The research conducted in my laboratory focuses on developing improved protocols for the treatment of cancer. Clinicians have an arsenal of very potent drugs available for treatment of cancer. These drugs, however, lack specificity and often produce severe, life threatening, toxicities. Further, optimal therapeutic effects of any anticancer drug appear to be dependent on their use in a combination setting. Multi-agent therapy is the standard by which cancer is treated. Based on this understanding, research in my laboratory is designing methods and strategies for capturing the benefits of drug combination effects that are often first measured using cell based screening assays. Although basic research interests include evaluation of novel targeted anticancer drugs, my group is also comprehensively pursuing combinations of existing, already approved, cytotoxic agents. The latter studies will provide the proof of concept data needed to demonstrate the value of pursuing anticancer drug combination products. These products will be of particular interest when used with emerging targeted agents, but will also demonstrate the potential to develop new products that may consist of two or more targeted agents.

In order to achieve this, my research group embraces two fundamental principles: (i) drug combination products will be dependent on use of drug carrier technologies and (ii) drug combination products should achieve optimal therapeutic effects using better tolerated drug doses. I have extensive expertise on the use of liposome drug carriers for improving the specificity of anti-cancer drugs as well as enabling the use of some exciting new biologically active agents, such as therapeutically active antibodies, nucleic acid drugs (antisense oligonucleotides and siRNA) and therapeutically active peptides. In general terms, liposomes are small microscopic bags prepared from natural and synthetic lipids (fats). The therapeutic activity of conventional anti-cancer drugs can be improved, sometimes dramatically, when given intravenously trapped inside these lipid bags. Mechanistically, it has been suggested that liposomal drugs deliver more drug to tumors then conventional drug and development of this technology has been based on achieving improvements in drug delivery to sites of cancer growth. It is believed that delivery of liposomal drug carriers from the blood to interstitial sites within the tumor is due to characteristics of tumor blood vessels. In addition, my research clearly establishes that drug release from liposomes, whether in the blood compartment or within the tumor, can increase tumor cell exposure to anticancer drugs. Based on this understanding, my lab is now using drug carriers, such as liposomes, to provide the format to deliver combinations of drugs that are shown, via high content cell screening assays, to interact to achieve better than expect (synergistic) therapeutic activity.

Members

Faculty/Leaders

Staff

Dr. Nancy Dos Santos , PhD, MBA

Director, Investigational Drug Program

Kianne Silva Monteiro Rodrigues, PhD, MSc

Research Animal Technician

Post-Docs

Dr. Maryam Sharifiaghdam, PhD

Post Doctoral Fellow

Students/Trainees

Kevin Sun

PhD Student

Selected Publications

Histone Deacetylase Inhibitors Synergize with Catalytic Inhibitors of EZH2 to Exhibit Antitumor Activity in Small Cell Carcinoma of the Ovary, Hypercalcemic Type.

Molecular cancer therapeutics, 2018
Wang, Yemin, Chen, Shary Yuting, Colborne, Shane, Lambert, Galen, Shin, Chae Young, Santos, Nancy Dos, Orlando, Krystal A, Lang, Jessica D, Hendricks, William P D, Bally, Marcel B, Karnezis, Anthony N, Hass, Ralf, Underhill, T Michael, Morin, Gregg B, Trent, Jeffrey M, Weissman, Bernard E, Huntsman, David G

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours.

Nature communications, 2017
Xu, Hong, Di Antonio, Marco, McKinney, Steven, Mathew, Veena, Ho, Brandon, O'Neil, Nigel J, Santos, Nancy Dos, Silvester, Jennifer, Wei, Vivien, Garcia, Jessica, Kabeer, Farhia, Lai, Daniel, Soriano, Priscilla, Banáth, Judit, Chiu, Derek S, Yap, Damian, Le, Daniel D, Ye, Frank B, Zhang, Anni, Thu, Kelsie, Soong, John, Lin, Shu-Chuan, Tsai, Angela Hsin Chin, Osako, Tomo, Algara, Teresa, Saunders, Darren N, Wong, Jason, Xian, Jian, Bally, Marcel B, Brenton, James D, Brown, Grant W, Shah, Sohrab P, Cescon, David, Mak, Tak W, Caldas, Carlos, Stirling, Peter C, Hieter, Phil, Balasubramanian, Shankar, Aparicio, Samuel

Projects

Copper Drug Complexes: Development of a novel class drugs with significant potential for treatment of platinum insensitive cancers

One strategy that Dr. Bally has been using to develop drug candidates for use in treating cancer involves repurposing drugs utilized for the treatment of diseases other than cancer; illnesses such as malaria, fungal infections or even alcoholism. He wants to repurpose these drugs for use in patients with cancer because they have unusual and unexpected ways of affecting cancer cell growth and survival. Further these drugs are very active in cancer cells that are resistant (insensitive) to one of the most commonly used drugs available to oncologist- cisplatin.

Copper-drug complexes for use in the treatment of aggressive cancers

When some drugs bind to copper, they have anticancer activity in the lab. However, these copper-drug complexes need to be reformulated for human use. With the support of an Innovation Grant, Dr Marcel Bally developed the first injectable formulation of an anticancer copper-drug molecule. He will now create additional injectable copper-drug treatments based on several other drugs. He will then study the effectiveness of these new treatments in lung and ovarian cancers that resist chemotherapy, selecting the most powerful candidates for further study.

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