Cancers, Vol. 11, Pages 1502: Endoplasmic Reticulum Stress Signaling as a Therapeutic Target in Malignant Pleural Mesothelioma

Cancers, Vol. 11, Pages 1502: Endoplasmic Reticulum Stress Signaling as a Therapeutic Target in Malignant Pleural Mesothelioma Cancers doi: 10.3390/cancers11101502 Authors: Xu Yang Yang Berezowska Gao Liang Marti Hall Dorn Kocher Schmid Peng Malignant pleural mesothelioma (MPM) is a lethal cancer with limited treatment options. No targeted therapy has emerged yet. Here, we performed an integrated molecular characterization of patient tumors in the TCGA dataset, and discovered that endoplasmic reticulum (ER) stress and the adaptive unfolded protein response (UPR) signaling are characteristically deregulated in MPM. Consequently, pharmacological perturbation of ER stress/UPR axis by HA15, an agent that induces persistent proteotoxic stress in the ER, selectively suppresses the viability of MPM cells including those refractory to standard chemotherapy. Mechanically, HA15 augments the already high basal level of ER stress in MPM cells, embarks pro-apoptotic malfunctional UPR and autophagy, which eventually induces cell death in MPM. Importantly, HA15 exerts anti-MPM effectiveness in a mouse model of patient-derived xenografts (PDX) without eliciting overt toxicity when compared to chemotherapy. Our results revealed that programs orchestrating ER stress/UPR signaling represent therapeutic vulnerabilities in MPM and validate HA15 as a promising agent to treat patients with MPM, naïve or resistant to chemotherapy.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

Related Links:

The Miami Cancer Institute on Thursday will begin using the innovative Tumor Treating Fields device for patients with malignant pleural mesothelioma. It is the first new treatment approved for mesothelioma by the U.S. Food and Drug Administration in more than 15 years. “This is actually pretty exciting for us,” Dr. Rupesh Kotecha, the radiation oncologist who will oversee the treatment protocol in Miami, told The Mesothelioma Center at Asbestos.com. “It’s another tool in our armamentarium. It’s something we can offer patients that has shown a real benefit.” The noninvasive Tumor Treating...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Although malignant mesothelioma (MM) is rare among thoracic malignancies, approximately 1500 and 3000 patients are newly diagnosed each year in Japan and the United States [1], respectively. Treatment of MM, including surgery, radiotherapy, and chemotherapy, is recommended according to stage, performance status, pulmonary function, complications, and patient preference. First-line chemotherapy for advanced MM involves a combination of cisplatin and pemetrexed as the standard treatment. Although this combination has been proven to prolong survival over cisplatin alone in a phase III trial (12.1 months vs.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Dr. Giovanni Ceresoli doesn’t think Tumor Treating Fields will work for every patient with mesothelioma cancer, but he knows it will work for some. They are in his clinic. As the principal investigator of the multicenter clinical trial that led to approval by the U.S. Food and Drug Administration in May, Ceresoli has played a major role in the development of this latest mesothelioma treatment. “It might be too early to say this is a major breakthrough — we need more data — but I hope it is. I know it’s something promising, very promising,” Cerosoli told The Mesothelioma Center at Asbest...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Doctors at the Swiss Group for Clinical Cancer Research in Zurich, Switzerland, have uncovered a novel, anti-tumor compound that could become a needed second-line treatment for pleural mesothelioma cancer. Their recent multicenter phase II clinical trial conducted in Switzerland and Italy revealed the safety and efficacy of lurbinectedin, a synthetically produced agent that inhibits the growth of mesothelioma cells. “We believe this could represent a new treatment option for pleural mesothelioma,” Dr. Yannis Metaxas, oncologist at Kantonsspital Graubunden outside Zurich, told The Mesothelioma Center at Asbestos...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Peritoneal mesothelioma of both borderline and malignant subtypes can be successfully managed with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The incidence of diffuse malignant peritoneal mesothelioma has statistically increased over time in Sweden; fortunately likewise, the overall survival has also increased statistically in part due to the implementation of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. AbstractThe study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Conclusion: This is the first description of gC1qR expression in MPM. The data identify gC1qR as a potential new prognostic factor in patients treated with surgery and chemotherapy.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Results from a phase III clinical trial comparing Keytruda (pembrolizumab) to standard chemotherapy shows the immunotherapy drug still has a long way to go as a viable treatment option for malignant pleural mesothelioma. Keytruda did not improve progression-free survival for mesothelioma patients who progressed after first-line chemotherapy. The disappointing results from the PROMISE-meso study were presented at the European Society of Medical Oncology (ESMO) annual meeting last week. It was the first randomized trial comparing progression-free survival between immunotherapy and first-line chemotherapy for mesothelioma p...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
AbstractMalignant peritoneal mesothelioma (MPeM) is a rare and aggressive form of malignant mesothelioma. Sufficient biological tools for studying the functional characteristics of this cancer have not been developed. Therefore, in this study, a novel human cancer cell line, KOG-1, was established from ascites fluids isolated from a 39-year-old Japanese woman with pemetrexed-resistant MPeM. Cells were dendritic or linear immediately after thawing, showed a jigsaw puzzle-like and spindle arrangement during growth, and formed monolayers without contact inhibition in two-dimensional (2D) culture. The population doubling time ...
Source: Human Cell - Category: Cytology Source Type: research
A mesothelioma patient at West Cancer Center in Memphis, Tennessee, is the first in the country to use NovoTTF-100L, a noninvasive electric therapy treatment, since its approval by the U.S. Food and Drug Administration in May. The FDA’s approval of Novocure’s Tumor Treating Fields device for the treatment of mesothelioma marked the first new FDA-approved treatment option for the rare asbestos-related cancer in more than 15 years. NovoTTF-100L uses a low-voltage electrical field that is distributed with three pads attached to the front and back of a person’s chest. The electrical current is designed to di...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
We examined whether switch maintenance gemcitabine in patients, who did not show progression after first-line platinum-pemetrexed, could prolong time to disease progression.MethodsNVALT19 was an open label, randomized phase II trial, conducted in The Netherlands. Main eligibility criteria were pathologically proven MM, ECOG-PS 0-2 and completion of 4-6 cycles of first-line platinum-pemetrexed without progression. Patients were randomized 1:1 between gemcitabine (1250  mg/m2 day 1 and 8 of 3 weekly schedule) or best supportive care (BSC). Gemcitabine was given until disease progression, severe toxicity or pati...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
More News: Asbestosis | Cancer | Cancer & Oncology | Chemotherapy | Mesothelioma | Toxicology