An OVERVIEW of CANCER

An OVERVIEW of CANCER

CANCER, CAUSES OF CANCER, CANCER GENES, TREATMENTS OF CANCER

The cancer word comes from the Greek word “karkinos” which is identified by Hippocrates. The first founded cancer is in ancient Egypt about 1600 B.C which is founded in manuscript. The first recorded case of cancer(breast) from ancient Egypt in 1500 B.C. and no treatment was recorded. But, it is known from manuscripts that it was surgically removed from the body.

What is Cancer? and Cause of Cancer

Cancer develops when normal cells begin to grow out of control. Cancer cells continue to grow, divide instead of dying, they form new abnormal cells. People can also inherit damaged DNA from parents, which accounts for inherited cancers. Cancer could be caused by chemicals (carcinogens), radiation, viruses and also inherited from ancestors. Generally, cancer cells develop from normal cells due to damage of DNA. Most of the time when ever DNA was damaged, the body is able to repair it, unfortunately in cancer cells, damaged DNA is not repaired. Most carcinogens were damage the DNA, which led to abnormal growth of cells. The risk of developing many types of cancers can be reduced by changes in lifestyle by quitting smoking and eating low fat diet.

Genetic

Bowel cancer 

  • APC gene -> FAP(Familial adenomatous polyposis)
  • MYH(MUTYH) gene -> MAP(MYH associated polyposis) -> have 2 mutated copy of MYH gene
  • MLH1, MSH2, MSH6, PMS2 -> Lynch sendrome(Hereditary non polyposis colon cancer(HNPC))
  • STK11 -> PJS(Peutz Jeghers syndrome)
  • SMAD4, BMPR1A -> JPS(Juvenile Polyposis Syndrome)

Breast cancer

  • BRCA1, BRCA2 -> increases the risk of ovarian cancer, 70% of women with the faulty of BRCA genes develop breast cancer by the age of 80. 
  • TP53 -> Li Fraumeni syndrome
  • control cell division, a type of tumor suppressor gene.
  • PTEN -> Cowden syndrome
  • SNPs(Single nucleotide polymorphisms) -> increases the risk of breast cancer

Kidney cancer

  • Kidney cysts -> VHL syndrome
  • TSC1, TSC2 -> Tuberous sclerosis(TS)
  • FLCN(aka BHD) -> Birt Hogg Dube syndrome(BHDS)
  • MET -> Isolated hereditary papillary reneal cell cancer(HPRCC)

Melanoma

  • A type of skin cancer. Being too much influence of UV by sunlight or any other external factors is the main cause of this cancer type.
  • Familial atypical multiple mole melanoma syndrome(FAMMM)
  • CDKN2A

Ovarian cancer

  • BRCA genes -> a faulty in either BRCA1 or BRCA2 increases the risk of breast cancer
  • MLH1, MSH2, MSH6, PMS2 -> Lynch syndrome(HNPCC)

Pancreatic cancer

  • Doesn’t have specific gene faulty that specifically affects the pancreatic cancer. But BRCA2, STK11, MLH1, MKSH2, MSH6, PMS2, FAP, MEN1 are controlled to detect the presence of pancreatic cancer.

Prostate cancer

  • BRCA2 
  • BRCA1, Lynch syndrome -> not surely affects, but there are some studies

Retinoblastoma(Eye cancer)

  • RB1

Thyroid cancer

  • MEN(many types of MEN gene)
  • MEN2a, MEN2b -> Medullary thyroid cancer

Womb cancer

  • MLH1, MSH2, MSH6, PMS2 -> Lynch syndrome(HNPCC)

Scientist discovered 2 important gene families which are oncogenes and tumor suppressor genes in 1970s. Both oncogenes and tumor suppressor genes that are damaged by chemicals or radiation.

  • Oncogenes are formed by the mutations of proto-oncogenes which control cell division and differentiation. They cause normal cells to grow out of control.
  • Tumor suppressor genes control cell division, DNA repair and inform cells when to die. When a tumor suppressor gene doesn’t work properly, cells can grow out of control, which can lead to cancer.

Age

Cancer can be considered an age-related disease because the incidence of most cancers increases with age, rising more rapidly beginning in midlife. Age also can be considered a surrogate measure for the complex biological processes associated with aging. However, aging, the process of getting older, can be distinguished from age-associated diseases. Paradoxically, adults with the longest longevity are less likely to develop cancer. Thus, aging can be viewed as a natural process, not pathology, and old age does not necessarily lead to cancer.

If the environmental factors that influence these biologic mechanisms8 can be modified, the rate of aging may be slowed and the onset of cancer delayed or even prevented.

Cancer is most common in people over the age 60. The most common cancers in older people are skin, lung, colorectal, breast (in women), and prostate (in men). Many cancers in older adults are linked to lifestyle-related risk factors (such as smoking, being overweight or obese, or lack of physical activity) or to other environmental factors. A small part of these people influenced by genetic factors such as mutations and being inherited from their parents.

Cancer which develops in young ages is generally rare. It is mostly related to gene changes or inherited genes more than environmental risk factors and lifestyle.

The most common cancers in young adults are:

  • Breast cancer It’s rare before age 30, but it becomes more common as women age
  • Lymphomas (non-Hodgkin and Hodgkin) Hodgkin lymphoma is most common in 2 age groups: early adulthood (age 15 to 40, usually people in their 20s) and late adulthood (after age 55) Non-Hodgkin lymphoma (NHL) is less common than Hodgkin lymphoma in young adults, but the risk of NHL goes up as people get older.
  • Melanoma melanoma is one of the most common cancers in people younger than 30
  • Sarcomas (cancers of connective tissues like muscles and bones) There are 2 main types of sarcoma: Soft tissue sarcomas (which start in muscles, fat, blood vessels or other some body tissues), Bone sarcomas
  • Cercix and ovary cancers: Most often it is found in women younger than 50. It rarely occurs in women younger than 20. Ovarian cancer is much more common in older women than in women younger than 40.
  • Thyroid cancer: The risk of thyroid cancer tends to go up as people get older, but it’s often found at a younger age than most other adult cancers. It’s much more common in women than in men.
  • Testicular cancer: Testicular cancer most often develops in younger men. About half of testicular cancers occur in men between the ages of 20 and 34, but it can occur at any age
  • Colorectal cancer: Cancers of the colon and rectum are much more common in older adults, but they can occur at any age. In young adults, they are more likely to be linked to an inherited genetic condition that puts the person at higher risk
  • Leukemia: Leukemias are cancers of the bone marrow and blood. They are the most common cancers in children, but they can occur at any age, and, in fact, most leukemias occur in older adults.
  • Brain and spinal cord tumors:  In children, most brain tumors start in the lower parts of the brain, such as the cerebellum (which coordinates movement) or brain stem (which connects the brain to the spinal cord). Adults are more likely to develop tumors in upper parts of the brain.  Spinal cord tumors are less common than brain tumors in all age groups.

Old Theories about Cancer

Humoral theory

According to Hippocrates there are four different body fluids; which are blood, phlegm, yellow bile and black bile. The balance between these fluids keep the body healthy. 

Lymph theory

Cancer is formed by lymph fluid. Life was believed to consist of continuous movement of the fluids like as blood and lymph in the body. Leukemia is one of the reasons of this theory.

Blastema theory

All cells including cancer cells were derived from other cells.

Chronic irritation theory

Chronic irritation was the cause of cancer. Later Thiersch was showed that cancers metastasize through the spread of malignant cells and not through some unidentified fluid.

Trauma theory

Cancer is caused by trauma.

Parasite theory

Cancer is contagious and spreads through parasite.

Cancer Treatment Methods

Surgery

Surgery is a method that is used since ancient times. However, in 19th century a surgeon noticed that cancer cells were spread from primary tumor to other places through the blood stream (metastasis). Understanding the mechanism(s) of cancer spreading became a key element in recognizing the limitations of cancer surgery. Sonography, computed tomography(CT scans), magnetic resonance imaging (MRI scans) and positron emission tomography (PET scans) have replaced most exploratory operations. Recently, liquid nitrogen spray to freeze and kill cancer cells (cryosurgery) and lasers also used to cut the tumor tissue.

Chemotherapy

Surgeons developed new methods for cancer treatment by combining surgery with chemotherapy and/or radiation. Over the years, use of many chemotherapy drugs has resulted in the successful treatment of many
types of cancers.

New approaches are being studied to reduce the side effects of chemotherapy including use of,

(a) new combinations of drugs,
(b) liposomal and monoclonal antibody therapy to target specifically cancer cells,
(c) chemoprotective agents to reduce chemotherapy side effects,
(d) hematopoietic stem cell transplantation
(e) agents that overcome multidrug resistance.

Hormonal therapy

It is founded by Thomas Beatson in 1878 by his discovery that the breasts of rabbits stopped producing milk after he removed ovaries. Now new classes of drugs (aromatase inhibitors, LHRH analogs) are being used to treat prostate and breast cancers. How hormones influence growth of cancer has guided progress in developing as well as reducing the risk of breast and prostate cancers.

Radiation therapy

Roentgen discovered “X-ray” and after 3 years later radiation was used for cancer diagnosis and in treatment. In the early 20th century, researchers discovered that radiation could cause cancer as well as cure it. 

Several radiation therapies are being used, these include: (a) conformal proton beam therapy (proton beam will be used for killing tumor cells instead of X-rays); (b) stereotactic surgery and stereotactic therapy (gamma knife can be used to deliver and treat common brain tumor); (c) intra-operative radiation therapy (cancer has been removed surgically followed by radiation to the adjacent tissues)

Adjuvant therapy

It is the use of chemotherapy after surgery to destroy the few remaining cancer cells in the body. Adjuvant therapy was used in colon and testis cancers.

Immunotherapy

Use of biological agents that mimic some of the natural signals that body uses to control tumor growth is called immunotherapy. n 1990s scientists produced therapeutic monoclonal antibodies rituximab and trastuzumab that specifically targeted lymphoma and breast cancer cells. 

Targeted Cancer Treatments

Growth signal inhibitors

Scientists recognized that changes in growth factors signaling leads to abnormal behavior of cancer cells. Present targeted therapies that block growth factor signals are trastuzumab, gefitinib, imatinib and cetuximab.

Drugs that induce apoptosis

Apoptosis is a natural process through which cellular DNA gets damaged and cells ultimately will die where as apoptosis induced drugs can force cancer cells to die without DNA repair.

Endogenous angioinhibitors

Angiogenesis is the formation of new blood vessels from existing vessel. Normally angiogenesis is a healthy process, that help the body to heal wounds and repair damaged body tissues, whereas in cancerous condition this process supports new blood vessel formation that provide a tumor with its own blood supply, nutrients and allow it to grow. Angioinhibition is a form of targeted therapy that uses drugs to stop tumors from making new blood vessels. 

There are two general categories of angioinhibitors: (i) antibodies or small molecules that target pro-angiogenic factors of tumor cells such as VEGF, bFGF or PDGF, and (ii) endogenous angioinhibitors such as thrombopondin-1, angiostatin, interferons, endostatin, arresten, canstatin and tumstatin that inhibit angiogenesis by targeting vascular endothelial cells.

Future Cancer Treatments

Antiangiogenic chemotherapy

Angioinhibitors were also being used in combination with conventional chemotherapy. Clinical trails generally combine very low-dose of chemotherapy followed by angioinhibitor therapy. Combination of angioinhibitors will need to be tested vigorously in the future, as single angioinhibitors are approved for use of cancer. Angioinhibitory therapy is generally less toxic and less susceptible to induction of acquired drug resistance.

Ps:  Angiogenesis inhibits the growth of new blood vessels.

More targeted treatments

Antisense oligodeoxynucleotides and small interfering RNA(siRNA) are recently developed molecules that can be used for treatment of cancer.

Nanotechnology

Extremely tiny particles can be used for diagnostic imaging to more accurate location of tumors for delivering drugs more specifically and effectively into cancer cells.

RNA expression profiling and proteomics 

Knowing what proteins or RNA molecules are present by RNA expression profiling in cancer cell can tell about how a cell is behaving and often can help to predict which drugs that particular tumor cell is likely to respond.

Yazan: Kübra Koçdemir

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