Neoplasia refers to abnormal cell growth. This document discusses the causes, types, characteristics, and molecular basis of cancer. Cancer arises due to genetic and environmental factors and defects in genes regulating the cell cycle, DNA repair, apoptosis, and other cellular processes. The major types of cancer are carcinomas, sarcomas, and other rare types. Cancer is characterized by uncontrolled growth, local invasion, and metastasis. Treatments discussed include chemotherapy, radiation, surgery, and targeted therapies. Common cancers like lung and breast cancer are explained in terms of risks, symptoms, and treatments.

1. Neoplasia and Neoplastic
Diseases
Faraza Javed
M.Phil Pharmacology

2. Neoplasia
Neoplasia is defined as:
" An abnormal mass of tissue, the growth of which
exceeds and is uncoordinated with that of the normal
tissues and persists in the same excessive manner after
cessation of the stimuli that evoked the change."

4.  One in three people in the Western world develop
cancer and one in five die of the disease.
 There are approximately 200 types of cancer, each
with different causes, symptoms and treatments.
 In 2007, 297,991 people were newly diagnosed with
cancer in the UK.
 An individual's risk of developing cancer depends on
many factors, including age, lifestyle and genetic
make-up.

5. Causes of Neoplasia
Neoplasia results due to:
 Genetics
 Environmental Causes

6. Genetics:
 A change in the DNA sequence that can be inherited
from either parent (Inherited) OR
 A change in the DNA sequence in cells other than
sperm or egg (Somatic)

7. Somatic
Inherited
Both
Only 5 –10% of cancer cases have a clear
hereditary component.
Even in those cases where susceptibility is clearly
inherited, somatic changes are required for cancer
to develop.

8. External Causes:
 UV Radiations
 X-Rays
 Tobacco Smoke
 Alcohol
 Fatty Food
 Human Papilloma Virus (HPL)
 Human Immunodeficiency Virus (HIV)

9. Nomenclature
In common medical usage, a neoplasm often is referred
to as a Tumor, and the study of tumors is called
Oncology.
Among tumors, the division of neoplasms into Benign
and Malignant categories is based on a judgment of a
tumor’s potential clinical behaviour.

10. 1. Benign Tumor:
Attaching the suffix-oma to the cell of organ and
derived tissue cell + oma/ cell + morphologic character
+ oma
e.g. adenoma of thyroid, ovarian cyst adenoma.

11. 2. Malignant Tumor:
Malignant tumors are collectively referred to as
Cancers. These are classified as Carcinoma and
Sarcoma.

12. Carcinoma:
Malignant tumors of Epithelial cell origin/ name of
organ and derived tissue/ cell + morphologic feature
+ carcinoma
e.g. adenocarcinoma of thyroid, ovarian cyst
adenocarcinoma.

13. Sarcoma:
Malignant tumors arising in Mesenchymal tissue (other
than epithelial cell) or its derivatives / The name of
organ and derived tissue/ cell + sarcoma
e.g. Angiosarcoma.

15. 3. Teratomas:
Tumors containing mature or immature cells or tissues
representative of more than one germ layer and
sometimes all the three layers.
e.g. Ovarian Teratoma

16. 4. Hamartoma:
Tumor-like malformation composed of a haphazard
arrangement of tissues indigenous to the particular site,
which is totally benign.
e.g. Pulmonary Hamartoma

17. 5. Mixed tumors:
Tumors which derived from one germ layer may
undergo divergent differentiation (involve more than 1
type of tissue) creating so called mixed tumor.
e.g. Mixed tumor of salivary gland and Parotid gland.

19. Characteristics of Neoplasm
There are four fundamental features by which benign
and malignant tumors can be distinguished:
 Differentiation and Anaplasia
 Rate of growth
 Local invasion
 Metastasis

20. Differentiation And Anaplasia
Differentiation- Extent to which neoplastic cell
resemble normal cell.
Anaplasia- Lack/ Loss of (structural and functional)
Differentiation of normal cell.
Dysplasia- Disordered Growth. Loss in the uniformity
of individual cell and their architectural orientation.
 It represents a state b/w hyperplasia and carcinoma.
 Does not necessarily progress to cancer.

21.  Benign tumors resemble the tissue of origin and are
well differentiated.
 Malignant tumors are poorly or completely
undifferentiated (anaplstic).

23. Rate of Growth
 Benign tumors are slow growing, whereas malignant
tumors generally grow faster.

24. Local Invasion
 A Benign neoplasm remains localized at its site of
origin. It does not have the capacity to infiltrate,
invade or metastasize to distant site. Most of tumor
develop an enclosing fibrous capsule that separates
them from the host tissue.

25.  Cancer grow by progressive infiltration, invasion
and penetration of surrounding tissue. They do not
develop well defined capsule.
 Next to the development of metastases, local
invasiveness is the most reliable feature that
distinguishes malignant from benign tumor.

27. Metastasis
Metastasis are secondary implants discontinuous with
the primary tumor and located in remote tissues.
 Benign tumor remain localized to the site of origin,
whereas malignant tumor locally invasive and
metastasize to distant site.

29. Molecular Basis of Cancer

30. Cell Cycle
The process of replicating DNA and dividing a cell can
be described as a series of coordinated events that
compose a “cell division cycle.’’
A set of checkpoints that monitor completion of
critical events, leading to cell division and
duplication that produce two daughter cells.

31. 1st type of cell cycle regulation, checkpoint control, is
more supervisory. Cell cycle checkpoints sense flaws in
critical events such as DNA replication and
chromosome segregation. When checkpoints are
activated, for example by underreplicated or damaged
DNA, signals are relayed to the cell cycle-progression
machinery. These signals cause a delay in cycle
progression, until the danger of mutation has been
averted.

34. 2nd is the cascade of protein phosphorylations that relay
a cell from one stage to the next. Cyclin-dependent
kinases (CDKs) are a family of protein kinases
discovered for their role in regulating the cell cycle.
They are also involved in regulating transcription,
mRNA processing, and the differentiation of cells.
CDK binds a regulatory protein called a cyclin, form
cyclin-CDK complex and phosphorylate their respective
substrate and regulate cell cycle.

35. Receptors Protein Function
CDK1 Cyclin A Regulate all cell cycle
stages
Cyclin B M phase
CDK2 Cyclin A All cell stages, G2 phase
Cyclin E S phase
Cyclin D G1 phase

37.  Regulatory phosphorylation and dephosphorylation
fine-tune the activity of CDK–cyclin complexes,
ensuring well-delineated transitions between cell
cycle stages.
 Mutation or deregulation of this process has been
associated with many types of cancers i.e.
uncontrolled cell proliferation. Hence, CDKs are
considered as a potential target for anti-cancer
medication.

38. Molecular Basis of Cancer
Carcinogenesis is a multistep process resulting from the
accumulation of multiple genetic alterations that collectively
give rise to the transformed phenotype.
 DNA Repair Gene
 Oncogenes
 Tumor Suppressor Gene
 Genes Regulating Apoptosis

39. DNA Repair Gene
 DNA repair genes code for proteins whose normal
function is to correct errors that arise when cells
duplicate their DNA prior to cell division.
 DNA repair genes are active throughout the cell
cycle, particularly during G2 after DNA replication
and before the chromosomes divide.

40.  Mutations in DNA repair genes can lead to a failure
in repair, which in turn allows subsequent mutations
to accumulate.
 If the rate of DNA damage exceeds the capacity of
the cell to repair it, the accumulation of errors can
overwhelm the cell and result in cancer.
 A few important DNA repair genes include BRCA1
and BRCA2 gene.

41. Oncogenes
 An oncogene is a proto-oncogene that has been
mutated in a way that leads to signals that cause
uncontrolled growth.
 Oncogenes are "gain of function" genes. They gain
the ability to drive non-stop growth. In spite of their
dominant activities, a single mutated oncogene
usually isn't enough to cause cancer all by itself
because tumor-suppressor genes are acting to put the
brakes on to keep cell growth from getting out of
control.

42.  Oncogenes aren't usually involved in inherited forms
of cancer because most occur as somatic mutations
and can't be passed from parent to child.
 Example of Oncogenes include HER-2, RAS, SRC,
hTERT.

43. Tumor Suppressor Gene
Tumor suppressor genes in normal cells act as braking
signals during phase G1 of the cell cycle, to stop or
slow the cell cycle before S phase. If tumor-suppressor
genes are mutated, the normal brake mechanism will be
disabled, resulting in uncontrolled growth, i.e. cancer.

44.  Mutations in tumor-suppressor genes cause loss-of-
function. Loss-of-function mutations generally
only show up when both copies of the gene are
mutated. In other words, if a pair of tumor
suppressor genes are lost or mutated, their functional
absence might allow cancer to develop.
 Individuals who inherit an increased risk of
developing cancer often are born with one defective
copy of a tumor suppressor gene.

45.  Because genes come in pairs (one inherited from
each parent), an inherited defect in one copy will not
lead to cancer because the other normal copy is still
functional. But if the second copy undergoes
mutation, the person then may develop cancer
because there is no longer any functional copy of the
gene.
 P53, Rb, APC are few examples of tumor suppressor
genes.

46. Genes Regulating Apoptosis
Apoptosis is the death of cells which occurs as a
normal and controlled part of an organism's growth
or development.
Mutations of these genes that regulate apoptosis result
in evasion of Apoptosis, would also be a factor in
carcinogenesis.
Genes involve in regulation of Apoptosis include BCL2,
p53 and MYC.

47. Hall Marks of Cancer
Each cancer gene has a specific function, the
dysregulation of which contributes to the origin or
progression of malignancy. It is best, therefore, to
consider cancer related genes in the context of several
fundamental changes in cell physiology, the so­called
hallmarks of cancer, which together dictate the
malignant phenotype.

49. Self-Sufficiency of Growth Signals
Normal cells require external growth signals (growth
factors) to grow and divide. These signals are
transmitted through receptors that pass through the cell
membrane. When the growth signals are absent, cell
stop growing.
Cancer cells do not need stimulation from external
signals (in the form of growth factors) to multiply.
Cancer cells can grow and divide without external
growth signals.

50. The best documented examples of over expression involve the
epidermal growth factor (EGF) receptor family. These signaling
proteins couple growth factor receptors to their nuclear targets.
They receive signals from activated growth factor receptors
and transmit them to the nucleus, either through second
messengers or through a cascade of phosphorylation and activation
of signal transduction molecules.

51. Two important members in this category are RAS and
ABL.
RAS is a member of a family of small G proteins that
bind [GTP] and [GDP], similar to the
larger trimolecular G proteins. Due to mutation RAS is
locked into its active GTP form and the cell is forced
into a continuous proliferating state.

52.  Activated ras then causes the activation of a cellular
kinase called RAF­1. RAF­1 kinase then
phosphorylates another cellular kinase called MEK.
This cause the activation of MEK. Activated MEK
then phosphorylates another protein kinase called
MAPK causing its activation i.e MAP Kinase Pathway
and ultimately causes changes in gene transcription.
 RAF and MEK are targeted sites for anti cancer drugs.

54. Insensitivity to Anti-Growth Signal
The growth of normal cells is kept under control by
growth inhibitors in the surrounding environment, in the
extracellular matrix and on the surfaces of neighboring
cells. These inhibitors act on the cell cycle clock, by
interrupting cell division in the interphase.
Cancer cells are generally resistant to these growth­
preventing signals.

55. Evading Apoptosis
Cells are born, live for
a given period
of time and then die
APOPTOSIS
Physiological cell death
Cell suicide
Cell deletion
Programmed cell death

56. When ligand bind to receptor tyrosine kinase, receptor
get activation and this signaling activates PI3K which
catalyses phosphorylation of inositol phosphates (PIP2
to PIP3). These act as second messengers and recruit
molecules such as Akt kinase to the cell membrane.
AKT Kinase phosphorylate BAD and Forkhead Proteins
that promote cell survival.

57. BAD (Pro­apoptotic Protein) is activated when it is non
phosphorylated and hence cause apoptosis. AKT causes
phosphorylation of BAD that results in antiapoptotic
effect.
Receptor Tyrosine Kinase Inhibitors or more precisely
AKT inhibitors are now developed as an anticancer
agents.

59. Limitless Replicative Potential
 Mammalian cells have an intrinsic program, the
Hayflick Limit, that limits their multiplication to a
certain limit.
 This limit can be overcome by disabling their pRB
and p53 tumor suppressor proteins, which allows
them to continue doubling until they reach a stage
called crisis that results in emergence of an
immortalized cell that can double without limit.

60.  The counting device for cell doublings is the
telomere, which loses DNA at the tips of every
chromosome during each cell cycle. Many cancers
involve the up regulation of telomerase, the enzyme
that maintains telomeres.

61. Sustained Angiogenesis
 Angiogenesis is the growth of blood vessels from the
existing vasculature. It is also a fundamental step in the
transition of tumors from a dormant state to a malignant one.
 Tumors cannot grow beyond a certain size, generally 1–
2 mm3, due to a lack of oxygen and other essential nutrients.
HIF­1(Hypoxia inducible factor) act as a transcription factor
to activate the GF.

62.  To supply nutrients and oxygen, tumors induce
blood vessel growth (angiogenesis) by secreting
various growth factors (e.g. VEGF). Growth factors
such as bFGF and VEGF can induce capillary
growth into the tumor.
 Angiogenesis is involved in the growth of cervix,
breast and melanoma tumors. Anti­VEGF antibodies
slowed the growth of tumors in mice. Anti­
angiogenesis compounds are under investigation as
drugs to treat cancer.

63. Tissue Invasion and Metastasis
Cancer cells can break away from their site or organ of
origin to invade surrounding tissue and spread
(metastasize) to distant body parts.
Normal cell–cell interactions is regulated, through
 Cell–cell adhesion molecules (CAMs)
 Integrins

64. CAM and Integrin becomes altered and results in
metastases as in lung cancer and colorectal cancer and
allow Primary tumor masses spawn "pioneer cells" that
invade adjacent tissues, and may then travel to distant
sites to establish metastases.

65. Neoplastic Diseases

66. Lungs Cancer
 Lung cancer is the number one cancer killer of men
and women.
 Most cases of lung cancer are
related to cigarette smoking.
 Cancer may be caused by a
combination of genetic factors
and exposure to radon gas
or other forms of air pollution
including second­hand smoke.

67. Symptoms
 Persistent Cough
 Blood-streaked Sputum
 Chest Pain
 Fever
 Fatigue
 Wheezing and Shortness of Breath
 Pneumonia

68. Treatment
 Chemotherapy
 Radiotherapy
 Surgery

69. Breast Cancer
Cancer of the breast is the 2nd leading cause of cancer
deaths in women.
Risk factors for developing breast cancer include:
 Obesity
 Alcohol Consumption
 Hormone Replacement Therapy
 Ionizing Radiation and
 Having Children late or not at all

70. Symptoms
 Lump in the breast
 Dimpling of skin
 Skin irritation
 Red Scaly Patch on Skin
 Swollen Lymph Nodes
 Constant Pain in breast and armpit area

71. Treatment
 Lumpectomy
 Radical Mastectomy
 Chemotherapy
 Hormone Blocking Therapy
 Monoclonal Antibodies
 Radiotherapy

72. Colon and Rectal Cancers
 Third most common cancers in men and women but
90% of colorectal cancers are preventable.
 Risk factors: Age over 50 years, obesity, family
history of colon or rectal cancer, diet high in fats and
low in fiber, smoking, high alcohol consumption,
lack of exercise, inflammatory bowel disease and
ulcerative colitis.
 It typically starts as a benign tumor which over time
becomes cancerous.

73. Symptoms
 Nausea and Vomiting
 Change in bowel movements
 Loss of appetite
 Blood in Stool
 Worsening Constipation
 Weight Loss

74. Treatment
 Chemotherapy
 Radiotherapy
 Surgery

75. Skin Cancer
Long-term sun exposure (UV Radiations) can result in
skin cancer. Malignant melanoma is the deadliest form
of skin cancer.
Use the ABCD rule to detect melanoma.
 Asymmetry: Half of a mole does not look like the
other half
 Border irregularity: The edges are uneven
 Color: Pigmentation is not uniform
 Diameter: Larger than a pea

76. Treatment
 Chemotherapy
 Surgery
 Skin Grafting

77. Prostate Cancer
Prostate cancer is the carcinoma of prostate gland that
may spread to other parts of the body particularly bones
and lymph nodes.
Symptoms:
 Weak or interrupted urine flow
 Blood in urine
 Nocturia, Dysuria
 Pain in Pelvis

78. Treatment
 Chemotherapy
 Radiotherapy
 Prostectomy

79. Leukemia
Leukemia is a group of cancers that usually begins in
the bone marrow and results in high number of
abnormal white blood cells. There are 4 main types of
leukemia:
 Acute Lymphoblastic Leukemia (ALL)
 Acute Myeloid Leukemia (AML)
 Chronic Lymphoblastic Leukemia (CLL)
 Chronic Myeloid Leukemia (CML)

80. Symptoms
 Bleeding and Bruising Problems
 Lack of Blood Platelets
 Pinprick Bleeds (Petechiae) on Skin
 Anemia
 Swollen Lymph Nodes
 Weight Loss
 Opportunistic Infections

81. Treatment
 Chemotherapy
 Radiotherapy
 Bone marrow transplantation

82. Cancer’s Seven Warning Signals

83. Awareness Programs
Ribbon Awareness Campaign
You can be a victim of cancer or a survivor of cancer.
It’s a mindset.

84. Hope is the Physician of Each Misery

86. References
 Robbins Basic Pathology, 9th Edition.
 Kopnin, B. P.Targets of oncogenes and tumor suppressors:
key for understanding basic mechanisms of
carcinogenesis. Biokhimiya 65, 2–27 (2000).
 Hahn, W. C. & Weinberg, R. A. Rules for making human
tumor cells. New England Journal of Medicine 347, 1593–
1603.
 Bric, A., Miething, C. et al. Functional identification of
tumor-suppressor genes through an in vivo RNA interference
screen in a mouse lymphoma model.Cancer Cell 16, 324–335
(2009).

87.  Hallmarks of Cancer, Cancer Research UK Science
Update blog, November 2010.
 Lazebnik Y (April 2010). "What are the hallmarks of
cancer?". Nat. Rev. Cancer 10(4): 232–3.
 Hams NL, Jaffa ES, Stein H et al. A revised
European-American classification of lymphoid
neoplasms: A proposal from the International (2010);
84: 1361-92.