Molecular oncology is an interdisciplinary medical specialty at the interface of

medicinal chemistry Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and developme ...

and

oncology Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''� ...

that refers to the investigation of the chemistry of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

and

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s at the molecular scale. Also the development and application of molecularly targeted therapies.

Main branches

Molecular oncology has identified genes that are involved in the development of cancer. The

research Research is " creative and systematic work undertaken to increase the stock of knowledge". It involves the collection, organization and analysis of evidence to increase understanding of a topic, characterized by a particular attentiveness ...

combined diverse techniques ranging from genomics, computational biology,

tumour A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

imaging Imaging is the representation or reproduction of an object's form; especially a visual representation (i.e., the formation of an image). Imaging technology is the application of materials and methods to create, preserve, or duplicate images. ...

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...

and

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

functional models to study biological and clinical

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...

s. The

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s produced by these

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s may serve as

targets ''Targets'' is a 1968 American crime thriller film directed by Peter Bogdanovich, produced by Roger Corman, and written by Polly Platt and Bogdanovich, with cinematography by László Kovács.Stephen Jacobs, ''Boris Karloff: More Than a Monster' ...

for novel

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

drugs and other cancer treatments, or imaging scans. Scientists use a range of techniques to validate the role of the novel candidate genes in the development of cancer. The ultimate aim is to translate these findings into improved treatment options for cancer patients.

Gene Targets

There are many different genes being researched for possible cancer therapies. Among the most studied are the p53 gene and the

PTEN gene Phosphatase and tensin homolog (PTEN) is a phosphatase in humans and is encoded by the ''PTEN'' gene. Mutations of this gene are a step in the development of many cancers, specifically glioblastoma, lung cancer, breast cancer, and prostate ca ...

. These genes are major regulators of the

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and sub ...

and other pathways involved in cellular and genomic integrity. By halting the cell cycle, these genes ensure that genetically damaged cells are not passing on that damage to daughter cells. The cell cycle may be paused and if the damage is severe enough, the p53 and PTEN gene pathways may signal for the death of the damaged cells. Both the p53 and PTEN genes are classified as

tumor suppressor A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or re ...

s because their pathways oversee the repair of cells that may replicate out of control with damaged genetic material, eventually leading to cancer growth if not kept in check.

Mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...

s in these genes are seen in more than half of human cancers.

Molecular Oncolytic Therapies

Immunotherapy

Immune

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...

is a targeted approach to cancer therapy where actual immune cells of the patient and their genes are manipulated to produce an anti-tumor response. The body's own

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...

is used to attack the tumor cells, therefore the immune system can naturally attack the specific cancer cells again to in the future if necessary. Many types of immunotherapies exist including bone marrow transplants,

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

therapies, and various manipulations of host immune cells to target and kill cancer cells. Cellular receptors, antigens, and cofactor molecules are some such cellular manipulations to target cancer cells.

''Chimeric Antigen Receptor T Cell''

Chimeric antigen receptor T cell In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specifi ...

immunotherapy (CAR-T), possibly combined with

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

s and

checkpoint inhibitor Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some cancers can protect the ...

s, are a regularly used form of immune gene therapy. CAR-T involves manipulation of a patient's natural

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s to express a chimeric antigen receptor. This receptor, now on millions of the patient's T cells, recognizes cancerous cells that express specific

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

s. Usually, the T cell antigen receptor is inactive but when the receptor recognizes a certain cancerous antigen, the physical structure of the T cell changes to destroy the cancer cell. This is a method of cancer treatment that works on the cellular and molecular level.

''Combining CAR-T with Checkpoint Inhibitors, Cytokines''

Some regulatory proteins, specifically immune

s, have been found to reduce the ability of T cells to multiply within the body. In order to optimize the efficacy of CAR-T gene therapy, these checkpoint inhibitors can be blocked to stimulate a robust anti-tumor immune response, spearheaded by the CAR-T cells. There are various known inhibitory receptors on the CAR-T cell; through manipulation of these receptors and the molecules that bind them, expression of the CAR-T cell can be amplified. CAR-T cells can also be combined with

s to improve the efficacy of the immunotherapy method. Cytokines are messenger molecules that can act on themselves, nearby cells, or distant cells. The signal pathways of these cytokines can be used to enhance CAR-T anti-tumor characteristics. For example, Interleukin 2 (IL2) is a cytokine that acts as a

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regul ...

for various immune system cells, including T cells. In regards to gene therapy, IL2 can be used to increase replication and dispersing of CAR-T cells throughout the body.

''Issues with CAR-T Therapy''

There is room for improvement with this gene therapy approach. Firstly, the antigens of interest expressed on the cancer cells may sometimes be expressed on regular body cells, too. This means the body's T cells will attack its own healthy cells instead of the cancer cells when the antigen is lacking specificity with just the cancer cell. A possible solution to this problem is to include two different antigen receptors on the CAR-T cells to make them even more specific. The second issue with the CAR-T immunotherapy approach is that it can cause cytokine release syndrome. This is when an excess of

pro-inflammatory Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...

factors are released by the immune system and can cause unpleasant side effects for the patient like

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

and a high

fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

Gene Therapy

In the past few decades, gene therapy has emerged as a targeted way to treat cancer. Gene therapy introduces foreign genetic sequences to diseased cells in order to change the

expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...

of these cancerous cells that are functioning with severely damaged genomes. Cancer cells do not behave like normal cells, so the methods for ridding the body of these cells are more complicated. Manipulation of the pathways controlled by certain genes and their regulators are a large branch of cancer research.

References

{{Medicine Medicinal chemistry Oncology Interdisciplinary subfields of medicine