Therapeutic Focus

ImQuest Life Sciences will become a leader in the
development of exciting new drugs for unmet medical
needs throughout the world.

Cancer

Cancer Program - Our approach toward cancer research at ImQuest BioSciences is based on a natural progression of identifying, characterizing and understanding the activity of an anticancer compound or biologic. Depending on the amount of information available on your agent, all or some of these services may be useful to you. The program is structured with two key elements in mind – the ability to identify and validate the mechanism of action - key for targeted therapeutics, and a practical approach that is focused and supports product development.

Cell-based Anticancer Activity Screens

NCI-60 Tumor Panel -The NCI-60 tumor cells panel is a well-studied panel of established tumor cell lines of various organ and cell types. The panel has been extensively characterized and this information can be valuable in interpreting the activity of a compound. Broader panels containing up to 240 tumor cells lines can also be utilized when a larger database of information is desired.

Primary Tumor Panels - Primary tumor cell cultures derived from patient tumor explants represent a second tumor cell screening platform. While these screens cannot rely on the supporting information available for the NCI-60 panel, results obtained with primary tumor cells may be more representative of real-world results obtained in the clinical setting.

Cancer Stem Cells - Cancer stem cells are now generally accepted as important for the maintenance and spread of many important types of cancer. These tumor-generating cells are also generally refractive to treatment with anticancer agents. Demonstration of anticancer activity against cancer stem cells could be an important aspect of understanding your product.

• Complete or partial panel sets
• Custom panels
• Multiple endpoint available (SRB, XTT, ATP, apoptosis)
• GI50, TGI, and LC50 determinations


Mechanism of Action Studies

Expression Profiling - The activity of an agent against one or more of our cell panels together with knowledge of tumor gene expression signatures obtained using microarrays, can provide a basis for understanding how an anticancer agent selectively kills or inhibits cancer cells. Insight into the mechanism of action of a compound or biologic can also be obtained by comparing the changes in the expression pattern of tumor cells following treatment with the anticancer agent.

Proteomics - Many important cancer pathways are most easily identified and studied at the protein level rather than at the RNA level. This is true when protein function is regulated by post-translational modifications such as proteolytic cleavage, phosphorylation or ubquitination. Protein analyses can be focused on a specific protein of interest or be performed using an unbiased and broad survey of protein expression and modification.

Pathway validation - Cancer pathways implicated in the activity of an anticancer agent by expression profiling or proteomics approaches can be validated using methods appropriate to the proposed mechanism of action:

• Apoptotic pathway analysis
• Binding studies
• ELISA
• RT-PCR
• Immunohistochemistry
• Chromatin immunoprecipitation
• RNA knockdown using miRNA or siRNA
• Isogenic cell line pairs differing in a one or two directed gene mutations

Biomarker identification - Knowledge regarding the genomics, proteomics or mechanism of action of susceptible tumor cells can be used to develop companion biomarkers.  These biomarkers can be used to identify patient populations likely to respond to therapy as well as to monitor the anticancer effect in the preclinical or clinical setting. Preclinical validation of a biomarker can provide the rationale to incorporate that information during the clinical development of the agent.

• Protein and DNA markers
• Surrogate markers
• Plasma or tissue-based

Drug Combination Effects – Synergy and Antagonism - Clinically, nearly all anticancer agents are used in combination. By combining your agent with approved anticancer treatments or other experimental agents in vitro, quantitative drug-drug interaction effects such as synergy, antagonism and additive effects can be determined using the Median-Dose Effect model. Interactions characterized in vitro can then be supported with in vivo data obtained from mouse tumor models. Knowledge of the agent’s mechanism of action can be used to develop and test hypotheses regarding the mechanism of synergy and point the way toward improved combination therapies.

• Small molecule and biologics
• Constant or non-constant ratio approaches
• Isobolagram plots

Mouse Tumor Models - The ability of an anticancer compound or biologic to inhibit tumor growth or cause tumor regression in a mouse tumor model is an essential part of anticancer drug development. Mouse xenograft and syngeneic tumor models are available. Xenograft models employ an immune-incompetent mouse strain and allow the use of study human tumors. Syngeneic, and allogeneic, models are performed with immune-competent mice and allow the effects of the immune system on the anticancer therapy to be studied.

• Subcutaneous, intradermal, intracranial and peritoneal tumor models
• Metastatic tumor models
• Cancer stem cell models
• Drug combination effects
• Immune function/immunogenicity
• Specialized knockout strains available