Research by Type:
| Lung Cancer Research |
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BACKGROUND AND CHALLENGES Lung cancer is the leading killer among all types of cancer in the United States. It is estimated that lung cancer accounts for about 14% of all new cancer cases in 2011, but will cause nearly 27% of all cancer deaths. Over the past three decades, little improvement has been achieved in extending the lives of lung cancer patients. In the late 1970's, about 37% of people survived one year or longer after initial diagnosis; now, three decades later, this number has only improved to 42%. But there is hope. NFCR funds numerous leading researchers who are committed to finding more effective strategies for preventing, diagnosing and treating lung cancer. Through their dedicated efforts to build risk prediction models, develop chemopreventive agents, identify cancer genes in early-stage lung cancer, design cutting-edge devices for monitoring drug response, and seek new strategies to overcome tumor drug resistance, NFCR scientists are leading the battle against the deadliest cancer. Building risk prediction models for smoking-related lung cancer NFCR scientist Waun Ki Hong, M.D., a world-renowned cancer researcher from the M.D. Anderson Cancer Center, has long been studying the role of smoking in lung cancer development. His research in this area is near completion and has provided insights into why only a subgroup of smokers are prone to have their DNA damaged by smoking and consequently develop lung cancer. By building risk models to predict the development of smoking-related lung cancer, Dr. Hong hopes that those who are deemed to be at high risk could take proactive measures early on that might prevent or delay lung cancer development. Dr. Hong's team has also initiated clinical research on the natural Indian curry spice, curcumin, to determine its potential in lung cancer chemoprevention (using drugs to prevent cancer). Dr. Hong's initial results on this agent are promising and further research may confirm its usefulness in cancer chemoprevention. Identification of gene signatures and biomarkers in early lung cancer Knowing the molecular events in early stage non-small cell lung cancer (NSCLC) will allow doctors to better predict the survival outcome of their patients. Patients will also benefit from a more personalized treatment option with agents that target the genes and their products-options that early-stage NSCLC patients greatly need after their initial surgery. Using a powerful tumor model comprised of various cancer cell lines, together with large databases of tumor tissues, the scientists in the Hong research team identified a robust six-gene signature that may be valuable in predicting survival of patients with a subtype of NSCLC. Importantly, Dr. Hong's research has unraveled a protein product of one of those genes, with potential to become a powerful biomarker for predicting progression and outcome of early stage NSCLC. Dr. Hong's research is leading the exploration of the progressive molecular changes in lung cancer that can be translated into chemoprevention and treatment of lung cancer-at the earliest stage-when patients need it the most. Personalized medicine for non-small cell lung cancer patients Dr. Waun Ki Hong initiated the BATTLE program, or Biomarker-Based Approaches of Targeted Therapy for Lung Cancer Elimination, to develop individualized targeted therapies for patients with advanced NSCLC that is resistant to chemotherapy. The BATTLE program included four clinical trials in which patients were assigned to the treatment drug to which they were most likely to respond based on their personal biomarker profiles identified through tumor biopsies. BATTLE is an important initiative to move personalized medicine forward for lung cancer patients, improving treatment efficacy for individual patients. Detecting one cancer cell in a billion Cancer cells in the blood are very rare - as few as 10 among eight billion normal blood cells. While the existence of these circulating tumor cells (CTCs) has been known for roughly 140 years, CTCs have eluded researchers because there has not been technology sensitive enough to efficiently capture them -- until now. NFCR scientist Daniel A. Haber, M.D., Ph.D., and colleagues at Massachusetts General Hospital Cancer Center have designed a new microchip-based device called the CTC-chip, which can trap and isolate even a minute number of CTCs from a spoonful of blood running through the business-card sized chip. There are three important potential benefits to this discovery. First, it may help physicians do a better job of monitoring how effective a patient's treatment is in real-time. An initial clinical trial showed that a lowering in the amount of CTCs in the blood correlated well with treatment effectiveness. Secondly, the use of the CTC-chip may help physicians make more timely treatment adjustments, and improve patient outcomes. A clinical trial involving patients with non-small cell lung cancer revealed that new genetic mutations can appear within 3 to 4 months following initial treatment, causing tumor resistance to the current therapy. Continuous tracking of such genetic changes in individual patients is essential for doctors to make timely treatment adjustments, but it would be almost unthinkable as a treatment modality if this had to be done through repeated, painful, and invasive tumor biopsy. The CTC-chip offers a very practical alternative through non-invasive blood testing. Finally, the latest research with the CTC-chip suggests it may potentially be used to screen CTCs in the blood stream to detect cancer at an earlier stage, long before it actually metastasizes to distant organs, opening a new door for cancer early detection and screening. Dr. Haber is currently optimizing the CTC-chip for large scale clinical application. His breakthrough technology may soon become a treatment option, dramatically changing the face of clinical care for patients. Determining which patients will respond to Taxol, one of the most widely used chemotherapy drugs in the world Taxol, a natural product from the yew tree, has been used to treat over a million cancer patients with lung, breast, and ovarian cancer. In fact, internationally known NFCR scientist, Susan Band Horwitz, Ph.D., at the Albert Einstein College of Medicine, discovered the molecular mechanism of Taxol-that it binds and inhibits tubulin, a protein crucial to cell growth. However, lung cancer cells alter the type of tubulin protein expressed and Taxol may inhibit these different proteins less effectively. Dr. Horwitz reasoned that various types of tubulin proteins expressed by cancer cells may cause the resistance to Taxol observed in many patients. To focus on this very important problem, she has recently developed new techniques that enable her team to isolate and identify the different types of tubulin expressed in lung cancer cells as compared to normal cells. Importantly, the scientists will be able to learn if different types of tubulin proteins have varying sensitivity to Taxol. Dr. Horwitz's research is of high impact as it may be possible, by analyzing the type of tubulin expressed in a patient's cancer cells, to determine if they will respond effectively to Taxol even before the onset of treatment. Development of a new targeted anti-cancer drug for patients with small cell lung cancer NFCR scientist, Alan Sartorelli, Ph.D., of Yale University School of Medicine, designed and synthesized laromustine, a promising new anti-cancer drug for patients with small cell lung cancer (SCLC) and several other types of cancer. To make laromustine even more effective, his team’s new design allows an inactive form of the drug to convert to the active, cell-killing form only after it enters a cancer cell but not in normal, healthy cells. This new drug may also allow targeting of metastatic lung cancer cells that have spread to distant sites in the body. With this innovative drug design, Dr. Sartorelli envisions that this new targeted drug will cause little toxicity while effectively treating patients whose lung cancer is resistant to existing therapies. NEXT STEPS: HOW YOU CAN HELP These NFCR-supported research projects hold great promise for improving the treatment and survival of lung cancer patients, or possibly preventing lung cancer in the first place. What our scientists need is research funding. NFCR is committed to providing research funding to the outstanding scientists in order to keep their very promising research moving forward. Click here to make a donation.
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