Texas A&M Pharmacy Researcher Fights Cancer, Pain With New Cannabinoid Receptor Drug

The research focus of assistant professor of pharmaceutical sciences Dr. Dai Lu, Ph.D., and his team at the Texas A&M Health Science Center Irma Lerma Rangel College of Pharmacy, is on relieving the pain and suffering associated with multiple serious diseases and disorders, such pancreatic cancer, Alzheimer’s disease and traumatic brain injuries, as well as metabolic diseases like diabetes and obesity. Dr. Lu is collaborating with scientists nationwide in his quest to discover new ways to battle illnesses that cripple family and national budgets.

Research conducted at Dr. Lu’s lab is primarily concentrated on the interface of organic/medicinal chemistry and biomedical sciences. Within that broad context, the lab’s objective is the discovery of novel small-molecule drug entities and protein/polymer-based nanomedicine for cancer and protein-misfolding related disorders, such as Alzheimer’s disease, Parkinson’s disease and type II diabetes, etc. Therapeutic targets for research projects include microtubule, protein kinases, cannabinoid receptors, acetylcholinesterase, and certain amyloidal proteins. In chemical matters, natural products and their derivatives, as well as some hits from structure-based drug screening, are employed in the lab to identify novel leads for synthesizing and developing potential therapeutic agents to treat and manage the above diseases. Organic synthesis, drug-screening through bioassays, and nanofabrication are three key components of his lab’s research technologies. Currently, four projects are under investigation in Dr. Lu’s laboratory by a team of researchers including post-doctoral research associates Dr. Hamed Aly-Ismail and Teresa Olszewska.

DrDaiLuPrior to his coming to Texas A&M Rangel College of Pharmacy, Dr. Lu was an Instructor of Neurology at Harvard Medical School (2007-2011), and Senior Chemist at the Center for Neurologic Disease, of Brigham and Women’s Hospital & Harvard Medical School (2006-2011).

A TAMHSC Vital Record release by Cheri Shipman notes that Dr. Lu’s father died of pancreatic cancer in 2003, and that the hopeless and helpless feeling he experienced at his father’s bedside influenced his commitment to search for an effective cure for pancreatic cancer, which is one of the deadliest types of cancer.

Disabling pain together with malnutrition and jaundice are the most common symptoms in patients with pancreatic cancer, so pain management is one of the most important and difficult aspects of palliative care for inoperable pancreatic cancer. Approximately 90 percent of patients ultimately develop severe or intractable pain that quickly leads to deterioration of the quality of life and performance status of pancreatic cancer patients, most of whom at present are diagnosed at a late stage because symptoms of the disease do not appear until it is well-advanced, with the the tumor having grown to significant size. By that point, a cure is not feasible because the cancer will have already spread beyond the pancreas to other organs. According to the American Cancer Society, one-fifth of Americans diagnosed with pancreatic cancer survive for a full year, and 94 percent die within five years. Most pancreatic cancers are exocrine tumors. Pancreatic neuroendocrine tumors, or islet cell tumors, are less common but can often have a better prognosis.

DrsDaiLuHamedAlyIsmaillab“There are no indications that we cannot manage pancreatic cancer as we have done with other types of cancer such as colon and breast cancer,” Dr. Lu comments in the release. “There are just more challenges because pancreatic cancer is a highly invasive malignancy and the metastatic cancer cells are very resistant to currently available chemotherapies.” He also emphasizes that better treatments and, ultimately, cures for people with diseases like pancreatic cancer begin with scientific research.

Ms. Shipman’s report says that Dr. Lu has been working to find new types of chemotherapeutic drugs that both kill pancreatic cancer and suppress the cancer pain at the same time by targeting a special G-protein coupled receptor that belongs to the biological system responsible for the effects of Tetrahydrocannabinol (THC), a compound derived from some varieties of cannabis (hemp) or made synthetically, that is the primary psychoactive agent in marijuana and hashish. Dr. Lu says pancreatic cancer cells have more type 2 cannabinoid receptors than do healthy cells. Consequently, drug molecules that selectively activate this receptor can induce cancer cell death without affecting normal pancreatic cells, noting that when given to mice with pancreatic tumors, the molecule prevented tumor growth and suppressed the spread of cancer to healthy organs. Meanwhile, this class of compounds also generates painkillers comparable to morphine’s pain killing effect. The TAMHSC release says that Dr. Lu’s research, in collaboration with other researchers, has yielded promising results in the testing stage, and the drug development stage will commence with grant support from state and federal resources in the next few years.

Dr. Lu’s lab is also researching new ways to treat acute and chronic brain disorders such as traumatic brain injury and Alzheimer’s disease, investigating a drug that can augment the effects of some of the brain’s own molecules that can prevent inflammation before or after injury that are also linked to the biological system responsible for cannabis effects. Recently, the lab has discovered new molecules that potentially can protect the brain from traumatic and inflammatory injuries, although these molecules are in the early drug discovery stage. Dr. Lu’s research is currently pending financial support from the National Institutes of Health and the Department of Defense.

Dr.LuLab

The TAMHSC release cites recent data from the Centers for Disease Control and Prevention showing that approximately 1.7 million people sustain a traumatic brain injury annually, direct and indirect costs of which are estimated at approximately $48.3 billion annually.

“Given the enormous impact of traumatic brain injury on this nation, our research may someday help millions of people including men and women who serve in military forces and suffer from post-traumatic stress disorder,” Dr. Lu is cited commenting.

The Texas A&M Rangel College of Pharmacy opened its doors to students in 2006 to meet a critical need in the South Texas community where there is a shortage of pharmacists. Today, 103 out of 309 of the college’s graduates have returned to South Texas to help underserved populations. The college’s leadership strives to entrench a culture of excellence, education, research, practice and patient care to each professional student enrolled. Guided by a set of core values referred to as five-C’s (care, concern, courtesy, compassion and competence), the Texas A&M Rangel College of Pharmacy is dedicated to advancing the profession of pharmacy, and to enhance the quality of peoples’ lives in South Texas, Texas and beyond. It is ranked in the Top 50 for pharmacy programs in the country within a record time, as per the recent US News and World Report rankings.

Photos courtesy of Texas A&M Health Sciences Center.

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