Recurrent cancer is any form of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

that has returned or recurred when a fraction of primary

tumor cells 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 ...

evade the effects of treatment and survive in small spaces that are undetectable by diagnostic tests. The initial

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 ...

may become the site of cancer’s return or it may spread to another part of the body. These surviving cells accumulate various genetic changes over time, eventually producing a new tumor cell. It can take up to weeks, months, or even years for cancer to return. Following surgery and/or

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...

, certain tumor cells may persist and develop resistance to treatment and eventually develop into new tumors. The rate of cancer recurrence is determined by many factors, including age, sex, cancer type, treatment duration, stage of advancement, grade of original tumor, and cancer-specific risk factors. If recurrent cancer has already moved to other body parts or has developed chemo-resistance then it may be more aggressive than original cancer. In general, the severity of cancer increases with a shorter duration of time between initial treatment and its return. Cancers with the highest recurrence rates include

Glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...

with a recurrence rate of almost 100%, Epithelial ovarian cancer with a recurrence rate of 85%, and

Bladder cancer Bladder cancer is the abnormal growth of cells in the bladder. These cells can grow to form a tumor, which eventually spreads, damaging the bladder and other organs. Most people with bladder cancer are diagnosed after noticing blood in thei ...

with a recurrence rate of 30-54%

Types

There are three types of recurrent cancers: * Local recurrence - Cancer returns to the same original site. * Regional recurrence - Cancer is detected in tissue or lymph nodes near the original site. * Distant recurrence - Cancer has been detected in tissue far from the original site. Also known as metastatic recurrence.

Causes

Cancer stem cells

Cancer stem cells (CSC) are a small population of the entire tumor cell mass, that are responsible for early formation, progression, and recurrence of cancer. It also contributes to

drug resistance Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is ...

. CSCs are thought to originate from normal

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...

s, progenitor cells or differentiated cells as a result of cumulative genetic

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 or viral replication, ...

and subsequent genomic instability. They are found in the tumor microenvironment's specialized niches. CSCs have so far been found in a variety of tumors, including those of the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

breast The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...

ovary The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/ oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are end ...

head and neck This article describes the anatomy of the head and neck of the human body, including the brain, bones, muscles, blood vessels, nerves, glands, nose, mouth, teeth, tongue, and throat. Structure Bones The head rests on the top part of the vertebr ...

, etc. CSCs have the ability of self-proliferation just like regular stem cells. A single CSC can divide asymmetrically into one CSC and one differentiated tumor cell. The tumor is majority made up of the latter cells. In some cancers CSCs are quiescent for long period of time, making them ineffective to the treatment. Therefore, even decades after the primary cancer has been fully treated, the reactivation of the inactive CSCs may lead to tumor recurrence.

Neosis

Hypoxia, chemotherapeutic agents, and

radiation In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or a material medium. This includes: * ''electromagnetic radiation'' consisting of photons, such as radio waves, microwaves, infr ...

can generate Polyploid Giant Cancer Cells (PGCC). Some PGCCs have the ability to undergo neosis, which is characterized by nuclear budding

karyokinesis Mitosis () is a part of the cell cycle in eukaryotic cells in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis is an equational division which gives rise to genetically identical cells in which the ...

, asymmetric intracellular cytokinesis and the generation of

Raju cells The Raju are a Telugu caste found mostly in the Indian state of Andhra Pradesh. Etymology and Early references ''Raju'' is a Telugu language variant of the Sanskrit title ''Raja'', a term for a monarch or princely ruler. Cynthia Talbot des ...

, which are tiny mononuclear cells having stem cell like characteristics. These cells play a role in cancer recurrence and therapy resistance.

Phoenix rising

Phoenix rising is a process by which dead cells send signals that promote growth and division, generating new cells. After a tissue injury, stem cells present in and around the injured tissue play a crucial role in replenishing the damaged ones. It is theorized that molecules released from wounded cells trigger stem cells' migration to that site, followed by differentiation and proliferation. Through the process of

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

, the dying tumor cells provide growth signals and repair radiation-damaged tumors. PGE2 is released by apoptotic cells in a caspase-dependent manner, which aids cancer stem cells and cancer progenitor cells in expanding and multiplying.

Cell stress and dormancy

Cancer recurrence (relapse) is ascribed to malignant cells that evade therapy: small numbers of cancer cells may remain undetected, and dormant, pausing their proliferation for long time. This can occur also by mechanisms different from cell cycle quiescence. In fact, the effects of therapy that kills most cancer cells, may cause a few of them to pause proliferation instead of dying. While the precise mechanism of growth arrest is not entirely clear and may not be uniform across cancer cases, malignant cells that survive chemotherapy make several metabolic adaptations and possess altered configuration of key positions of their chromatin, the material that packages their DNA. This has as result that certain conditions can trigger expression of genes that reignite cancer cell growth, causing proliferation, and additionally these conditions may trigger aberrant expression of genes that cause changes in the host tissue, which also permit cancer growth.

Diagnosis

Early diagnosis of recurrence is important and can improve the prognosis and survival of patients with cancer. Depending on the primary cancer type, several laboratory and imaging tests, as well as numerous invasive procedures, are used for the diagnosis of recurring cancers.

Malignant tumors 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 ...

develop and secrete biologic chemicals known as

tumor marker A tumor marker is a biomarker that can be used to indicate the presence of cancer or the behavior of cancers (measure progression or response to therapy). They can be found in bodily fluids or tissue. Markers can help with assessing prognosis, s ...

s that are detectable in the bloodstream. These markers might ideally be used to screen for cancer, diagnose it, and track how effectively it responds to treatment.

Treatment

The inherent limits of current cancer therapy approaches usually result in treatment failure.

Chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

and

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

resistance is a common factor in the failure of treatment for many cancers. Additionally, because most treatments cannot completely eradicate CSCs, many methods that are not adequately selective against CSCs might be harmful to healthy tissues, and patients frequently run the risk of recurrence and

metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

. Recent years have seen the development of numerous treatments with the goal of eliminating CSC. Targeting CSC surface markers, the ABC cascade, the microenvironment, or signal cascades could all help kill CSCs. There are numerous drugs targeting these markers or pathways, which are being tested in clinical trials. The treatment varies from cancer to cancer and patient to patient.

References

{{reflist Cancer