we examined the effects of a panel of blocking monoclonal antibodies (mAbs) directed against the (P)RR extracellular domain on proliferation of the human PDAC cell lines PK-1 and PANC-1 in vitro and in vivo. We observed that four rat anti-(P)RR mAbs induced accumulation of cells in the G0/G1...
Wed Jul 15, 2020 16:15
Antibody drug conjugates (ADCs) containing pyrrolobenzodiazepine (PBD) dimers are being evaluated clinically in both hematological and solid tumors. These include ADCT-301 (camidanlumab tesirine) and ADCT-402 (loncastuximab tesirine) in pivotal Phase 2 trials that contain the payload tesirine which releases the PBD dimer warhead SG3199. An important consideration in future clinical development is acquired resistance. The aim was to generate and characterize PBD acquired resistant cell lines in both...
Wed Jul 15, 2020 16:15
Abstract Although papillary endothelial hyperplasia may occur at almost any site, one of the most common sites is the hand. It is generally regarded as a reactive vascular proliferation i.e. exuberant form of organizing thrombus. Diagnosis of Masson tumor can be challenging due to its close clinical, radiological and even histopathological resemblance to angiosarcoma. We present seven cases of Masson tumor of the hand; wanting to reveal its nature using new vascular markers and...
Wed Jul 15, 2020 03:00
Lentigo maligna (LM) is the most common subtype of in situ melanoma und occurs frequently in the sun-exposed head and neck region in elderly patients. The therapeutic “gold standard” is surgical excision, as t...
Tue Jul 14, 2020 03:00
The use of stereotactic body radiotherapy (SBRT) as the primary treatment modality in clinically localized prostate cancer (PCa) is emerging. The aim of the study was to analyze the long-term results of PCa pa...
Tue Jul 14, 2020 03:00
We would like to thank Dr Leung for his appreciation on our manuscript exploring the role of personality traits on the professional quality of life of radiation oncologists, with a targeted focus on alexithymia and empathy [1,2]. Indeed, with our study we tried to provide insights on inherent individual factors having an impact on the well-being at work in radiation oncology. As pointed out by Dr Leung, professional satisfaction is a multifactorial set of instances pertinent to individual, environmental...
Wed Jul 15, 2020 03:00
Pancreatic Adenocarcinoma is associated with high mortality and shows increasing incidence in most countries [1,2]. In recent years, advances concerning cancer-specific outcome have been minimal, with 5-year overall survival (OS) rates below 10% [1]. Surgery, as a treatment of choice, leads to 5-year OS rates up to 20-25%; nevertheless, a large fraction of patients is unfit for surgery at diagnosis due to disease stage or other concomitant exclusion criteria [3]. In fact, the majority of patients...
Wed Jul 15, 2020 03:00
Radiation-induced lymphopenia is associated with poor prognosis in resected pancreatic cancer and locally advanced pancreatic cancer. However, whether lymphocyte recovery contributes to pancreatic cancer prognosis has not been well-investigated.
Wed Jul 15, 2020 03:00
Publication date: October 2020Source: Cancer Epidemiology, Volume 68Author(s): Keming Yang, Michele R. Forman, Brett H. Graham, Patrick O. Monahan, Edward L. Giovannucci, Immaculata De Vivo, Andrew T. Chan, Hongmei Nan
Wed Jul 15, 2020 12:52
Publication date: August 2020Source: Cancer Epidemiology, Volume 67Author(s): TienYu Owen Yang, Kuan-Ying Arthur Huang, Mei-Huei Chen, Pau-Chung Chen, Wan-Ting Huang
Wed Jul 15, 2020 12:52
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου
Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.