Day 1 :
University of Texas Health Science Center at Houston, USA
Time : 10:00-10:45
Zhiqiang An is Professor of Molecular Medicine, the Robert A. Welch Distinguished University Chair in Chemistry, and Director of the Texas Therapeutics Institute at the UT Health Science Center at Houston. His laboratory focuses on breast cancer antibody drug resistance mechanisms and cancer antibody drug discovery Previously, he was Director of Biologics Research at Merck Research Laboratories. Dr. An received his Ph.D. degree from the University of Kentucky and his postdoctoral training at the University of Wisconsin-Madison. He is elected fellow of Society for Industrial Microbiology and Biotechnology (SIMB) and the American Academy of Microbiology (ASM).
The natural immune responses that patients develop to their own tumors, as well as therapeutic regimens employing the latest anti-cancer monoclonal antibodies, would reasonably be expected to suppress tumor growth. Yet, a perplexing resistance to both is widespread. The ineffectiveness of the immune system to prevail in these situations suggests that cancers possess tactics to evade antibodies that could otherwise eradicate them. With a clinical context in mind, we observed that tumor-associated protein-degrading enzymes can diminish, and in some cases negate, cell killing functions by inducing a single clip in a small part of the antibody structure. The structural modification is so subtle that it had not been previously recognized and would not have been anticipated to so profoundly impair the antibody. To be able to visualize and establish if such cleavage occurred in cancer, we had to develop innovative antibodies for that exact purpose. Indeed, the new antibodies readily enabled the visualization of antibody damage when incubated with cancer cells in the laboratory or within tumor tissues obtained from animals or human patients. More importantly, the same antibody tools possessed the additional and remarkable property of restoring the lost functions to the damaged antibodies. The “rescue” of lost function suggested that this could be exploited as a therapy in cases where tumors cause antibody damage in order to evade our immune system. This novel therapeutic strategy represents a potentially new direction in cancer immunotherapy.
University of Sydney, Australia
Keynote: : Pharmacological activity of an advanced formulation of curcumin for targeted therapy of triple negative breast cancer
Time : 11:05-11:50
Pegah Varamini is a lecturer and group leader in Cancer Theme within the Faculty of Pharmacy. She is the leader of Breast Cancer Targeting-Drug Delivery Group. Dr varamini was awarded the prestigious National Breast Cancer Foundation (NBCF) fellowship in Jan 2016. She completed her Doctorate degree in Pharmacy (PharmD) in May 2005 and was awarded her PhD degree in Medicinal Chemistry and Pharmacology in December 2012 (UQ, Australia). She won 2012 Dean’s Award for Research Higher Degree Excellence. Dr Varamini’s work was selected by the Australian Academy of Science in August 2016, resulting in her personal presentation at the inaugural Falling Walls Lab in Canberra (a gathering of 25 selected Australian and New Zealand researchers, entrepreneurs, engineers and innovators).
Breast cancer is the most common malignancy and the second leading cause of cancer-related death among Australian women despite existing progress in the development of novel therapeutic strategies. Triple-negative breast cancer (TNBC) accounting for 10-17% of all breast carcinomas, is an aggressive histological subtype. It represents an important clinical challenge because these cancers do not respond to the available targeted agents. Thus, there is an urgent demand for specific therapies that target other receptors that are overexpressed in TNBCs. We have designed and synthesized a novel drug delivery system, which targets curcumin to the breast cancer cells through a ligand of luteinizing hormone-releasing hormone (LHRH) receptors. LHRH receptors are overexpressed in breast cancer cells including MBC and TNBC cells while they are not expressed detectably in most visceral organs. We have taken advantage of this differential receptor expression by attaching a new derivative of the LHRH peptide (as a targeting moiety) to the outer surface of novel polymer nanoparticles. These nanoparticles encapsulate curcumin, a non-toxic plant extract that has recently attracted much attention in medicine due to its remarkable therapeutical actions. It is called the "next generation multipurpose drug" and is the active constituent of the Indian spice turmeric. However, it suffers from a very poor metabolic stability and bioavailabilty due to low water solubility. We have used an advanced formulation strategy to overcome hurdles to make it effectively used as a medication and also target it specifically to the TNBC cells via LHRH receptors.