Potential new drug for lung cancer

 

Potential new drug target for lung cancer

Scientists zero in on how lung cancer spreads

 

This image shows normal cells (left) compared to when the cell ties are broken down (right). Scientists have taken microscopic images revealing that the protein ties tethering cells together are severed in lung cancer cells -- meaning they can break loose and spread, according to research published in Cell Reports December 24. The researchers at the Cancer Research UK Manchester Institute discovered that the ties which lash cells together -- controlled by a protein called TIAM1 -- are chopped up when cell maintenance work goes wrong. Healthy cells routinely scrap old cell parts so they can be broken down and used again. But this process spirals out of control in lung cancer cells, which scrap too many TIAM1 ties**. Targeting this recycling process could stop lung cancer from spreading by keeping the cells stuck firmly together. Lead researcher, Dr Angeliki Malliri, at the Cancer Research UK Manchester Institute at the University of Manchester, said: "This important research shows for the first time how lung cancer cells sever ties with their neighbours and start to spread around the body, by hijacking the cells' recycling process and sending it into overdrive. Targeting this flaw could help stop lung cancer from spreading." There are almost 43,500 new cases of lung cancer in the UK each year. It is the most common cause of cancer deaths and kills more than 35,000 people in the UK each year. Nell Barrie, Cancer Research UK's senior science information manager, said: "Lung cancer causes more than one in five of all cancer deaths in the UK and it's vital that we find effective new treatments to fight the disease and save more lives. "Early-stage research like this is essential to find treatments which could one day block cancer spread -- which would be a game changer. It's also crucial that we find ways to diagnose the disease earlier, when treatment is more likely to be successful and the cancer is less likely to have spread." The University of Manchester, including the Cancer Research UK Manchester Institute, joined forces with Cancer Research UK and The Christie NHS Foundation Trust to form the Manchester Cancer Research Centre, allowing doctors and scientists to work closely together to turn scientific advances into patient benefits sooner. Story Source: The above story is based on materials provided by Cancer Research UK. Note: Materials may be edited for content and length. Journal Reference: Lynsey Vaughan, Chong-Teik Tan, Anna Chapman, Daisuke Nonaka, Natalie A. Mack, Duncan Smith, Richard Booton, Adam F.L. Hurlstone, Angeliki Malliri. HUWE1 Ubiquitylates and Degrades the RAC Activator TIAM1 Promoting Cell-Cell Adhesion Disassembly, Migration, and Invasion. Cell Reports, 2014; DOI: 10.1016/j.celrep.2014.12.012

Technology developed to improve lung cancer detection, treatment

 

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Researchers from Loyola University Chicago Stritch School of Medicine have developed a technology that improves the detection of tumors during radiation therapy for early-stage lung cancer.

John Roeske, PhD, and colleagues presented how they developed and evaluated the technology at the recent annual meeting of the American Society for Therapeutic Radiology and Oncology.

Their approach uses dual-energy imaging combined with fluoroscopy to view tumors during radiation therapy. This technology does not require an X-ray that produces both high-and low-energy images. Existing hardware can be used to eliminate visuals of the ribs and other bones making it easier to see the tumor.

"Dual-energy imaging has been used for decades by radiologists to detect lung tumors," said Roeske, professor and director of Radiation Physics, Department of Radiation Oncology. "When combined with fluoroscopy, the hybrid dual-energy technology can enhance the visibility of tumors to improve treatment for patients."

Roeske and his colleagues have a patent on the technology. They report that if it becomes commercially available, their approach would provide a cost-benefit to hospitals.

"This technology does not require that hospitals replace their standard X-ray machines since the dual-energy images are created using a software approach," Roeske said. "The hybrid technique removes present obstacles making this a great benefit to clinicians and patients."

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Story Source:

The above story is based on materials provided by Loyola University Health System. Note: Materials may be edited for content and length.

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Prognostic factors identified for peripheral squamous cell carcinomas of the lung

 

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A better survival outcome is associated with low blood levels of squamous cell carcinoma antigen, or absence of tumor invasion either into the space between the lungs and chest wall or into blood vessels of individuals with a peripheral squamous cell carcinoma, a type of non-small cell lung cancer (NSCLC).

Lung cancer is the most common cause of cancer-related death worldwide and lung squamous cell carcinomas (SCC) account for 20-30% of all NSCLC. SCC can be classified as either central (c-SCC) or peripheral (p-SCC) depending on the primary location. While c-SCC is the most prevalent, the incidence of p-SCC is increasing and the clinical and biological behaviors of p-SCC remain unclear.

Researchers from Keio University School of Medicine and Saiseikai Utsunomiya Hospital in Japan evaluated several clinical and pathological variables in 280 patients with surgically removed p-SCC in order to identify potential prognostic factors.

Results published in the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC), show that low preoperative levels of squamous cell carcinoma antigen in the serum or either absence of tumor invasion into the pleura (the space between the lungs and chest wall) or tumor vasculature are independent prognostic factors for patients with any stage of p-SCC. These patients had an extended period without disease recurrence and longer overall survival. The same was also seen for the sub-group of patients with early stage I disease.

The authors note that "our study revealed that p-SCCs with pleural or vascular invasion or high serum SCC antigen are more likely to recur than those without it; even in stage I patients. Pleural and/or vascular invasion are thought to be essential steps in the progression and metastasis of p-SCCs and high serum SCC antigen may suggest micro-metastases at the time of surgery." The authors propose that "patients with high serum SCC levels, vascular invasion or pleural invasion should have their tumor stage upgraded in order to reflect the clear differences in survival. Clinical trials should be performed to evaluate if postoperative chemotherapy would benefit these patients who typically may not receive chemotherapy because of their early stage."

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Story Source:

The above story is based on materials provided by International Association for the Study of Lung Cancer. The original article was written by Murry W. Wynes, Ph.D.. Note: Materials may be edited for content and length.

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Journal Reference:

1. Tomonari Kinoshita, Takashi Ohtsuka, Tai Hato, Taichiro Goto, Ikuo Kamiyama, Atsushi Tajima, Katsura Emoto, Yuichiro Hayashi, Mitsutomo Kohno. Prognostic Factors Based on Clinicopathological Data Among the Patients with Resected Peripheral Squamous Cell Carcinomas of the Lung. Journal of Thoracic Oncology, 2014; 1 DOI: 10.1097/JTO.0000000000000338

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Anaplastic lymphoma kinase immunohistochemistry testing comparable to fluorescence [in situ] hybridization testing

 

October 23, 2014

International Association for the Study of Lung Cancer

Sixteen institutions across Europe collaborated together to show for the first time that a semi-quantitative anaplastic lymphoma kinase protein expression test, immunohistochemistry, is reliable amongst several laboratories and reviewers when test methodology and result interpretation are strictly standardized and the scoring pathologists are appropriately trained on the test.

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Sixteen institutions across Europe collaborated together to show for the first time that a semi-quantitative anaplastic lymphoma kinase (ALK) protein expression test, immunohistochemistry (IHC), is reliable amongst several laboratories and reviewers when test methodology and result interpretation are strictly standardized and the scoring pathologists are appropriately trained on the test.

ALK tyrosine kinase inhibitors (TKIs) shrink tumors and increase progression-free survival in late-stage non-small cell lung cancer (NSCLC) patients positive for ALK as determined by the fluorescence in situ hybridization (FISH) test, a test for DNA rearrangement within the gene. Testing positive for ALK is required in order to be prescribed the therapeutic inhibitors. However, the FISH test is expensive, time-consuming, and requires specialized equipment and expertise. Many other studies have shown comparable results between IHC and FISH but none have compared a highly standardized test and scoring methodology performed at multiple institutions in numerous countries.

Fifteen well-characterized NSCLC specimens were tested and scored for IHC at 16 institutes of pathology in Belgium, Denmark, France, Germany, Scotland, Spain, Sweden and Switzerland. The specimens were pre-tested 3 times by FISH at 2 separate institutions in Germany. Prior to the IHC testing all the equipment was standardized between all the institutions and the scoring pathologists all attended an internet-based training session with teaching cases.

The results published in the November issue of the Journal of Thoracic Oncology, the official journal for the International Association for the Study of Lung Cancer (IASLC), show that all 16 institutions agreed with 100% concordance on the 7 FISH/IHC negative and on 4 FISH/IHC positive specimens. There was also 100% concordance from all institutions on 2 obvious IHC positive cases that were uncertain by FISH ("borderline"). These 2 cases were confirmed ALK positive by a third test, reverse transcription-polymerase chain reaction (RT-PCR). The last 2 cases were ALK-FISH positive and were scored IHC positive by 15/16 and 12/16 institutions, respectively. However, those not scoring these 2 cases as unequivocal ALK IHC positive, called them IHC equivocal and would have demanded an additional ALK test (FISH, PCR) under diagnostic conditions.

The authors conclude "after harmonization of the staining instruments and training of the observers, the ALK IHC assay can be regarded as a reliable multicenter technique for the detection of ALK protein expression." For the future the authors note "there is need to compare validated ALK IHC assays and ALK-FISH in clinical trials as therapy response data of patients with differing ALK IHC and FISH results will help to implement ALK-IHC not only as a prescreening tool, but also as a potential stand-alone test (at least in cases displaying a clear staining pattern). Until then ALK diagnosis should be based on the rational application of both methods adapted to the given case as FISH has some disadvantages and even validated IHC may produce equivocal staining patterns."

Lead author Dr. Maximilian von Laffert, senior author Dr. Manfred Dietel, and co-authors Drs. Arne Warth, Keith M. Kerr, Fernando Lopez-Rios, Patrick Pauwels, Lukas Bubendorf, and Alex Soltermann are members of IASLC.

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Story Source:

The above story is based on materials provided by International Association for the Study of Lung Cancer. The original article was written by Murry W. Wynes. Note: Materials may be edited for content and length.

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Journal Reference:

1. Maximilian von Laffert, Arne Warth, Roland Penzel, Peter Schirmacher, Keith M. Kerr, Göran Elmberger, Hans-Ulrich Schildhaus, Reinhard Büttner, Fernando Lopez-Rios, Simone Reu, Thomas Kirchner, Patrick Pauwels, Katja Specht, Enken Drecoll, Heinz Höfler, Daniela Aust, Gustavo Baretton, Lukas Bubendorf, Sonja Stallmann, Annette Fisseler-Eckhoff, Alex Soltermann, Verena Tischler, Holger Moch, Frederique Penault-Llorca, Hendrik Hager, Frank Schäper, Dido Lenze, Michael Hummel, Manfred Dietel. Multicenter Immunohistochemical ALK-Testing of Non–Small-Cell Lung Cancer Shows High Concordance after Harmonization of Techniques and Interpretation Criteria. Journal of Thoracic Oncology, 2014; 9 (11): 1685 DOI: 10.1097/JTO.0000000000000332

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Novel software application can stratify early-stage non-small cell lung cancer patients

 

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Computer-Aided Nodule Assessment and Risk Yield, is a novel software tool developed at Mayo Clinic that can automatically quantitate adenocarcinoma pulmonary nodule characteristics from non-invasive high resolution computed tomography (HRCT) images and stratify non-small cell lung cancer (NSCLC) patients into risk groups that have significantly different disease-free survival outcomes.

The majority of NSCLC patients are diagnosed with advanced-stage disease which is concomitant with an exceptionally poor prognosis, 5-year survival rate of 4%. In contrast, tumors detected at an early stage have 5-year survival rates of 54%. The National Lung Cancer Screening Trial (NLST) demonstrated a 20% reduction in lung-cancer specific mortality by screening with HRCT, but many detected nodules are non-cancerous and slow-growing, which can lead to costly and risky overdiagnosis and overtreatment. Thus, better risk classification based on the nodules characteristics is desirable.

HRCT images from 264 clinical stage I pulmonary nodules of the lung adenocarcinoma spectrum were analyzed with the CANARY system and the software used an unsupervised clustering algorithm to classify the patients into categories of similar nodule characteristics.

The results published in the November issue of the Journal of Thoracic Oncology, the official journal for the International Association for the Study of Lung Cancer (IASLC), show that the adenocarcinomas naturally segregated into 3 groups based on HRCT characteristics. The three identified groups corresponded to good, intermediate, and poor postoperative outcomes with 5-year disease-free survival rates of 100%, 73% and 51%, respectively.

"Our preliminary assessment suggests CANARY represents a robust risk stratification tool that can be utilized with a wide variety of HRCT techniques and equipment for retrospective or prospective evaluation of lung nodules in a real-world setting," conclude the authors. Dr. Raghunath, lead author of the study, suggests "HRCT-based CANARY classification could ultimately guide the individualized treatment of HRCT-detected lesions with nodules noninvasively categorized as "good" managed with less aggressive surgical approaches, noninvasive or minimally invasive therapy or watchful waiting, whereas nodules that have characteristics corresponding to the "poor" group would be managed with current standard of care, such as lobectomy, and perhaps additional adjuvant therapy."

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Story Source:

The above story is based on materials provided by International Association for the Study of Lung Cancer. The original article was written by Murry W. Wynes. Note: Materials may be edited for content and length.

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Journal Reference:

1. Sushravya Raghunath, Fabien Maldonado, Srinivasan Rajagopalan, Ronald A. Karwoski, Zackary S. DePew, Brian J. Bartholmai, Tobias Peikert, Richard A. Robb. Noninvasive Risk Stratification of Lung Adenocarcinoma using Quantitative Computed Tomography. Journal of Thoracic Oncology, 2014; 9 (11): 1698 DOI: 10.1097/JTO.0000000000000319

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Customizing chemotherapy in lung cancer: New phase II data reported

 

September 27, 2014

European Society for Medical Oncology (ESMO)

Measuring the expression levels of an enzyme involved in DNA synthesis can help predict the response of lung cancers to certain treatments, a Korean study has shown. In a randomized phase II study, researchers showed that patients whose lung cancers expressed low levels of an enzyme called thymidylate synthase experienced a greater benefit from treatment with the combination of pemetrexed and cisplatin than those whose tumors expressed high levels.

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Measuring the expression levels of an enzyme involved in DNA synthesis can help predict the response of lung cancers to certain treatments, a Korean study has shown at the ESMO 2014 Congress in Madrid.

In a randomized phase II study, researchers showed that patients whose lung cancers expressed low levels of an enzyme called thymidylate synthase experienced a greater benefit from treatment with the combination of pemetrexed and cisplatin than those whose tumours expressed high levels.

"Thymidylate synthase is one of the proteins that is targeted by pemetrexed which is the most widely used chemotherapeutic regimen in the treatment of non-squamous NSCLC," explains study author Professor Myung-Ju Ahn, from the Section of Hematology-Oncology at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

"In this study, we tried to evaluate whether expression of thymidylate synthase is a predictive factor for response to pemetrexed plus cisplatin chemotherapy compared with gemcitabine plus cisplatin in non-squamous cell lung cancer patients."

In terms of response rate and progression-free survival, the clinical benefits of the pemetrexed combination compared to other regimen were more prominent in those patients who expressed low levels of the molecule, Ahn said.

"This suggests that thymidylate synthase can be used as a predictive biomarker. Furthermore, we also found that low thymidylate synthase expression was associated with prolonged overall survival irrespective of which chemotherapeutic regimen the patients received, suggesting that its expression can also serve as a prognostic biomarker."

In the study, patients with more than 10% of tumour cells expressing thymidylate synthase were grouped as 'TS-positive' and those with 10% or less were grouped as a 'TS-negative'. Among 315 patients, the response rate of pemetrexed and gemcitabine were 47.0% and 21.1% in TS- patients, and 40.3% and 39.2% in the TS+ group. The median progression-free survival of pemetrexed and gemcitabine combinations were 6.4 and 5.5 months in the TS- group and 5.9 and 5.3 months in the TS+ group.

The median overall survival in response to treatment with the pemetrexed combination and the gemcitabine combination were not different in the TS- group or in the TS+ group, however those with TS-negative tumours tended to survive for longer.

The take-home message is that thymidylate synthase could be a useful biomarker in this setting, Ahn says.

"In non-squamous cell NSCLC, thymidylate synthase-negative patients get more clinical benefit from pemetrexed/cisplatin combination therapy. Furthermore, multivariate analysis of the present study showed that TS negative expression was significantly associated with longer survival, along with younger age and EGFR mutation, suggesting it is a good independent prognostic marker."

"This study opens the gates for thymidylate synthase (TS)-customized chemotherapy in advanced NSCLC," commented Dr Rafael Rosell, director of the Cancer Biology and Precision Medicine Program at the Catalan Institute of Oncology, Spain.

"They focus their research on patients with non-squamous NSCLC and show that low-TS expressing patients have a significantly better response and outcome, either with pemetrexed or gemcitabine, in combination with cisplatin."

"Over-expression of TS could behave as an oncogene and therefore TS could be not only a predictive marker of response to antimetabolite drugs, but also a prognostic marker," Rosell said. "Therefore, it could be of interest to see what the relevance of using TS as an overall biomarker could be for predicting chemotherapy outcome. It would be of great interest to gain further insights on the mechanisms of TS up-regulation since a master oncogene, astrocyte elevated gene-1 (AEG-1) has been shown to induce the transcription factor LSF (late SV40 factor) that directly up-regulates TS." (Cancer Res 2009; 69:8529).

Scan may identify lung cancer patients who will benefit from folate-targeted drug A non-invasive method for measuring the expression folate receptors on tumour cells can identify which patients with advanced lung cancer are likely to derive greater benefit from combination chemotherapy with the investigational drug vintafolide, researchers report at ESMO 2014.

At the meeting, medical oncologist Dr Rohit Lal from Guy's & St Thomas' NHS Foundation Trust in London, reported results from the phase II TARGET trial, which included 199 patients with non-small cell lung cancer who had already been treated with other drugs, and whose tumours all expressed the folate receptor.

Folic acid and folates are key to the synthesis of DNA and RNA, and abnormalities in folate pathways and folate receptors are involved in many cancers including lung cancer, Lal explains. Vintafolide is a drug targeted to the folate receptor, and is being developed together with an imaging agent that enables non-invasive imaging of folate receptor expression in tumours.

"Our results show a statistical improvement in overall survival and a promising progression-free survival signal with vintafolide and docetaxel for advanced lung adenocarcinoma patients selected by an imaging biomarker for the folate receptor. These patients also had a higher rate of radiological disease control. More patients treated in the vintafolide combination arm required dose adjustment. The results warrant confirmation in a phase III study," Lal said.

"In this phase II trial, adenocarcinoma patients treated with the vintafolide combination were half as likely to have succumbed from their disease than patients in the docetaxel group. These results will need to be validated in a phase III trial," Lal said.

"Choosing treatments based on tumour biopsy tests is well established. The TARGET trial results show a positive outcome for 2nd-line advanced lung adenocarcinoma patients and may show that by using a scan we can select advanced stage lung cancer patients that may derive a greater benefit from combination chemotherapy."

"This group reports the results of a revolutionary study employing a non-invasive method to detect folate receptor expression in NSCLC cells and the relation to treatment with vintafolide, targeting the folate receptor," Rosell noted. "The preliminary results are promising, indicating that the combination of vintafolide and docetaxel could be effective in advanced lung adenocarcinoma patients selected by imaging tracer for the folate receptor."

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Story Source:

The above story is based on materials provided by European Society for Medical Oncology (ESMO). Note: Materials may be edited for content and length.

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Crizotinib treatment effective against ROS1-positive lung cancer, study suggests

 

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Treatment with the targeted therapy drug crizotinib effectively halts the growth of lung tumors driven by rearrangements of the ROS1 gene. In an article receiving Online First publication in the New England Journal of Medicine to coincide with a presentation at the European Society for Medical Oncology meeting, an international research team reports that crizotinib treatment led to significant tumor shrinkage in 36 of 50 study participants and suppressed tumor growth in another 9.

"Prior to this study, there were a handful of reports describing marked responses to crizotinib in individual patients with ROS1-positive lung tumors," says Alice Shaw, MD, PhD, of the Massachusetts General Hospital (MGH) Cancer Center, lead author of the NEJM report. "This is the first definitive study to establish crizotinib's activity in a large group of patients with ROS1-positive lung cancer and to confirm that ROS1 is a bona fide therapeutic target in those patients."

Crizotinib currently is FDA-approved to treat non-small-cell lung cancers (NSCLC) driven by rearrangments in the ALK gene, which make up around 4 percent of cases. An MGH Cancer Center report published in 2012 reported that 1 to 2 percent of NSCLCs are driven by rearrangements in ROS1, which encodes a protein with significant structural similarities to that encoded by the ALK gene.

The current study, an expansion of the original phase 1 crizotinib trial, enrolled 50 patients with ROS1-positive NSCLC, beginning in late 2010. Patients received twice daily doses of crizotinib. As noted above, tumor size was significantly reduced in 72 percent of patients and tumor growth was halted in an additional 18 percent. The average duration of response was over 17 months. At the end of the study, 25 of the 50 patients were still receiving crizotinib with no evidence of tumor progression.

As with other targeted cancer therapy drugs, treatment resistance developed in a number of participants, but the effectiveness of crizotinib appeared to last longer in ROS1-positive patients than in patients with ALK-positive tumors. "Almost all patients treated with targeted therapies eventually develop resistance," explains Shaw, an associate professor of Medicine at Harvard Medical School (HMS). "Fortunately, the remissions induced by crizotinib in ROS1-positive patients are quite prolonged, and resistance appears to emerge much later, on average, than what we have seen with other targeted therapies for lung cancer and melanoma."

The authors note that development of efficient laboratory diagnostics has been critical to identification of ROS1 rearrangements and of other genetic alterations that drive tumor growth. John Iafrate, MD, PhD, medical director of the MGH Center for Integrated Diagnostics and associate professor of Pathology at HMS, who is senior author of the study comments, "This is a great example of success in personalized medicine. While NSCLC patients with ROS1 fusions are rare, if you devote the diagnostic laboratory resources to find that 1 to 2 percent of patients, you will make a real difference."

While crizotinib's FDA approval currently covers only ALK-positive NSCLC, Shaw notes that National Comprehensive Cancer Network guidelines recommend that patients with advanced lung cancer be considered for ROS1 testing and that crizotinib should be used to treat ROS1-positive patients.

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Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.

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Prevalence of new genetic driver in lung cancer shown in study

 

May 31, 2014

University of Colorado Cancer Center

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.

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A University of Colorado Cancer Center study presented at the 50th Annual Meeting of the American Society for Clinical Oncology (ASCO) draws a line from mutation of the gene NTRK1, to its role as an oncogene in non-small cell lung cancer, to treatment that targets this mutation. The current study reports the prevalence of the NTRK1 mutation in an unselected population of 450 lung cancer samples, with >1% percent of patients testing positive. This and other work from Dr. Doebele's group forms the basis of a phase 1 clinical trial targeting NTRK1 mutations in advanced solid tumors (NCT02122913).

"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 Robert C. Doebele, MD, PhD, investigator at the CU Cancer Center and associate professor of Medical Oncology at the CU School of Medicine.

Previous work in collaboration with Pasi A. Jänne, MD, PhD from the Dana-Farber Cancer Institute, examined lung cancer tumor samples from 36 "pan-negative" patients, meaning that no other driver oncogene had been identified. Next-gen sequencing at Foundation Medicine (Cambridge, MA) identified NTRK1 gene fusions as the potential driver in two of these samples.

Doebele and colleagues took the finding back to CU labs, where Marileila Varella-Garcia, PhD, developed a specific test for NTRK1 fusions based on fluorescence in situ hybridization (FISH), similar to what is currently used for ALK, ROS1 and RET fusions. This test would allow rapid detection of NRTK1 oncogenes in patient samples. "But no one had ever looked for NTRK1 mutations in a large series of unbiased patient samples," Doebele says. "The point of this study was to get a better sense of how many lung cancer patients are likely to be positive for NTRK1 mutations and what these patients are likely to look like."

Of 450 evaluated patient samples of non-small cell lung cancer, 5 tested "positive" and another 12 are considered suspicious for the mutation. Next generation sequencing studies revealed 5 previously undescribed NTRK1 mutations. Ongoing work seeks to tease apart the subtleties of diagnosis to further refine the criteria used to decide which tumors are truly created by the NTRK1 mutation.

Again, just as the FDA-approved drug crizotinib targets ALK fusions in an affected subset of lung cancer, the goal of the current line of research is to identify patients whose cancers are caused by NTRK1 and similarly target these patients with a drug that silences the problem gene. Toward that goal, Array BioPharma (Boulder, CO) provided candidate drugs to inhibit mutated NTRK1. Loxo Oncology, Inc. has managed further testing of the leading drug candidate, now known as LOXO-101. A phase 1a/1b clinical trial of the drug in advanced solid tumors is now recruiting patients.

"We found the mutation in a patient sample in 2012, published a manuscript in 2013 describing NTRK1 as a driver of lung cancer, and now here we are in May 2014 laying the groundwork for a clinical trial of drugs targeting this mutation," Doebele says. "Having seen this approach work well with other mutations in the past, the team is optimistic that this research could help control another important subset of lung cancers."

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Story Source:

The above story is based on materials provided by University of Colorado Cancer Center. The original article was written by Garth Sundem. Note: Materials may be edited for content and length.