Two Mutations Linked to Success of Adoptive T-Cell Therapy in Melanoma

“Two novel mutations, KIF2C and POLA2, appeared to be linked to complete cancer regression in two patients with metastatic melanoma who underwent adoptive T-cell immunotherapy, according to study results.

“ ‘This study provides the technical solution to identify mutated tumor targets that can stimulate immune responses, which is one of the major bottlenecks in developing a new generation of adoptive T-cell therapy,’ Steven A. Rosenberg, MD, PhD, chief of surgery at the NCI, said in a press release. ‘The two targets identified in this study play important roles in cancer cell proliferation.’ ”

Editor’s note: In order to improve new treatments so that more people can benefit from them, it is useful to figure out why they are particularly successful for certain patients. In this story, researchers wished to know why two people with metastatic melanoma experienced complete disappearance of their tumors in response to a treatment called adoptive T-cell transfer. In adoptive T cell transfer, immune system cells are collected from either the patient’s tumor or the blood supply near the tumor. In the laboratory, these cells are multiplied to produce high numbers of ‘killer’ T cells, which are then infused back into the patient, where they are able to recognize and attack cancer cells. It was found that the two patients with exceptionally good responses had two genetic mutations in their tumor cells that the T cells were able to attack directly. The discovery could help researchers learn how to make adoptive T cell transfer more effective for more people.


ASCO 2014 Lung Cancer Roundup


Every year, thousands of people gather in Chicago, Illinois, for the American Society of Clinical Oncology (ASCO) Annual Meeting. The largest meeting of its kind, ASCO brings together doctors, researchers, nurses, patient advocates, pharmaceutical company representatives, and more to discuss the latest in cancer research. Here are some of the most exciting new developments in lung cancer research presented last week at ASCO 2014: Continue reading…


Melanoma of the Eye: Better Diagnostics and Future Treatments


Laitr Keiows / Wikimedia Commons Laitr Keiows / Wikimedia Commons

Ocular melanomas, or melanomas found in the eye, are fairly infrequent, but they are the most common type of eye tumor. In the U.S., there are about 2,000 cases diagnosed each year. They occur within one of the three parts of the eye: the iris, the choroid, or the ciliary body. Collectively, these are known as the ‘uvea,’ hence an alternative name for this cancer: uveal melanoma. Continue reading…


Researchers Develop Process to Help Personalize Treatment for Lung Cancer Patients

“Moffitt Cancer Center researchers, in collaboration with the Lung Cancer Mutation Consortium, have developed a process to analyze mutated genes in lung adenocarcinoma to help better select personalized treatment options for patients. Adenocarcinoma is the most common type of lung cancer in the United States with approximately 130,000 people diagnosed each year.

“The study, published in the May 21 issue of The Journal of the American Medical Association, investigated 10 highly mutated and altered genes that contribute to cancer progression, termed oncogenic driver genes, in more than 1,000 lung cancer patients. Patients with adenocarcinoma have a high probability of having mutated oncogenic driver genes in their tumors.”

Editor’s note: More and more, doctors are prescribing personalized cancer treatments based on genetic mutations found in patients’ tumors. Learn more about personalized medicine for lung cancer in The Basics.


Prevalence of New Genetic Driver in Lung Cancer Shown in Study

“A line has been drawn from mutation of the gene NTRK1, to its role as an oncogene in non-small cell lung cancer, to treatment that targets this mutation. ‘Everything we know about lung cancer points to the idea that when we find one of these genetic drivers and can target it with a drug, patients will respond and tend to have a good amount of time on drug before it becomes ineffective. Obviously we can’t guarantee the effectiveness of targeting the NTRK1 mutation at this point, but everything we know about these kinds of genes makes us extremely hopeful,’ says one researcher.”

Editor’s note: A new targeted therapy treatment may be on the horizon for some lung cancer patients. Targeted therapies work by targeting specific molecules inside cancer cells. Often, these molecules are proteins that are mutated and cause cancer cells to multiply rapidly, contributing to tumor growth. There are several mutated proteins commonly found in non-small cell lung cancer (NSCLC) tumors. For a given patient, these can be detected by molecular testing, and based on the results, doctors can prescribe certain targeted therapy drugs. A newly discovered mutation called NTRK1 is being explored as a potential target for a new targeted therapy. To test the new drug, called LOXO-101, scientists have started a new clinical trial and are enrolling patients whose tumors have NTRK1 mutations.


Responses with Crizotinib in MET-Amplified Lung Cancer Show New Targetable Form of Disease

In 2011, the drug crizotinib earned accelerated approval by the US FDA to target the subset of advanced non-small cell lung cancers caused by rearrangements of the anaplastic lymphoma kinase (ALK) gene, and subsequently was granted regular approval in 2013. The drug also has shown dramatic responses in patients whose lung cancers harbored a different molecular abnormality, namely ROS1 gene rearrangements. Previously unreported phase 1 clinical trial results now show that crizotinib may have a third important molecular target. In advanced non-small cell lung cancer patients with intermediate and high amplifications of the MET gene, crizotinib produced either disease stabilization or tumor response. Sixty-seven percent of patients with high MET amplification showed prolonged response to the drug, which lasted from approximately 6 months to nearly 2.5 years.”

Editor’s note: Crizotinib (aka Xalkori) is a targeted therapy drug that kills cancer cells by targeting certain molecules found in the cells. It was already known that crizotinib works well for some patients with advanced non-small cell lung cancer (NSCLC) whose cancer cells have mutations in the ALK gene and in the ROS1 gene; such mutations, or “molecular biomarkers,” are detected by a medical procedure known as “molecular testing,” or “genetic testing.” Now, scientists say that crizotinib may also be effective for patients with advanced NSCLC whose tumors have abnormally high activity of a protein called MET, which can also be detected via molecular testing.


US ‘Proof-of-Concept’ Trial Confirms Promise of Stratified Lung Cancer Treatment

“Routine tests that look for multiple, specific genetic changes in patients’ lung tumours could help doctors select targeted treatments, a US study has confirmed.

“The research, published in the Journal of the American Medical Association, looked simultaneously for ten specific cancer-driving genetic changes in the tumours of 733 patients with adenocarcinoma, the most common type of lung cancer.”

Editor’s note: Learn more about genetic testing and personalized approaches to lung cancer treatment in our Lung Cancer KnowledgeBase.


Thwarting Drug Resistance in Lung Cancer


If you’ve read up on lung cancer research in the last few years, you probably know that large strides have been made in targeted therapies for non-small cell lung cancer (NSCLC). Targeted therapies are drugs that identify and attack specific mutated proteins that are detected in tumors. Because noncancerous cells do not have these specific mutations, targeted therapies can make a beeline for cancer, while leaving healthy tissue unharmed. Continue reading…


New EGFR Inhibitor AZD9291 Shows Promising Activity in Treatment-Resistant Non–Small Cell Lung Cancer

“Findings from a phase I study of a new mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, AZD9291, point to a promising new treatment option for patients with advanced, EGFR-mutant, non–small cell lung cancer (NSCLC) that is resistant to standard EGFR inhibitors. Roughly 50% of patients experienced tumor shrinkage, and the drug worked particularly well in patients with the T790M mutation (detected in 60% of patients), which causes the most common form of EGFR therapy resistance. The study was presented at a presscast in advance of the 2014 ASCO Annual Meeting (Abstract 8009^).”

Editor’s note: This story is about a new targeted therapy drug called AZD9291 that is designed to attack tumors with a mutation in the EGFR gene, as detected by molecular testing. In particular, it is designed for patients who are resistant to other so-called EGFR inhibitors as a result of developing a particular EGFR mutation known as T790M. In a clinical trial to test the drug in patients, it was found to show promising results for patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations, and even better results in patients with the T790M mutation.