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New Targeted Drugs May Offer Treatment for KRAS-Mutant Lung Cancer

New Targeted Drugs May Offer Treatment for KRAS-Mutant Lung Cancer | Lung Cancer Dispatch | Scoop.it

Abnormalities in the KRAS gene are the most common mutations in lung cancer, especially in lung adenocarcinoma, a type of non-small cell lung cancer (NSCLC). However, no effective targeted therapy directed at KRAS has been found. Instead, researchers have begun to focus on blocking molecules 'downstream' in the chain of chemical reactions through which KRAS affects the cell. Two such molecules are TBK1 and MEK. A recent study found that the drug CYT387 blocks TBK1. CYT387 reduced tumor growth in mice with KRAS-mutant lung adenocarcinoma. Also in mice, CYT387 and the MEK inhibitor AZD6244, given together, shrank aggressive lung tumors with mutations in both the KRAS and the TP53 gene. Researchers now hope to investigate the two drugs in people.

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ASCO Post  |  Jan 29, 2014

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Lung Cancer Drug BGB324 May Counteract Drug Resistance

Lung Cancer Drug BGB324 May Counteract Drug Resistance | Lung Cancer Dispatch | Scoop.it

The protein Axl has been associated with cell transformation processes that contribute to the spread of cancer through the body and to cancers becoming drug resistant. A recent study investigated the effect of the Axl inhibitor BGB324 on non-small cell lung cancer (NSCLC) cells that had become resistant to EGFR inhibitors like erlotinib (Tarceva). BGB324 restored the effectiveness of EGFR inhibitors against these cancer cells, which had been grown either in a matrix or as tumors in mice. BGB324 also appeared to enhance the effectiveness of the chemotherapy drug docetaxel (Taxotere) and of bevacizumab (Avastin). BGB324 may therefore be a promising new candidate for treating drug-resistant NSCLC. The drug will be tested in a phase Ib clinical trial for NSCLC in 2014.

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Medical News Today  |  Jan 13, 2014

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Attacking Lung Cancer Cells by Blocking Antioxidants

Attacking Lung Cancer Cells by Blocking Antioxidants | Lung Cancer Dispatch | Scoop.it

As a byproduct of their rapid metabolism and growth, cancer cells frequently produce high levels of so-called free radicals–highly reactive particles that can damage cells. To protect themselves, cancer cells also produce antioxidants, which deactivate the free radicals. Drugs that block these antioxidants should therefore selectively impair cancer cells, while having relatively little effect on healthy cells that do not experience high levels of free radicals. Researchers found that the antioxidant-inhibiting drug ATN-224 induced the death of non-small lung cancer (NSCLC) cells in cell culture. ATN-224 also decreased the number and size of lung tumors in mice injected with NSCLC cells.

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Medical Xpress  |  Dec 2, 2013

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New Compound Targets Previously 'Undruggable' Cancer-Driving Mutation in KRAS Gene

New Compound Targets Previously 'Undruggable' Cancer-Driving Mutation in KRAS Gene | Lung Cancer Dispatch | Scoop.it

Mutations in the KRAS gene are the most common cancer-driving mutations in all cancers; they occur in 20% of lung cancers and 40% of colon cancers. KRAS-mutant cancers are aggressive and do not respond well to current treatments. Although the importance of KRAS mutations in cancer has been known for over 30 years, scientists have so far not succeeded in developing a drug targeting them. Now researchers have located a previously undetected 'pocket' on a certain mutated form of the KRAS protein. The mutation, called KRAS(G12C), occurs in 7% of lung cancer and 9% of colorectal cancer patients. The researchers then created molecules that bind to the 'pocket' and inhibit the mutant KRAS, but not normal KRAS protein. They hope to develop these compounds into drugs against KRAS-mutant cancers.

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Medical Xpress  |  Nov 20, 2013

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New Biomarker May Allow Development of Less Invasive Test for Lung Cancer, New Lung Cancer Treatments

New Biomarker May Allow Development of Less Invasive Test for Lung Cancer, New Lung Cancer Treatments | Lung Cancer Dispatch | Scoop.it

MicroRNAs are small molecules that turn down or switch off other genes and influence a wide range of processes in cells throughout the body. Researchers discovered that the microRNA 4423 (miR-4423) is found in higher levels in cells lining the airways of the lungs than in other parts of the body. But, levels of miR-4423 are lower in lung tumors and in otherwise normal-appearing airway cells of people with lung cancer. Because miR-4423 is found on the surface of the airways, measuring miR-4423 levels may serve as a relatively noninvasive test for lung cancer. Adding miR-4423 back inhibited the growth of lung cancer cells in cell cultures and decreased the size of lung cancer tumors implanted into mice. Increasing miR-4423 levels may therefore also form the basis of future lung cancer treatments.

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ScienceDaily | Oct 25, 2013

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New Drug May Offer Option for Lung Cancer Patients Resistant to Tarceva/Iressa

New Drug May Offer Option for Lung Cancer Patients Resistant to Tarceva/Iressa | Lung Cancer Dispatch | Scoop.it

Drugs known as EGFR inhibitors—like erlotinib (Tarceva) and gefitinib (Iressa)—are used to treat non-small cell lung cancer (NSCLC) with so-called 'activating mutations' in the EGFR gene. Unfortunately, drug resistance develops relatively quickly in most patients. Resistance is often due to additional EGFR mutations, so-called 'resistance mutations,' such as EGFR T790M. Researcher have developed a new EGFR inhibitor, AZD9291, which targets both activating and resistance mutant forms of EGFR. AZD9291 inhibited the growth of EGFR-mutant NSCLC cell cultures and eradicated lung cancer tumors with either activating or resistance mutations in mice. Because AZD9291 is less active against normal, non-mutant EGFR, it may have fewer side effects than other EGFR inhibitors. Initial tests of AZD9291 in patients have been promising.

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ScienceDaily | Oct 20, 2013

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Antidepressant Drugs May Also Treat SCLC

Antidepressant Drugs May Also Treat SCLC | Lung Cancer Dispatch | Scoop.it

Two drugs that are currently approved to treat symptoms of depression may also be effective against small cell lung cancer (SCLC). Researchers used bioinformatics, which combines mathematics and computer science to analyze large amounts of biological data, to pinpoint drugs likely to act on pathways that are important in SCLC. They identified the antidepressant imipramine (Tofranil) and the sedative/anti-nausea medication promethazine (Phenergan). Both drugs killed SCLC cells both in cell culture and in mouse models of chemotherapy-resistant SCLC. SCLC tumors arise from cells that are part of the hormone and nervous system, which may explain the effectiveness of these drugs. A new clinical trial will explore the effectiveness of desipramine (Norpramin), a drug similar to Tofranil, in SCLC.

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ScienceDaily | Sep 27, 2013

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Breast Cancer Drugs May Also Be Effective Against Some Lung Cancers

Breast Cancer Drugs May Also Be Effective Against Some Lung Cancers | Lung Cancer Dispatch | Scoop.it

A class of drugs already in clinical trials for breast and ovarian cancer, so-called PARP inhibitors, may also be effective against some forms of non-small cell lung cancer (NSCLC). Around half of all NSCLC tumors have low levels of ERCC1, a protein that helps repair damaged DNA. PARP inhibitors act by blocking a different DNA repair mechanism. This creates a one-two punch that kills the NSCLC tumor cells that are low in ERCC1, while healthy cells remain relatively unharmed. A recent cell culture study showed that PARP inhibitors like olaparib, niraparib, and BMN 673 killed ERCC1-deficient NSCLC cells, but not cells with normal ERCC1 levels.

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Cancer Research UK | Aug 12, 2013

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Gleevec May Help Preserve Fertility After Chemotherapy

Gleevec May Help Preserve Fertility After Chemotherapy | Lung Cancer Dispatch | Scoop.it

Women who undergo chemotherapy often lose their fertility because the drugs used damage or kill their oocytes—immature egg cells stored in the ovaries. However, a recent study suggests that adding the cancer drug imatinib mesylate (Gleevec) to chemotherapy treatment may protect oocytes. Researchers treated mouse ovaries with the chemotherapy drug cisplatin (Platinol) either by itself or in combination with Gleevec, then implanted them into host mice. The oocytes from Gleevec-treated ovaries still suffered DNA damage from the Platinol exposure, but unlike oocytes treated with just Platinol, they did not die. Previous research suggests that the surviving oocytes could repair the damage over time after chemotherapy treatment ends. These findings offer the hope that Gleevec may help preserve fertility in chemotherapy patients.

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Medical News Today | June 20, 2013

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Medical News Today | June 20, 2013

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Inhalable Chemotherapy May Offer Superior Lung Cancer Treatment

Inhalable Chemotherapy May Offer Superior Lung Cancer Treatment | Lung Cancer Dispatch | Scoop.it

A new drug delivery system attaches chemotherapy drugs to nanocarriers–microscopically tiny particles–to create an inhalable lung cancer treatment. Because this approach delivers drugs directly into the lung, it minimizes their effects on the rest of the body, potentially reducing side effects. The drugs also reach the lungs in their most potent form, without being degraded after injection into the bloodstream during transport to the lung. In addition to chemotherapy, the nanocarriers can also deliver another type of small particle, called siRNA, designed to combat drug resistance. In a recent study, this inhalable combination treatment drastically shrank lung cancer tumors implanted in mice, and resulted in 83% of the drug being delivered to the lung, compared to 23% when the drug was injected. However, further testing is necessary before this treatment can be investigated in human clinical trials.

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ScienceDaily | May 22, 2013

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Diabetes Drug May Help Fight Lung Cancer

Diabetes Drug May Help Fight Lung Cancer | Lung Cancer Dispatch | Scoop.it

The diabetes drug metformin may enhance the effectiveness of radiation therapy in non-small cell lung cancer (NSCLC), a recent study concluded. At doses similar to those used in diabetes treatment, metformin slowed the growth of NSCLC cell cultures and made them more sensitive to radiation. It also improved the tumor-shrinking effect of radiation on NSCLC tumors transplanted into mice. These observations suggest that metformin may help prevent or overcome the resistance to radiation that many lung cancer tumors exhibit. The researchers are now working to develop a clinical trial to investigate the benefits of metformin in lung cancer patients receiving radiation therapy.

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Cancer Research UK | May 1, 2013

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Iclusig Inhibits Mutant Proteins Found in Lung Cancer

The leukemia drug ponatinib (Iclusig) also appears to target mutant versions of two proteins involved in non-small cell lung cancer (NSCLC). This is supported by two recent studies in which Iclusig slowed the growth of cells with mutant RET and FGFR proteins. The drug also shrank tumors with RET mutations that had been grown in mice. Based on these findings, Iclusig manufacturer ARIAD Pharmaceuticals is planning a phase II clinical trial to investigate the drug's effectiveness against NSCLC with RET mutations. A phase II trial assessing Iclusig's effects in squamous cell carcinoma (SCC) of the lung with FGFR mutations is already underway at the Dana-Farber Cancer Institute, Boston, Massachusetts, and is currently enrolling participants.

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ARIAD Pharmaceuticals, Inc. | Apr 8, 2013

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PARP Inhibitors May Offer New Option in Lung Cancer Treatment

PARP Inhibitors May Offer New Option in Lung Cancer Treatment | Lung Cancer Dispatch | Scoop.it

A new class of drugs called PARP inhibitors could help patients with non-small cell lung cancer (NSCLC) who have become resistant to cisplatin (Platinol), a study suggests. Researchers found that Platinol-resistant NSCLC cells contain high levels of a protein called PARP1 in an unusually hyperactive form. PARP1 inhibitors killed these cancer cells and slowed the growth of Platinol-resistant NSCLC tumors implanted into mice. High levels of a protein called PAR predicted greater effectiveness of PARP inhibitors and may be a future biomarker for identifying patients who would benefit from the treatment.

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Medical News Today | Apr 3, 2013

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Antioxidants May Actually Speed Lung Cancer Growth in Some Cases

Antioxidants May Actually Speed Lung Cancer Growth in Some Cases | Lung Cancer Dispatch | Scoop.it

Antioxidants are chemicals that neutralize particles called free radicals that can damage DNA. Preventing such damage may help lower cancer risk for some people. However, tumors themselves can contain high levels of free radicals; by eliminating these free radicals, antioxidants may help cancer cells grow. In a laboratory, lung cancer cells treated with the antioxidants vitamin E and acetylcysteine (ACC) multiplied faster than untreated cells. Vitamin E and ACC also increased tumor growth and decreased survival time in mice with lung cancer. The so-called 'tumor suppressor' protein p53 can sense certain free radicals to detect cells with DNA damage and stop their growth. Antioxidants may interfere with this cancer-suppressing mechanism by reducing free radical levels. Taking antioxidants may therefore not be recommended for lung cancer patients and smokers.

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Medical Xpress  |  Jan 29, 2014

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E-Cigarette Vapor Promotes Cancer-Like Transformations of Airway Cells with Predisposing Mutations

E-Cigarette Vapor Promotes Cancer-Like Transformations of Airway Cells with Predisposing Mutations | Lung Cancer Dispatch | Scoop.it

E-cigarettes (electronic cigarettes that use a battery-powered system to deliver nicotine without producing smoke) are advertised as a safer alternative to tobacco cigarettes. However, very few studies have investigated how e-cigarettes affect lung function and lung cancer risk. Researchers examined human airway cells with mutations in the TP53 and KRAS genes, which are often mutated in the airways of current or former smokers at high risk of lung cancer. When the cells were exposed to e-cigarette vapor, they developed cancer-cell-like behaviors and gene expression changes very similar to what was seen when these cells were exposed to tobacco smoke. E-cigarettes may increase the risk of developing lung cancer in high-risk people, including current and former tobacco smokers.

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ASCO Post  |  Jan 8, 2014

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Timing Cancer Treatment for Maximum Effectiveness

Timing Cancer Treatment for Maximum Effectiveness | Lung Cancer Dispatch | Scoop.it

Our bodies follow a 24-hour 'biorhythm' that affects most of our biological functions. This fact forms the basis of cancer chronotherapy, which takes time of day into account to plan cancer treatment. Administering cancer drugs at the right time can double effectiveness while reducing toxicity up to fivefold. However, individual differences in biorhythms mean that the 'right time' varies from one person to another. In a recent study, researchers linked gene expression in mice with the time point at which the chemotherapy agent irinotecan (Camptosar) produced the least toxicity. They developed a mathematical model that predicts each animal's ideal time point based on the expression of two genes. In the future, they hope to develop similar tools to help predict the best time for cancer treatment in human patients.

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Medical Xpress  |  Nov 22, 2013

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Genetic Mutation May Offer New Treatment Target for Some Lung Cancers

Genetic Mutation May Offer New Treatment Target for Some Lung Cancers | Lung Cancer Dispatch | Scoop.it

DNA analyses of lung adenocarcinomas, a type of non-small cell lung cancer (NSCLC), found that some tumors contain a kind of mutation called a gene fusion in a gene called NTRK1. The mutation consists of NTRK1, which is involved in cell growth, merging with a different gene. As a result, the gene’s product, a protein called TRKA, is continuously 'switched on,' independent of the signals that normally activate it. Treating cell cultures of lung cancer cells containing the NTRK1 gene fusion with TRKA inhibitors suppressed their growth. Patients with gene fusions in another gene, ALK, experience tumor shrinkage in response to treatment with the ALK inhibitor crizotinib (Xalkori). Similarly, TRKA inhibitors may act as targeted therapies for lung adenocarcinoma patients with NTRK1 mutations.

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ScienceDaily | Oct 27, 2013

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Diabetes Drug Glucophage May Make Radiation Therapy More Effective

Diabetes Drug Glucophage May Make Radiation Therapy More Effective | Lung Cancer Dispatch | Scoop.it

Past studies have suggested that the diabetes drug metformin (Glucophage) may make lung cancer tumors more susceptible to radiation, and therefore make radiation therapy more effective. Researchers therefore analyzed the medical records of patients with locally advanced non-small cell lung cancer (NSCLC) who had been treated with radiation and chemotherapy. Sixteen of these patients had been taking Glucophage at the time. All of the Glucophage-treated patients are still alive and the cancer has returned in only two so far (an average of 10.4 months after the treatment)–better outcomes than what was seen in the patients who were not on Glucophage. Glucophage also made tumors more sensitive to radiation treatment in a mouse model of lung cancer.

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ScienceDaily | Oct 23, 2013

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New Drug May Overcome Resistance to Xalkori

New Drug May Overcome Resistance to Xalkori | Lung Cancer Dispatch | Scoop.it

The drug crizotinib (Xalkori) is used to treat non-small cell lung cancer (NSCLC) with mutations in the ALK gene. However, most patients develop resistance to the drug, usually because of further mutations in the ALK gene. A new ALK inhibitor drug, PF-06463922, may offer a solution. PF-06463922 blocked a variety of Xalkori-resistant mutant versions of ALK in cell cultures, and inhibited the growth of Xalkori-resistant ALK-mutant tumors in mice. PF-06463922 also combated tumor cells driven by mutations in ROS1, a gene closely related to ALK, in mouse models. Like Xalkori, PF-06463922 may therefore also be effective for NSCLC patients with ROS1 mutations. Finally, PF-06463922 was able to penetrate into the brain in multiple animal species–important because lung cancer often spreads to the brain.

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ScienceDaily | Oct 20, 2013

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Researchers Identify Critical Gene Involved in Lung Cancer Growth

Researchers Identify Critical Gene Involved in Lung Cancer Growth | Lung Cancer Dispatch | Scoop.it

Notch genes are a family of genes that are involved in cancer growth. However, they also control many other biological functions, so drugs blocking all Notch genes are severely toxic. Now, researchers have identified one specific member of this gene family that plays a particularly important role in at least some cancers. Inhibiting this gene, Notch1, prevented tumor growth and caused cancer cells to die in both cell culture and animal models of lung adenocarcinoma, a type of non-small cell lung cancer (NSCLC). Drugs selectively targeting Notch1 may offer a less toxic approach to halting lung cancer growth.

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Medical Xpress | Aug 29, 2013

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Indirect Approach May Finally Make Inhibition of Cancer Gene KRAS Possible

Indirect Approach May Finally Make Inhibition of Cancer Gene KRAS Possible | Lung Cancer Dispatch | Scoop.it

The KRAS gene is mutated in one-third of tumors and its importance in promoting the growth of cancer cells has been known for decades. However, efforts to develop a KRAS inhibitor have so far been unsuccessful. Now, researchers may have found a way to suppress KRAS indirectly using a drug called deltarasin. To function properly, KRAS needs to be attached to the cell's membrane, a process aided by the transport protein PDE-δ. Deltarasin blocks PDE-δ, preventing KRAS from anchoring to the cell membrane. A recent study showed that deltarasin reduced the growth of KRAS-mutant tumor cells both in cell culture and in a mouse model of pancreatic cancer.

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Medical Xpress | Aug 9, 2013

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Transcription Factor SALL4 Is New Kind of Target for Cancer Treatment

Transcription Factor SALL4 Is New Kind of Target for Cancer Treatment | Lung Cancer Dispatch | Scoop.it

Researchers at the Harvard Stem Cell Institute (HSCI) are pursuing a gene called SALL4 as a potential new target for cancer treatment. SALL4 encodes a transcription factor, a type of protein that modifies when and how much other genes get expressed. Until now, cancer therapies have not focused on transcription factors; instead, most cancer drugs act on kinases—proteins that modify other proteins. SALL4 is normally only expressed in embryos. However, it can become active again in adults and promote tumor formation. Active SALL4 is found in almost all cases of acute myeloid leukemia (AML), a type of blood cancer, as well as in many patients with other types of cancer, including lung cancer. In two studies, HSCI researchers found that blocking either the SALL4 gene itself or its protein product suppressed cancer cells and improved survival in mouse models of AML and liver cancer. The scientists are now hoping to develop cancer treatments that target SALL4.

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Medical News Today | Jun 19, 2013

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Timing of Radiotherapy Could Reduce Hair Loss

Timing of Radiotherapy Could Reduce Hair Loss | Lung Cancer Dispatch | Scoop.it

A new study suggests that mouse hair operates on a schedule–it grows quickly during the day and slows down at night to repair DNA damage. If human hair behaves similarly, the discovery could help cancer patients avoid an unpleasant side effect of chemotherapy: hair loss. The study found that mice lost 85% of their hair after morning radiation sessions, but just 17% following nighttime sessions; hair cells repaired the inflicted damage overnight. Cancer cells, however, replicate at the same speed regardless of time, so the time of treatment won’t alter its effectiveness. The researchers believe investigating circadian clocks in humans could lead to treatment programs that minimize collateral damage such as hair loss.

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Medical News Today | May 23, 2013

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Medical News Today | May 23, 2013

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ACE Inhibitor Protects Heart and Lungs from Radiation Damage in Rats

Lung and breast cancers are often treated with radiation, but repeated high doses can also harm healthy tissues in the lungs and heart. New research suggests that both organs can be protected during radiation with a drug called captopril, an ACE inhibitor that is commonly used to treat cardiovascular disease. Radiation causes fibrosis (excess connective tissue) in the heart, diminishing blood flow to—and so damaging—the lungs. However, captopril decreases fibrosis in irradiated hearts and, therefore, also protects the lungs in rats, researchers reported at the European Society for Radiotherapy and Oncology's 2013 forum. The researchers are now designing a clinical trial to see if captopril also protects against radiation damage in people.

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Science Daily│Apr 21, 2013

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Improved MET Inhibitors May Have Potential as Lung Cancer Treatments

Improved MET Inhibitors May Have Potential as Lung Cancer Treatments | Lung Cancer Dispatch | Scoop.it

MET, also known as c-Met, is a protein that normally occurs only at low levels in healthy tissues, but is overabundant and often mutated in many tumors, including non-small cell lung cancer (NSCLC). It is therefore a promising target for cancer treatments called MET inhibitors. However, currently available MET inhibitors also interfere with other proteins, leading to serious side effects and limiting their usefulness. In a recent study, researchers showed that the new MET inhibitors EMD 1214063 and EMD 1204831 are highly selective for MET only. The two drugs also shrank NSCLC tumors implanted into mice, suggesting that they may be promising treatments for NSCLC.

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Clinical Cancer Research | Apr 3, 2013

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