Cancer: Intro, Types, Development and Therapy

Cancer: Intro, Types, Development and Therapy

Introduction

  • Cancer is a loss of cell cycle regulation that cause excessive cell division in uncontrolled manner.
  • Cancer is caused by various type of tumour promoting chemical, hormones, viruses, bacteria, and xenobiotic called carcinogens.
  • A normal cell undergoes controlled division, differentiation and apoptosis i.e. programmed cell death but when normal cell have lost the usual control over their division, differentiation and apoptosis they become cancer causing tumour cells.
  • Two heritable properties which defined the cancer cells:
    • They reproduce or divide defiance of the normal restraints on cell growth and division.
    • They colonize and invade territories normally reserved for other cells.
  • It is the combination of these properties that makes cancers particularly dangerous.
  • The process by which normal cell converted into cancer cell is known as transformation and the cell is termed as transformed cell.
  • It is the combination of these properties that makes cancers particularly dangerous.
  • The process by which normal cell converted into cancer cell is known as transformation and the cell is termed as transformed cell.
  • On the basis of dispersal properties cancer is of two types:
    • Benign tumour: It is abnormal increase in mass and proliferation of somatic tissue. In benign cells CAM & ECM genes are upregulated and cells are tightly held with each other and form compact mass. Treatment of benign tumour is easy by drug base treatment and surgery.
    • Malignant tumour: It is later stage of Cancer development in which cancer cell acquired ability to invade in the surrounding tissue. Invasiveness is the main property of cancer in which allowed to movement of Cancer cell from the origin to other body parts by blood and lymph and form secondary tumour and process is called metastasis.

Comparison of benign and malignant Tumour

Benign tumour Malignant tumour
Slow rate of growth Fast rate of growth
Well differentiated Lacks differentiation
Non-invasiveness Invasive to other organ
No spreading Spreading
Metastasis absent Metastasis present
Capsulated Non-capsulated

Benign and malignant tumor

Important feature of Cancer cell

  • Loss of apoptosis.
  • Limitless replicating potential.
  • Excess growth of blood vessel.
  • Insensitivity to anti-growth factor.
  • Self sufficiency in growth signal.
  • Growth receptors are over expressed and death receptors are mutated.
  • No contact dependent inhibition.
  • Cancerous cells show clonal origin.

Classification of cancer on the basis of origin

Tissue of origin Tumour
White blood cell Leukaemia
Lymphocytes Lymphoma
Epithelial Carcinoma
Nerve cell Neuroblastoma
Blood vessel Lymphosarcoma
Glial cell Glioblastoma
Bone Osteosarcoma

Four main genes related with cancer development

  • Proto-oncogene- gain of functions leads cancer.
  • Tumour suppressor gene- loss of function cause cancer.
  • Care taker gene- loss of function cause cancer.
  • Apoptotic gene- loss of function in pro-apoptotic gene and gain of function in anti-apoptotic gene leads to cancer.

Genes involved in cancer development and their examples

Proto-oncogenes

  • Normally this cell promotes cell survival and function.
  • Examples of gene product are anti- apoptotic proteins, Signalling components and signal transduction pathways which results in proliferation, transcription factor.
  • Gain of function in these cells results in unregulated cell proliferation and survival and mutation involved are generally dominant type which arises due point mutation, amplification and chromosomal aberrations.
  • Types of Proto-oncogene:
    • Sis- encodes PDGF.
    • abl- encodes Tyrosine kinases.
    • Jun-Fos- acts as transcription factor.
    • Erb-A- acts as Thyroxin hormone receptor.

Tumour suppressor gene

  • They are mainly responsible for inhibition of cell survival and proliferation, and apoptosis – promoting proteins, cell cycle progression inhibitors, checkpoint pathways proteins that restrains or controls the proliferation.
  • Unregulated cell proliferation and survival are resulted due to loss of function mutation in tumour suppressor genes and mutation are generally recessive which are arises due to methylation, point mutation and deletion.
  • Examples:
    • P53 and P21 Maintain the integrity of genome and it is mutated in all types of cancer.
    • Retinoblastoma (Rb)-  It is important cell cycle regulator and inhibits the activity of transcription factor E2F which is essential for G1 to S phase transition.

Caretaker genes

  • It normally protect the integrity of genome that means it involves in DNA repair mechanism.
  • If care taker genes are mutated or loss of function mutation which allows to accumulate and mutation are recessive type occurs because of methylation, point mutation and deletion.
  • Examples:
    • ATM & ATR- It is sensor protein, it sense DNA strand break if it is mutated then cause cancer development.

Apoptotic gene

  • It is most important gene which involves in the regular of cellular life.
  • It is of two types:
    • Anti-apoptotic gene- Normally it involves in prevention of apoptosis but in gain of function mutation, function of these genes is triggered and lifespan is increased, which promotes cancer development.
    • Pro-apoptotic gene- In normal state it promotes apoptosis, but loss of function mutation in these mutation triggered cancer development and cells are immortal.

Carcinogenesis/oncogenesis

  • It is a multi-step process, in which multiple genetic alterations is responsible for transformation of normal cell into cancerous cell.
  • A series of mutation in multiple gene create progressive rapid cell division that escape normal cell growth and create opportunity for additional mutation.
  • At later stage, many clonal cells are grown and come and contact with each other and form primary tumour.
  • Sometime it migrate into another site and form secondary tumour and process is called metastasis.

Carcinogens

  • Carcinogens are those factors that induces cancer development.
  • It may be physical agent like X-ray and UV rays, chemical agents and biological agents.
  • Cancer is very gradual process.
  • Tumour progression involve initially low grade of neoplasticity later high grade of neoplasticity and finally invasive property.
  • Chemical Carcinogens are of two types:
    • Direct Carcinogens- (Primary Carcinogens): It bind with DNA directly and induce cancer development, it is mainly electrophilic in nature and modified nitrogenous base of DNA, examples includes vinyl chloride, EMS, DMS and nitrogen mustard.
    • Indirect Carcinogens- Generally non- reactive and non-carcinogenic in nature but it is modified by cellular enzymes and these molecules converted into highly carcinogenic compound, example includes Aflatoxin.

Carcinogens and their examples

Carcinogens Properties and examples
Physical UV and gamma rays
Chemical Benzopyrene, benzene, arsenic, rodon, cadbium, njctotine
Biological DNA containing- Hepatitis B virus, papilloma virus, herpes virus, RNA containing- HTLV -1 & HTLV -2

Molecular basis of cancer

  • Those genes whose genetic and epigenetic changes involves in the cancer or tumorigenesis and termed as cancer critical genes.
  • It means alterations in all these responsible for cancer and evolution of cancer by causing tumorigenesis.
  • These genes may be involved in the following processes:
    • Cell cycle progression- e.g. RB1, MYC
    • Differentiation process- e.g. APC
    • DNA repair- e.g. ATM, BRCA
    • Cell death- e.g. BCL2.

Cancer Therapy

Different types of approaches used in Cancer treatment:

  • Radiation based therapy: In this therapy radiations are used to destroy cancerous cells but normal cells are also destroyed.
  • Surgery: Applicable only for tumour but cannot be used for metastatic tumour.
  • Chemotherapy: It is most common, drugs used in chemotherapy normally inhibits DNA replication,  gene expression, cell Signalling,  apoptosis,  inhibitors of growth factors and inhibitors of cell cycle Activator.
    • Limitations of chemotherapy are, cancerous cells develop MDR, XDR and TDR strain by amplifying ABC gene.
  • Immunotherapy
    • Passive immunotherapy: Administration of antibody as a therapeutic agent in cancerous patient. These antibody binds with specific protein on cell surface and behave as an antagonist and agonist in nature,
    • E.g. Herceptin (humanized antibody used directly against cell surface growth receptors and triggered receptor internalization and it is used for breast cancer)
    • Erbulix– Used against EGF and inactivate receptor.
    • Avastin– Used against VEGF receptor.
  • Active immunotherapy: In malignant cells some proteins are allowed to over expressed, e.g. inhibitory receptor and activation of NK cells.

Reference and Sources

  • https://en.wikipedia.org/wiki/Invasion_(cancer)
  • https://www.taylorfrancis.com/chapters/mono/10.1201/9781315735368-20/part-cells-social-context-cancerbruce-
    alberts-alexander-johnson-julian-lewis-david-morgan-martin-raff-keith-roberts-peter-walter-johnwilson-
    tim-hunt#:~:text=Cancer cells are defined by two heritable properties:,tissue and cell type from which
    they arise.
  • https://www.sanfoundry.com/life-sciences-questions-answers-cancer/
  • https://www.sciencedirect.com/topics/medicine-and-dentistry/gain-of-function-mutation
  • https://www.ncbi.nlm.nih.gov/books/NBK9963/
  • https://www.healthline.com/health/cancer/tumor-suppressor-genes
  • https://www.sciencedirect.com/topics/neuroscience/carcinogens
  • https://www.toppr.com/guides/biology/difference-between/benign-and-malignant-tumors/
  • https://en.wikipedia.org/wiki/Caretaker_gene
  • https://pubmed.ncbi.nlm.nih.gov/8672863/

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