Glossary

A
Aclarubicin		An anthracycline believed to antagonize topoisomerase enzymes by preventing them from binding to and cutting DNA.
Alkylating Agent		Highly reactive chemicals that introduce alkyl radicals into DNA and thereby prevent their proper functioning. Many are used as anti-tumor agents, but most are highly toxic yielding a variety of unpleasant side effects.
Angiogenesis		The growth and development of blood vessels.
Anthracyclines		A member of a family of anti-cancer drugs that are also antibiotics.
Antibiotics		A substance that kills bacteria within the body.
Antidote		A substance that counteracts the effects of a poison.
Anti-metabolite		Substance which is chemically similar to the building blocks of DNA, purine and pyrimidine. By masquerading as these substances, anti-metabolites inhibit DNA synthesis by being built in to the DNA and disrupting the code.
Anti-tumor antibiotic		There are a variety of anti-tumor antibiotics exhibiting several different mechanisms of action. The most significant are topoisomerase chemotherapeutics that work by causing topoisomerase enzymes, which are enzymes that facilitate cell division in healthy cells by making temporary breaks in DNA, to punch permanent breaks in the DNA and kill cells.
Apoptotic gene		A gene which induces an orderly pattern of events which leads to the death of a cell.
Apoptosis		Programmed cell death.
B
Blood Brain Barrier		An assembly of partially permeable membranes separating the brain from the rest of the body.
C
Cancer		Any malignant growth or tumor caused by abnormal and uncontrolled cell division; it may spread to other parts of the body through the lymphatic system or the blood stream.
Cardiotoxicity		Toxicity that affects the heart.
Catalytic Inhibitors (of Topoisomerase II)		Antagonists of that group of enzymes, (topoisomerase enzymes) that untangle chromosomal DNA in the process of cell division.
Cell cycle		The cell cycle is an evolutionarily conserved and tightly regulated process for growth and division.
Chemotherapeutic		Description of the type of cancer treatment - in this case by drugs as opposed to e.g. treatment by surgery or irradiation.
Chromatin		The readily stainable substance of a cell nucleus consisting of DNA and RNA and various proteins.
Chromosomes		Structures within a cell nucleus that carry genetic information that determines the sex and characteristics an organism inherits from its parents.
Clonogenic assay		The measurement of the effect of an anti-proliferative agent against the formation of genetically identical cell colonies in soft agar.
CMO		Contract manufacturing organization. Company that offers large-scale drug production on behalf of pharmaceutical companies.
Combination therapy		A cancer treatment strategy that employs a variety of different chemotherapeutic agents simultaneously. Since each drug differs in mechanism and side effects, this approach may minimize the possibility of the patient developing a resistance to the therapy.
CRO		Contract research organization. A company that specializes in conducting clinical trials on behalf of other pharmaceutical companies.
Cytotoxic		Relating to substances that are toxic to cells.
D
DNA		The molecule that encodes genetic information. DNA is the genetic material of most organisms and usually exists as a double-stranded molecule in which two anti-parallel strands are held together by hydrogen bonds between adenine-thymine and cytosine-guanine.
Doxorubicin		An antibiotic used as an anti-cancer drug.
DUBs or deubiquitinase enzymes		Enzymes which are believed to prevent degradation and destruction of proteins by removing ubiquitination or survival signals from target proteins.
E


Enzyme		Any of several complex proteins that are produced by cells and act as catalysts in specific biochemical reactions.
Etoposide		A well-established chemotherapeutic agent that has demonstrated high efficacy in combination therapy with Topotect.
Extravasation		The leakage of drug from the vein into surrounding tissue. Depending on leaked drug the event can cause severe and cumulative tissue necrosis including serious damage to the skin, muscles and nerves.
F
FDA		Food & Drug Administration, the health Authorities in the US.
G
Gene expression		The process whereby the instructions in DNA are converted into functional activity within the cell.
H
Hematological		Of or relating to the blood. For example hematological cancers, originate from and are carried by blood cells.
Histone		A protein tightly packed with DNA into a compact form known as chromatin. Histones play an important role in regulating gene expression. For a gene to be expressed, other proteins known as transcription factors must bind to specific binding sites on the DNA. By ensuring that the DNA is tightly compacted into chromatin, histones restrict access of transcription factors to the DNA, and consequently restrict gene expression.
Histone deacetylase (HDAC)		HDAC is a transcription-regulating enzyme that is responsible for enhancing the growth and division of tumor cells.
HSP90		Heat shock protein (HSP 90) is a protein that appears to protect proteins in cancer and healthy cells from deterioration as a result of physical stress such as excessive heat or exposure to chemotherapy. HSP90 is believed to inhibit or reduce the efficacy of chemotherapy and prolong the life of cancer cells.
I

In vitro		A biological experiment conducted in test tubes, petri dishes, etc.
In vivo		An experiment or test on a compound in a test animal.
Irradiation		The use of ionizing radiation in the form of photons, electrons, protons as well as other sources to kill cancer cells and shrink tumors.
K
Kinase		Widely used abbreviation for phosphokinase, an enzyme which acts as a catalyst in the transfer of phosphate from ATP to another molecule, releasing energy. Kinases are also involved in a wide variety of intracellular signalling, and as such are the target for many therapeutic approaches.
L
Lymphomas		A group of diseases of unknown cause, characterized by painless, progressive enlargement of the lymphoid tissue.
M

Melanoma		A malignant tumor that develops from melanocytes, which are melanin-producing cells in the skin.
Metastases		Tumor which has spread out from the original place of the tumor.
Methylation		The process carried out by specific enzymes (methyl transferases) that positions methyl groups on, for example, specific bases of DNA. The presence of these methyl groups can stop some restriction enzymes cutting at that site, and in mammalian cells it is important in controlling genes.
Monotherapy		The use of a single drug or other therapy.
Monoclonal antibody drugs		An antibody preparation which is genetically homogenous and may be directed at a specific feature of the cancer cell.
MTT assay		Measurement of cell viability and proliferation through the reduction of the yellow tetrazolium salt MTT (dimethylthiazolyl diphenyltetrazolium bromide).
Multidrug resistance		The resistance of cancer cells to a range of anti-cancer drugs, usually caused by pumping of toxic drugs out of the cell before they can affect it.
Multiple Myeloma		A malignancy of the plasma cells that affects multiple sites within the bone marrow and secretes all or part of a monoclonal antibody.
O
Oncogene		A gene that normally directs cell growth. If altered, it can promote or allow the uncontrolled growth that typifies cancer. Alterations can be inherited or caused by environmental exposure to cancer causing substances.
Oncologist		A specialist who treats cancer patients.
Orphan Drug Status		A term which describes a drug with Orphan Drug Status granted by the FDA and/or the EMEA. Such status confers certain development, registration and marketing advantages for new treatments to be used in rare diseases or conditions, as detailed more fully in part IV - regulatory framework.
Out-licensing		A cooperation in which another company takes over the development process for a candidate drug.
P


Palliative treatment		Treatment, the sole aim of which is to remove or lessen the debilitating effects of, for example cancer.
Pivotal trial pH		A trial which could lead to registration of the investigated drug A common measure of the acidity or alkalinity of a solution. The p refers to the negative power to which ten is raised to give the concentration. The H refers to hydrogen ions. Thus pH3 is a concentration of 10^-3 molar H⁺ ions (acidic), while pH9 is a concentration of 10^-9 molar H⁺ ions (alkaline).
Phase I clinical trials		Establish the best way to give a new treatment to humans after it has been studied in the laboratory. The purpose is to determine the maximum tolerated dose or amount of the treatment and give answers about the best way to administer new drug candidates.
Phase II clinical trials		Establish if a drug candidate has the desired initial efficacy in patients suffering from a specific disease or condition. If such efficacy can be demonstrated, Proof of Concept has been achieved for the drug candidate.
Phase II/III clinical trials		A clinical trial of which, while run as a Phase II, the results can be used to seek marketing regulatory approval because of a combination of factors including the conclusiveness of the results and an obvious need to make the drug available to patients as soon as possible.
Phase III clinical trials		Establish the long-term efficacy and safety of the drug candidate in its final dose and formulation. These studies may involve thousands of patients who are treated during one to two years. Upon completion of the Phase III studies the drug candidate is filed with appropriate authorities for review and approval for launch.
Plant alkaloid		Plant derivative which prevents cell division from occurring by inhibiting the synthesis of microtubules which function to separate chromosomes in cell division.
Preclinical development		The phase of drug discovery and development which precedes testing of the drug in humans. Many studies carried out in this Phase are required by regulatory agencies before they will allow testing in man.
Predictive clinical models		A method of evaluating and predicting the efficacy of a potential drug on e.g. human cell lines or enzymes evolved in the laboratory prior to being tested on humans in a clinical trial.
Proof of concept		Statistical proof of a drugs efficacy in a relevant patient group.
S
Small cell lung cancer (SCLC)		A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer.
Solid tumor		A cancer that arises in an organ or tissue other than the bone marrow or immune system.
T
Temozolomide		A chemotherapy drug most commonly used to treat a type of brain tumor known as glioma.
Topoisomerase enzymes		A unique group of enzymes that untangle chromosomal DNA. Topoisomerases cut gaps in one strand of double-stranded DNA, pass the other strand through the gap, and subsequently reseal the break.
Topoisomerase chemotherapeutics		Antagonists of that group of enzymes, (topoisomerase enzymes) that untangle chromosomal DNA in the process of cell division.
Toxicology		The science of poisons and their effect on an organism.
Toxicology studies		The studies, in biological systems, of the undesirable and/or harmful effects of substances, and, in particular, specific formulations of drug candidates in development or established drugs, with administration of the test substance at much higher doses than would be used in clinical treatment.
Tumor suppressor gene		The "brake systems" which function to suppress cell proliferation.

U
Ubiquitination		The addition of a ubiquitin signal to a range of proteins to assist in the removal of damaged proteins and the maintenance of cell health.




Ubiquitination		The addition of a ubiquitin signal to a range of proteins to assist in the removal of damaged proteins and the maintenance of cell health.

Glossary

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