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Clinical development of new treatment options for patients with pancreatic cancer has been slow and expensive and resulted in few effective therapies. With a dismal five-year survival rate of 11% in the U.S., pancreatic cancer remains the third leading cause of cancer-related deaths and is poised to move to second by 2030. Standard clinical trials typically compare one investigational treatment to one standard of care, encompass one phase of clinical investigation at a time, and treat one patient population. Accrual and data analysis are often very slow, and unfortunately, the vast majority of clinical trials targeting pancreatic cancer patients are unsuccessful. More efficient clinical trial designs can include combining phases I and II or phases II and III, and trials that involve a master protocol approach can also answer multiple clinical questions simultaneously. These modern clinical trial designs can allow a faster, more efficient and cost-effective approach to testing investigational therapies in patients with pancreatic cancer and, most importantly, fewer patients may be required to determine the efficacy of treatment. Herein we summarize some of the recent innovative clinical trials in pancreatic cancer to provide meaningful data toward developing new treatment options to benefit patients with a dismal disease like pancreatic cancer. LESS      Full article

Radiological imaging has a critical role in the diagnosis of sarcomas and in evaluating therapy response assessment. The current gold standard for response assessment in solid tumors is the Response Evaluation Criteria in Solid Tumors, which evaluates changes in tumor size as a surrogate endpoint for therapeutic efficacy. However, tumors may undergo necrosis, changes in vascularization or become cystic in response to therapy, with no significant volume changes; thus, size assessments alone may not be adequate. Such morphological changes may give rise to radiographic phenotypes that are not easily detected by human operators. Fortunately, recent advances in high-performance computing and machine learning algorithms have enabled deep analysis of radiological images to extract features that can provide richer information about intensity, shape, size or volume, and texture of tumor phenotypes. There is growing evidence to suggest that these image-derived or “radiomic features” are sensitive to biological processes such as necrosis and glucose metabolism. Thus, radiomics could prove to be a critical tool for assessing treatment response and may present an integral complement to existing response criteria, opening new avenues for patient assessment in sarcoma trials. LESS      Full article

Malignant pleural mesothelioma (MPM) is an aggressive and rare disease, mainly due to asbestos exposure, characterized by a poor prognosis. For almost two decades, platinum-based chemotherapy has been the only approved therapeutic regimen for first-line MPM, with an overall survival of 12 months. In the last years, the therapeutic scenario of different tumor types, including MPM, has dramatically changed due to immune checkpoint inhibition. The promising results of this approach have promoted new efforts into clinical research, and many trials investigating novel therapeutic combinations are currently ongoing. The aim of the present review is to provide a comprehensive overview of the most promising immunotherapeutic-based strategies currently under investigation for advanced MPM. LESS      Full article

This review provides an overview of articles about peritoneal mesothelioma (PM) to analyze the effect of treatment modalities on response rates, post-treatment side effects, morbidity and mortality, and survival. Median survival in months following systemic chemotherapy (SC) ranged from 8.7 to 26.8 months. However, no patient was reported to have survived for more than five years with SC alone. In contrast, comprehensive treatment that included cytoreductive surgery (CRS) + perioperative chemotherapy (POC) showed a significantly longer median survival time than SC alone. Additionally, CRS + POC demonstrated 10-year survival rates of 12%-35%. Accordingly, CRS + POC is an innovative treatment that provides long-term survival in selected patients with PM. Selection criteria are performance status (ECOG PS ≤ 1), the absence of extraperitoneal metastasis, PCI less than cutoff levels (from < 10 to < 28), MIB-1 index (< 10), and histologic type (epithelioid type). Postoperative morbidity and mortality rates after CRS + POC were significantly higher than with more conventional operations. Accordingly, CRS and POC should be done at the specialized peritoneal surface malignancy centers. LESS      Full article

Over the past decade, researchers have identified and characterized the diverse cell populations within the tumor microenvironment of pancreatic cancer. The interplay between these cells in the TME either promotes or inhibits the malignant behavior of pancreatic cancer cells. Cancer-associated fibroblasts, previously thought to be one main subset, can now be broadly subclassified into three main types: inflammatory, myofibroblastic, and antigen-presenting, with the former and the latter two exerting pro-tumoral and anti-tumoral functions, respectively. Myeloid cells include myeloid-derived suppressor cells and tumor-associated macrophages. Myeloid-derived suppressor cells can be further divided into polymorphonuclear and monocytic and exhibit pro-tumoral activities. Tumor-associated macrophages exhibit M1 (anti-tumoral) or M2 (pro-tumoral) phenotypes, which are present in a dynamic fashion between the two phenotypes. Other constituents of the immune make-up of the tumor microenvironment include T and B cells and less described subsets which include natural killer cells, γδ T cells, and group 2 innate lymphoid cells. This review provides an overview of the studies that lead to the discovery of those cellular populations and highlights the recent efforts to utilize them as therapeutic targets in pancreatic cancer. LESS      Full article

Telemedicine is being incorporated into routine healthcare, including oncology. The integration of telemedicine with patient electronic medical records and the adoption of virtual provider-patient encounters was accelerated by the SARS-CoV2 worldwide pandemic. Although telemedicine has existed for more than 50 years, the impact of telemedicine on patient care and health outcomes is relatively understudied, and little research has been conducted on telehealth in the care of patients with sarcoma. This review discusses the potential applications of telemedicine to the care of patients with sarcoma and some of the data available on patient and provider preferences for telemedicine vs. in-person healthcare encounters. Some of the areas of care in which greater adoption of telemedicine may be beneficial to patients with sarcoma are also discussed. LESS      Full article

Aberrant activation of signal transducer and activator of transcription (STAT) proteins is associated with the development and progression of solid tumors. However, as transcription factors, these proteins are difficult to target directly. In this review, we summarize the role of targeting Janus kinases (JAKs), upstream activators of STATs, as a strategy for decreasing STAT activation in solid tumors. Preclinical studies in solid tumor cell line models show that JAK inhibitors decrease STAT activation, cell proliferation, and cell survival; in in vivo models, they also inhibit tumor growth. JAK inhibitors, particularly the JAK1/2 inhibitor ruxolitinib, sensitize cell lines and murine models to chemotherapy, immunotherapy, and oncolytic viral therapy. Ten JAK inhibitors have been or are actively being tested in clinical trials as monotherapy or in combination with other agents in patients with solid tumors; two of these inhibitors are already Food and Drug Administration (FDA) approved for the treatment of myeloproliferative disorders and rheumatoid arthritis, making them attractive agents for use in patients with solid tumors as they are known to be well-tolerated. Four JAK inhibitors (two of which are FDA approved for other indications) have exhibited promising anti-cancer effects in preclinical studies; however, clinical studies specifically assessing their activity against the JAK/STAT pathway in solid tumors have not yet been conducted. In summary, JAK inhibition is a viable option for targeting the JAK/STAT pathway in solid tumors and merits further testing in clinical trials. LESS      Full article

Cancer is not just a lump of cells that divide, invade, and spread randomly, but rather a multi-layered precisely tuned process that requires the participation of the whole organism. There is an urgent need to zoom-out from the cellular and the local stromal view and broaden our perspective by including the whole organism level. Geographically separated cancer tissues communicate between themselves, forming a system that interacts with the rest of the organism through cancer induced systemic pathogenic networks. In the present paper, I introduce six systemic hallmarks of cancer that emerge as a result of these interactions. I also describe several potential therapeutic approaches that can be developed using the cancer system concept. Overall, I argue that the tumoricentric paradigm should be replaced with a broader approach that brings into focus the “cancerized” organism. LESS      Full article

The discovery that all cells secrete extracellular vesicles (EVs) to shuttle proteins and nucleic acids to recipient cells suggested they play an important role in intercellular communication. EVs are widely distributed in many body fluids, including blood, cerebrospinal fluid, urine and saliva. Exosomes are nano-sized EVs of endosomal origin that regulate many pathophysiological processes including immune responses, inflammation, tumour growth, and infection. Healthy individuals release exosomes with a cargo of different RNA, DNA, and protein contents into the circulation, which can be measured non-invasively as biomarkers of healthy and diseased states. Cancer-derived exosomes carry a unique set of DNA, RNA, protein and lipid reflecting the stage of tumour progression, and may serve as diagnostic and prognostic biomarkers for various cancers. However, many gaps in knowledge and technical challenges in EVs and extracellular RNA (exRNA) biology, such as mechanisms of EV biogenesis and uptake, exRNA cargo selection, and exRNA detection remain. The NIH Common Fund-supported exRNA Communication Consortium was launched in 2013 to address major scientific challenges in this field. This review focuses on scientific highlights in biomarker discovery of exosome-based exRNA in cancer and its possible clinical application as cancer biomarkers. LESS      Full article

Pancreatic ductal adenocarcinoma (PDAC) remains a disease with a dismal prognosis. Since 1996 there have only been two upfront regimens found to be superior to gemcitabine: FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin), and gemcitabine plus nab-paclitaxel. Despite the improvement noted in these trials, PDAC is highly chemo-resistant and patients who respond will inevitably develop resistance. The unique immunosuppressive tumor microenvironment with extensive desmoplasia has posed challenges to developing new and effective treatments. Therapeutic vaccines, combination treatments, adoptive T cell transfer, as well as immunomodulators are being explored. With the emerging use of immunotherapy and immunomodulators, the scope of this review is to present the current data on these agents as well as focus on the advancements in the treatment of PDAC. Overall, results in this realm have been disappointing to date reflecting the non-immunogenic and complex tumor microenvironment of PDAC. LESS      Full article