Ablation plus chemoembolization equals success
Sometimes the patient presents with more than one problem, such as when diagnosed with primary liver cancer with hepatic vein tumor thrombosis (HVTT), a combination that offers a very poor prognosis, indeed. Researchers in China revisited patient data drawn from 26 cases at a single center from 2011 to 2016 in an effort to determine the efficacy of percutaneous thermal ablation combined with transarterial chemoembolization (TACE) in contrast to TACE alone, with the two different approaches applied to 13 patients each. The patients undergoing the dual treatment plan enjoyed a median survival of 18 months, nearly thrice the 6.5 months seen in the patients on TACE alone. The dual-treatment arm demonstrated one-year survival of nearly 57 percent and three-year survival of 47 percent, while only 10.9 percent of the TACE-only group made it to one year. Among the factors that were associated with survival were differences in ablation technique and the presence of extrahepatic metastases and lymph node metastases. The authors concluded that for patients with primary liver cancer and HVTT, the combination therapy not only offers greater survival than TACE alone, but also that long-term survival "could be achieved in selected patients." The article appears in the July 31, 2018, issue of PLOS One under the title "Percutaneous thermal ablation combined with TACE versus TACE monotherapy in the treatment for liver cancer with hepatic vein tumor thrombus: A retrospective study."
Ignoring mutation and targeting inflammation
The gene STK11 encodes the tumor suppressor liver kinase B1, and STK11 mutations promote Peutz-Jeghers syndrome (PJS), a cancer predisposition syndrome. Individuals with PJS are prone to developing gastrointestinal polyps, which can lead to gastrointestinal (GI) tumors. Researchers from the Van Andel Research Institute and the Canadian McGill University have shown that STK11 mutations led to increased inflammation, and that targeting the inflammation could improve outcomes in mouse models of PJS. The team showed that while STK11 mutations in intestinal epithelial cells did not increase polyp formation in a mouse model of PJS, mutations in T cells led to the activation of pro-inflammatory transcription and chronic inflammation. Targeting either T cells or the pro-inflammatory signals STAT3 and interleukin-6 reduced poly formation. More than 90 percent of PJS patients develop GI tumors by age 65, and the authors suggested that "targeting chronic GI inflammation may present a novel approach to reducing disease incidence and polyp burden in PJS patients." Their work appeared in the July 27, 2018, issue of Science.
Predicting chemotherapy synergies
Keeping its DNA in working order is a priority for any cell, and the response repertoire to DNA damage is correspondingly complex, encompassing dozens of genes in multiple pathways. Some chemotherapy drugs work by inducing DNA damage, and preventing DNA repair is one possible way to improve their efficacy. A team from Merrimack Pharmaceuticals Inc. has developed a computational model to predict the specific DNA damage repair pathways that would be engaged after different chemotherapies, and they validated their findings experimentally. The authors wrote that "computational models such as the one presented here can be used to understand the molecular basis that defines the complex interplay between cell survival and cell death and to rationally identify chemotherapy-potentiating drug combinations," potentially improving the success rate of clinical trials of such combinations. The team reported its results in the July 24, 2018, issue of Science Signaling.
Phase II study backs TTF plus paclitaxel
Oncology has become more familiar over the years with the use of combination therapies, and Novocure of St. Helier, Jersey, reported that the phase II pilot study of the company's TTF (Tumor Treating Fields) along with paclitaxel more than doubled progression-free survival in women with ovarian cancer. The results of the study, which appeared in Gynecologic Oncology, include that the median time to progression-free survival for the 31 patients on the dual therapy was 8.9 months, more than double the 3.9 months in historical controls treated with paclitaxel alone. While median overall survival has not yet been reached, median one-year survival in the device/drug group was 61 percent. Ignace Vergote, an investigator in the study and the chair of obstetrics and gynecology at the Catholic University of Leuven, Belgium, said the data demonstrate that the combination "has the potential to increase survival without significantly increasing side effects for recurrent ovarian cancer patients." The article is in August issue of in Gynecologic Oncology under the title, "Tumor Treating Fields in combination with paclitaxel in recurrent ovarian carcinoma: Results of the INNOVATE pilot study."
Timothy Leary approach to cancer
Psychologist Timothy Leary was well known for having advised a Senate panel to try LSD as a way to achieve a more Zen state of mind, but a recent article in Nature Communications suggests acid isn't so good for tumors. Researchers in Israel and the U.S. examined the question of the role of pH in the intra-tumor environment in an in-silico experiment, and demonstrated that higher pH levels boosted tumor viability. Conversely, a more acidic environment inside tumors seemed to tamp down on breast cancer cells – particularly the more aggressive types – in their virtual experiment. The article appears in the July 31, 2018, online issue of Nature Communications under the title "Systems analysis of intracellular pH vulnerabilities for cancer therapy."