Hot Topics at ASCO and Beyond: Navigating Key Terms in Medical Oncology
02 JUN 2022
With the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting on the horizon, we’ve developed a handy guide of key oncology terms to help those following the latest updates in the field.
Antibody-drug conjugates (ADCs)
Antibody-drug conjugates, or ADCs, are a class of targeted drugs that link a monoclonal antibody that targets specific cancer cells to an anti-cancer agent that destroys cancer cells to optimize the features of both components.
ADCs are able to deliver ‘deactivated’ cancer killing agents (cytotoxins) to specific cancer cells. Once in the tumor cell, the cytotoxin is released, after which it regains its full cancer-killing (cytotoxic) activity toward the targeted cancer cells, while potentially minimizing damage to healthy cells.1
A cell’s natural mechanism for programed cell death. It plays a critical role in development and the body’s normal function. Apoptosis eliminates any unnecessary or unwanted cells and is a highly regulated process. There are a wide variety of conditions that will result in this process becoming activated including DNA damage or uncontrolled cell proliferation. The prevention of cancer is one of the main functions of apoptosis. There are many ways that cancer cells can evade apoptosis. Typically, loss of control of the apopoptic pathway allows cancer cells to survive longer and gives more time for the accumulation of mutations which can increase the invasiveness of the tumor.2
Artificial intelligence (AI)
Software technologies that can program machines to act and think like humans, and perform tasks that normally require human intelligence, such as speech recognition, decision-making, and visual perception.3 Because AI algorithms learn differently than humans, they look at things differently. They can see relationships and patterns that escape us. This human and AI partnership offers many opportunities. Given the significant amount of complex data generated during cancer treatments, use of AI algorithms and reasoning can likely facilitate better diagnostic and predictive models, ultimately improving outcomes of cancer care.
Bispecific / Bifunctional antibodies
A bispecific antibody usually has two different antibody variable regions and carries out its functions by binding to two different cellular targets, whereas bifunctional antibodies, or bifunctional fusion proteins, are distinguished by having two separate and independent functions to treat disease.
Bispecific T-cell engagers (BiTEs)
BiTEs are a class of bispecific monoclonal antibodies currently under investigation as anticancer therapeutics. They are a type of fusion protein designed to harness the power of the immune system to treat cancer. BiTEs bring together T cells and tumor cells. They work to direct the immune system, more specifically the T cells’ cytotoxic activity, by binding to T-cell surface glycoprotein CD3 ε-chain (CD3) on T cells and an antigen on tumor cells. This activates T cells to kill tumor cells, but the T cells are only activated when both binding sites are occupied.4
A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Also called molecular marker and signature molecule.5
In cancer, a biomarker may be secreted by a tumor (or the body in response to the presence of the tumor) and its presence can aid diagnosis, treatment and also prognosis.
CAR-T (cell) therapy
A type of treatment in which a patient's own T cells (a type of immune system cell) are modified in the laboratory so they can attack cancer cells. T cells are taken from the patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR-T cells are grown in the laboratory and given back to the patient by infusion. Due to the newly engineered ability to recognize and bind certain protein(s) on the cancer cells, the T cells are able to destroy them. CAR T-cell therapy is being studied in the treatment of some types of cancer.5
Cell therapy (CT)
The injection or implantation of donor human cells to replace or repair damaged tissue and/or cells in a recipient host. Many different types of cells may be used as part of a therapy or treatment for a variety of diseases and conditions. Some of the cells used for CT include hematopoietic (blood-forming) stem cells (HSC), skeletal muscle stem cells, mesenchymal stem cells (adult stem cells that can differentiate into a variety of cell types), lymphocytes (a type of white blood cell used to combat infection), dendritic cells (antigen-presenting cells involved in the adaptive immune response), and pancreatic islet cells.6
Bio-molecules (generally antibodies) that block certain proteins (immune checkpoints) made by immune system cells, such as T cells (a type of white blood cell of key importance to the immune system), as well as some cancer cells. The checkpoint proteins control immune responses and can keep T cells from killing cancer cells, allowing the tumor or cancer cells to “hide” from the body’s immune system. When these proteins are blocked by checkpoint inhibitors, the “brakes” on the immune system are released and T cells are able to kill cancer cells better. Examples of checkpoint proteins found on T cells or cancer cells include PD-1/PD-L1 and CTLA-4/B7-1/B7-2. By using the body’s own immune system to recognize and fight a tumor or cancer cell, some immune checkpoint inhibitors are able to treat cancer.6
Companion diagnostics (CDx)
Companion diagnostics are assays or tests specifically developed to accompany certain drugs. As an essential component of personalized medicine, CDx can help identify the right patient population as well as avoid adverse drug reactions. CDx further aids doctors to identify patients who are at increased risk for serious side effects from certain medicines. Besides being commonly used in oncology, CDx are also helpful in other disease areas including muscular, cardiovascular, gastrointestinal and more.7
DNA Damage Response (DDR)
DDR is a collective term for all the DNA repair mechanisms a cell has in order to cope with damage of their genetic material. Cancer cells develop defects in a DDR system, which can enable them to grow in an uncontrolled way and spread throughout the body. DDR defects in cancer represent an “Achilles heel” which can be targeted in a variety of clinical settings.8
The study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself. Epigenetic changes affect how genes are read by cells, and subsequently whether the cells should produce relevant proteins.9,10
Germline / genetic testing
Typically inherited from a parent, a mutation found in any cell in the body is called a germline mutation. What we call hereditary cancers are caused by germline mutations and account for 5-10% of all cancers. Germline testing looks for these inherited mutations, and can be performed on blood, saliva or cultured fibroblasts (a type of cell that contributes to the formation of connective tissue). Germline testing can be used for a number of reasons: explain why the patient developed their current cancer; help identify targeted therapies to treat cancer; to indicate if patients are at an increased risk for additional, new cancers — allowing the patient to pursue enhanced screening or preventative surgeries to manage their risks; and, to identify if family members are at risk for hereditary cancer.11
Hot and cold tumors
“Hot” tumors are cancers that have been invaded by swarms of T cells (a type of white blood cell of key importance to the immune system), creating an inflamed tumor microenvironment. Although this response itself doesn’t kill the tumor, it enhances the mobility and functionality of already present T cells to act against the cancer.
“Cold” tumors, on the other hand, are cancers that, for various reasons, haven’t been recognized or haven’t provoked a strong response by the immune system. Immune T cells are unable to penetrate such tumors.12
Innate immune response (innate immunity)
An immunological system that provides the first line of defense against infection. Innate immune response consists of cells and mechanisms that attack invading pathogens in a non-specific manner. Innate immune response protects the host against bacteria, parasites, and other foreign particles, and limits their ability to spread throughout the body. It includes physical barriers such as skin and body hair, defense mechanisms such as gastric acid, saliva, and mucous, and general inflammatory responses that recognize pathogenic elements.13
The ability of a foreign substance to enter a person's body and cause an immune response. For example, when a virus enters a body, the immune system will react by creating antibodies designed to bind to the virus. As the immune system creates more virus-specific antibodies, the body is able to destroy all the invading virus particles and the person eventually gets better.14 Some of the antibodies may remain in the blood stream and may get reactivated during any future infections by the same virus.
A blood test performed to look for cancer cells that might be circulating in the blood or for pieces of DNA from tumor cells that are in the blood. A liquid biopsy may be used to help find cancer at an early stage. It may also be used to help plan treatment, to find out how well treatment is working, or if cancer has come back. In addition, it can help doctors understand the changes that may occur in a tumor by taking multiple samples of blood over time.5 A liquid biopsy may minimize the need for tissue biopsy, but is not available for all types of cancer.
Maintenance therapy is the treatment of cancer with medication, typically following an initial round of treatment. Maintenance treatment may include chemotherapy, hormonal therapy, or targeted therapy.
Maintenance treatment is generally used to prevent or delay the cancer’s return if the cancer is in complete remission after initial treatment. In this situation, maintenance treatment may stop, or delay, the cancer coming back. Another reason it may be used is to slow the growth of advanced cancer after initial treatment. In advance cancer, it is not used to cure the cancer, but it may lengthen a person’s life.
Although not new to cancer treatments, it is used more often now than in the past because: the number of effective drugs for use in maintenance has increased; newer medications may often have less side effects so people can take them for longer; and, maintenance therapy can help certain types of cancers more than others — helping people with those specific cancers live longer.15
The collection of all the microorganisms, bacteria, and viruses that live in a given environment, including the human body or part of the body, such as the digestive system.5
Patient-derived xenograft (PDx)
This term refers to tumor tissue that has been taken from a patient and implanted into immune-deficient animal models. PDx creates an environment that allows for the natural growth of cancer and its monitoring, allowing drug testing before they are given to the patient. Patient-derived xenografts may be used to help plan treatment and learn what drugs the tumor graft either responds to or is resistant against. They are also being used in the development of new cancer drugs.5
An approach to patient care that allows doctors to select treatments that are most likely to help patients based on a genetic understanding of their disease. The idea of precision medicine is not new, but recent advances in science and technology have helped speed up the pace of this area of research. Precision medicine allows treatments to be tailored to target genetic changes in an individual’s cancer, sparing patients from receiving treatments are not likely to help and potentially minimizing treatment side effects or toxicity.16
Biomarkers used to identify individuals who are more likely than similar individuals without the biomarker to experience a favorable or unfavorable effect from exposure to therapeutic intervention (e.g., drugs, biologics) or an environmental agent.17
Biomarkers used to identify the likelihood of a clinical event, disease recurrence, or progression in patients who have a particular disease or medical condition.9
Combination products, also known as fixed-dose drug combinations (FDCs), are combinations of two or more active drugs in a single dosage form. The rationality of FDCs should be based on certain aspects such as:
- The drugs in the combination should act by different mechanisms.
- The movement of the drugs within the body (pharmacokinetics) must not be widely different.
- The toxicity or detrimental effects of the combination ingredients should not exceed the sum of the individual effect. 18,19
Cancer drugs can be more effective when given in combination. By using drugs that have different mechanisms, the cancer cells are killed in more than one way, increasing the effectiveness of the treatment, and reducing the likelihood of resistance. When drugs with different effects are combined, each drug can be used at its optimal dose, without intolerable side effects.13
Treatment that uses drugs or substances to identify and attack specific types of cancer cells, while causing less harm to normal cells. Some targeted therapies can block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells. Other types of targeted therapies help kill cancer cells by activating the body’s own immune system or by delivering toxic substances directly to the cancer cells. Most targeted therapies are small molecule drugs or antibodies, and they may have fewer side effects than other types of cancer treatment.2
Translational science / translational medicine
An interdisciplinary branch of the biomedical field supported by three main pillars: benchside, bedside, and community.
- Benchside refers to clinical and/or biomedical research discoveries and applications conducted by medical practitioners and scientists.
- Bedside refers to practicing clinical methodologies on patients and gathering feedback and input from the recipients.
- Community is represented by healthy populations and patients, as well as medical practitioners, that can provide input, background, context, and more to medical and public health issues.20
The normal cells, molecules, and blood vessels that surround and feed a tumor cell. A tumor can change its microenvironment, and the microenvironment can affect how a tumor grows and spreads.5 Understanding the tumor microenvironment allows for the selection of targeted, effective cancer treatments that can alter the tumor microenvironment in order to prevent the growth and spread of a tumor.
Tumor mutational burden (TMB)
The total number of mutations (changes) found in the DNA of cancer cells. Knowing the TMB can help plan the best treatment regimen for some cancers. For example, tumors that have a high number of mutations appear to be more likely to respond to certain types of immunotherapy. TMB is being used as a type of biomarker.5
1 ADC Review. Journal of Antibody-Drug Conjugates. What are antibody-drug conjugates? Available at: https://www.adcreview.com/the-review/antibody-drug-conjugates/what-are-antibody-drug-conjugates/
2 Int J Mol Sci. 2018 Feb; 19(2): 448 Apoptosis: a target for anticancer Therapy. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855670/
3 Market Business News. What is Artificial Intelligence? Definitions and Examples. Available at https://marketbusinessnews.com/financial-glossary/artificial-intelligence/
4 Journal of Clinical Oncology 34, no. 10 (April 01, 2016) 1131-1133.Available at: https://ascopubs.org/doi/10.1200/JCO.2015.64.9970
5 National Cancer Institute. NCI Dictionary of Cancer Terms. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms.
6 AABB. Facts About Cellular Therapies. Available at http://www.aabb.org/aabbcct/therapyfacts/Pages/default.aspx
7 Alliance of Advanced BioMedical Engineering. Companion Diagnostics for Oncology. Available at https://aabme.asme.org/posts/companion-diagnostics-for-oncology
8 Giglia-Mari, Giuseppina et al. “DNA damage response.” Cold Spring Harbor perspectives in biology vol. 3,1. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003462/..
9 What is Epigenetics? Available at https://www.whatisepigenetics.com/what-is-epigenetics/
10 Fuchs, O. (2016). Epigenetics and epigenetic therapy of myelodysplastic syndromes. Available at: https://www.researchgate.net/publication/316062333Epigeneticsandepigenetictherapyofmyelodysplasticsyndromes
11 UTSW Cancer Genetics. Somatic and Germline Testing Fact Sheet. Available at: https://s3-us-west-2.amazonaws.com/utsw-patientcare-web-production/documents/SomaticvsGermlineFactSheet.pdf
12 Dana-Farber Institute. Enhancing Immunotherapy: The Race to Make “Cold” Tumors “Hot.” Available at https://blog.dana-farber.org/insight/2018/06/enhancing-immunotherapy-race-make-cold-tumors-hot/
13 Khan Academy. Innate immunity. Available at https://www.khanacademy.org/test-prep/mcat/organ-systems/the-immune-system/a/innate-immunity
14 Study.com. What Is Immunogenicity? Available at https://study.com/academy/lesson/what-is-immunogenicity-definition-role-in-blood-transfusions.html
15 ASCO. Cancer.Net: Understanding Maintenance Therapy. Available at: https://www.cancer.net/navigating-cancer-care/how-cancer-treated/understanding-maintenance-therapy
16 National Cancer Institute. Precision Medicine in Cancer Treatment. Available at https://www.cancer.gov/about-cancer/treatment/types/precision-medicine. Last accessed April 2019
17 Food and Drug Administration (US); 2016-. Understanding Prognostic versus Predictive Biomarkers. 2016 Dec 22. Available at https://www.ncbi.nlm.nih.gov/books/NBK402284/
18 Gautam, Chandler S, and Lekha Saha. “Fixed dose drug combinations (FDCs): rational or irrational: a view point.” British journal of clinical pharmacology vol. 65,5 (2008): 795-6. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2432494/
19 Gale RP. Merck Manual. Combination Cancer Therapy. Available at https://www.merckmanuals.com/home/cancer/prevention-and-treatment-of-cancer/combination-cancer-therapy
20 Cohrs, Randall J.; Martin, Tyler; Ghahramani, Parviz; Bidaut, Luc; Higgins, Paul J.; Shahzad, Aamir. "Translational Medicine definition by the European Society for Translational Medicine". New Horizons in Translational Medicine. Available at https://www.sciencedirect.com/science/article/pii/S2307502314000782?via%3Dihub