Cancers Evade Immunotherapy by ‘Discarding the Evidence’ of Tumor-Specific Mutations

Excerpt:

“Results of an initial study of tumors from patients with lung cancer or head and neck cancer suggest that the widespread acquired resistance to immunotherapy drugs known as checkpoint inhibitors may be due to the elimination of certain genetic mutations needed to enable the immune system to recognize and attack malignant cells. The study, conducted by researchers on the cells of five of their patients treated at the Johns Hopkins Kimmel Cancer Center, is described online Dec. 28 in Cancer Discovery.”

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Significant Survival Gains with Atezolizumab vs Docetaxel for Non-Small-Cell Lung Cancer

Excerpt:

“The first phase III study of PD-L1 inhibitor atezolizumab in previously-treated non-small-cell lung cancer has seen significant improvements in survival compared to standard chemotherapy, researchers reported at the ESMO 2016 Congress in Copenhagen.

“PD-L1 inhibitors are of a class of cancer immunotherapies called checkpoint inhibitors, and work by inhibiting one of the mechanisms of resistance developed by cancer cells in order to evade the immune system.”

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Scientists Find Lethal Vulnerability in Treatment-Resistant Lung Cancer

Excerpt:

“Researchers working in four labs at UT Southwestern Medical Center have found a chink in a so-called ‘undruggable’ lung cancer’s armor — and located an existing drug that might provide a treatment.

“The study, published this week in Nature, describes how the drug Selinexor (KPT-330) killed lung cancer cells and shrank tumors in mice when used against cancers driven by the aggressive and difficult-to-treat KRAS cancer gene. Selinexor is already in clinical trials for treatment of other types of cancer, primarily leukemia and lymphoma but also gynecological, brain, prostate, and head and neck cancers.”

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Here Are Some Ways Cancer Can Thwart the New Immunotherapy Drugs

Excerpt:

“A new type of cancer drug designed to unleash the immune system is revolutionizing treatment for advanced melanoma, lung cancer and other malignancies. But some patients who initially respond to the therapy relapse, and researchers are anxious to figure out how and why the delayed resistance occurs.

” ‘Does the immune system stop working, or does the cancer change so that it’s no longer responding to the immune system?’ said Antoni Ribas, director of the Jonsson Comprehensive Cancer Center Tumor Immunology Program at the University of California at Los Angeles.

“New research by Ribas and others, published online Wednesday in the New England Journal of Medicine, provides some answers. The study, which outlines key mechanisms in how melanoma becomes resistant to immunotherapy, found that genetic changes in tumors allowed them to avoid recognition by the immune system or become less sensitive to its attacks.”

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Moffitt Researchers Develop a Novel Cancer Treatment Approach Based on Evolutionary Principals to Inhibit Chemo-Resistance, Prolong Progression-Free Survival

“Despite numerous advances in oncology since the War on Cancer began, many patients develop resistance to standard therapies and eventually relapse. Moffitt Cancer Center researchers hope to improve treatment outcomes with development of a novel therapeutic strategy, called adaptive therapy, which is based on evolutionary principals and aims to keep resistant cells in check by maintaining a population of chemo-sensitive cells.

“The standard strategy for administering cancer chemotherapy has changed very little over the past five decades.  Cancer drug are typically given at the maximum tolerated dose that a patient can tolerate without any life-threatening toxicity.  While this strategy works very effectively at killing cancer cells in the short-term, once the chemo-sensitive cells are removed, existing chemo-resistant cells survive and then continue to grow and divide despite the ongoing therapy.”


Blood Test Picks out Prostate Cancer Drug Resistance

“Scientists have developed a blood test that can identify key mutations driving resistance to a widely used prostate cancer drug, and identify in advance patients who will not respond to treatment.

“The new research paves the way for information from a  to inform  in future, with only those  whose cancers are free of resistance mutations taking the drug, abiraterone.

“The study is also a proof of principle that tests for cancer DNA in the bloodstream can be used to detect  – allowing patients who will not benefit from one drug to be given an alternative treatment instead.

“Researchers at The Institute of Cancer Research, London, the Royal Marsden NHS Foundation Trust, and the University of Trento, Italy, analysed 274 blood samples from 97 patients using state-of-the-art DNA sequencing techniques.

“They found that mutations in a gene called the androgen receptor (AR) predicted resistance to the prostate cancer drug abiraterone, and that patients with these mutations had poorer survival.”


Alectinib Promising in ALK-Positive Advanced NSCLC

“The ALK and RET inhibitor alectinib yielded good response rates and was very well tolerated in a phase II trial of patients with advanced, ALK-positive non–small-cell lung cancer (NSCLC; abstract 8008). Results were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 to June 2, in Chicago.

“Crizotinib is currently the standard-of-care for advanced, treatment-naive ALK-positive NSCLC. ‘However, the median progression-free survival (PFS) for these patients on crizotinib is under 12 months,’ said Sai-Hong Ignatius Ou, MD, PhD, of the UC Irvine Medical Center in California. ‘This is in part due to development of ALK mutations that are resistant to crizotinib.’

“Alectinib is a next-generation inhibitor that is highly selective for ALK and RET; as an ALK inhibitor, Ou said, it is approximately five times as potent as crizotinib. It can inhibit the majority of clinically relevant acquired ALK mutations.”


Clovis Oncology's Rociletinib (CO-1686) Phase 2 Study Results Demonstrate Consistent and Promising Clinical Activity and Disease Control in Very Advanced Patients with EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)

“Clovis Oncology (NASDAQ:CLVS) announced today updated findings from its Phase 2 clinical study of rociletinib (CO-1686), the Company’s novel, oral, targeted covalent (irreversible) mutant-selective inhibitor of the epidermal growth factor receptor (EGFR) for the treatment of non-small cell lung cancer (NSCLC) in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. These data from the TIGER-X trial are being presented today in an oral presentation (Abstract #8001) at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

“ ‘The maturing data for rociletinib confirm in a large patient population what we have seen in our early clinical experience,’ said Jonathan Goldman, MD, TIGER-X investigator and Assistant Professor, UCLA Hematology & Oncology, Associate Director of Drug Development and Director of Clinical Trials in Thoracic Oncology. ‘Rociletinib has shown very encouraging and durable activity in the most advanced mutant EGFR lung cancer patients, including in a large population of patients with CNS metastases. Importantly, the data continue to show activity in both T790M-positive and T790M-negative patients, which gives us a potential treatment option for all patients who have progressed on their initial EGFR targeted therapy.’ “


Pfizer Drug Shows Early Promise in Xalkori-Resistant Lung Cancer-Study

“An experimental Pfizer Inc drug that aims to help lung cancer patients with specific genetic mutations who have stopped responding to the company’s Xalkori was showing promise in a small, early stage study, according to preliminary data revealed on Wednesday.

“The ongoing Phase I trial of the drug, PF-3922, was designed to determine if there is a maximum tolerable dose and which dose or doses to test in future larger trials.

“But researchers found some early evidence of efficacy, according to a brief summary of the study that will be presented at the upcoming American Society of Clinical Oncology (ASCO)meeting in Chicago later this month.

“Of 15 patients evaluated for efficacy, six, or 40 percent, had partial responses, meaning tumor shrinkage of at least 30 percent. Intracranial responses were observed in five patients, indicating that the drug had successfully crossed the blood/brain barrier to attack tumors in the brain, which are common in advanced, or metastatic, lung cancer.

” ‘There’s encouraging clinical activity despite that it’s an early study,’ said Ronit Simantov, head of medical affairs for Pfizer oncology.”