“The genetic mutations underlying treatment resistance in non-small cell lung cancer (NSCLC) are more complex and dynamic than previously thought. Analysis of 355 biopsied tumors from patients who acquired resistance to EGFR inhibitors, the most common form of targeted therapy for NSCLC, found that mutations frequently varied between biopsies and that nearly one in five patients harbored more than one type of genetic resistance to treatment. Findings will be presented today at the 2017 Multidisciplinary Thoracic Cancers Symposium.”
“Results from a large clinical study showed that testing pediatric brain tumors for genetic abnormalities is feasible and could play a role in guiding patients’ treatment.
“The study, published in Neuro-Oncology, showed that more than half of the samples taken from pediatric brain tumors and analyzed using genomic profiling had genetic irregularities that could influence how the disease was diagnosed or treated with approved drugs or agents being evaluated in clinical trials.”
“The addition of a targeted agent to endocrine therapy for metastatic breast cancer led to unprecedented improvement in progression-free survival (PFS) that will have a ‘paradigm changing’ effect on clinical management, an investigator said here.
“Patients who received the cyclin-dependent kinase (CDK)4/6 inhibitor ribociclib in addition to letrozole (Femara) had a 44% reduction in the PFS hazard compared with patients treated with letrozole alone. The median PFS (primary endpoint) was 14.7 months with letrozole but had yet to be reached with letrozole plus ribociclib, ‘but it is expected to far exceed what the control arm did,’ Gabriel N. Hortobagyi, MD, reported at the European Society for Medical Oncology (ESMO) conference.”
“The FDA has approved atezolizumab (Tecentriq) for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) who have progressed after a platinum-containing regimen and an FDA-approved targeted therapy for those patients harboring EGFR or ALK abnormalities.
“The approval is based on multiple clinical trials, the largest being the phase III OAK trial, which was presented at the 2016 ESMO Congress. In the study, atezolizumab reduced the risk of death by 26% compared with docetaxel in patients with advanced NSCLC following the failure of platinum-based chemotherapy. The median overall survival (OS) was improved by 4.2 months with the PD-L1 inhibitor versus chemotherapy. The survival benefit with atezolizumab was observed regardless of PD-L1 status or histology.”
“The promise of personalized cancer medicine is still a long way off, and it’s questionable whether any personalized approach will ever benefit patients to any significant degree, say two researchers writing in a “sounding board” article published online September 29 in the New England Journal of Medicine.
” ‘Patients love the idea that they have a specific mutation in their tumour and that if they have their cancer gene sequenced, there will be a specific and effective drug that targets their mutation,’ coauthor Ian Tannock, MD, PhD, Princess Margaret Cancer Center and the University of Toronto, Ontario, Canada, toldMedscape Medical News in an email.”
“Brain metastases are one of the most common complications of advanced melanoma, requiring multidisciplinary management. Patients who are diagnosed with these metastases have an expected median survival of only 4 to 5 months. Moffitt Cancer Center researchers hope to improve these survival rates following a new study in Annals of Oncology that shows novel immune and targeted therapies with radiation therapy improves the outcomes of patients with melanoma brain metastases over conventional chemotherapy.”
“The loss of CHD1, one of the most frequently mutated genes in prostate tumors, sensitizes human prostate cancer cells to different drugs, including PARP inhibitors. This suggests CHD1 as a potential biomarker for targeted prostate cancer therapy. These are the results of a study published in EMBO Reports.
“A team of researchers in Germany and Denmark led by Steven Johnsen, Professor at the University Medical Center Göttingen, Germany, used human prostate cancer cell lines and depleted them of the DNA-binding protein CHD1. The CHD1 gene is mutated in 15-27% of all prostate tumors, and such mutations correlate with chromosomal instability and poor prognosis for prostate cancer patients. The researchers could demonstrate that CHD1-depleted cells have defects in homologous recombination (HR), an important mechanism for repairing breaks in the DNA molecule. The data indicate that CHD1’s normal function is the loosening of DNA around break sites in order to facilitate the access of HR repair proteins. Importantly, like cancer cells with other mutations in the HR repair pathway, CHD1-depleted prostate cancer cells proved to be hypersensitive to chemotherapeutic drugs causing DNA breaks, such as Mitomycin C, Irinotecan and PARP inhibitors.”
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As always, the more new treatments become available in melanoma, the more new challenges arise. With eight new drugs approved for melanoma in the last five years, oncologists may sometimes face the difficult choice of what drugs to choose for a patient’s first-line treatment. Immune checkpoint drugs sometimes cause serious side effects, but progress is being made on how to treat these and also how to treat patients with pre-existing autoimmune conditions. New approaches are needed in efforts to prevent recurrence of melanomas diagnosed at earlier stages of disease progression. These and other challenges are discussed below. Continue reading…