The document outlines the six hallmarks of cancer, which are critical biological capabilities that tumors acquire to grow and metastasize: self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis. It summarizes the conceptual progress made in understanding these hallmarks since their introduction in 2000, detailing each hallmark and its mechanisms. Additional hallmarks, such as deregulated metabolism and evasion of the immune system, are briefly mentioned as emerging areas of research.

1. THE
HALLMARKS
OF CANCER
A project submitted in fulfillment of the
requirements for Value Added Course :
Cancer Awareness and Therapy.

2. Introduction
The hallmarks of cancer comprise six
biological capabilities acquired during
the multistep development of human
tumors. The hallmarks constitute an
organizing principle for rationalizing
the complexities of neoplastic disease.
1. Self-Sufficiency in Growth Signals
2. Insensitivity to Anti-Growth Signals
3. Tissue Invasion and Metastasis
4. Limitless Replicative Potential
5. Sustained Angiogenesis (Blood
Vessel Growth)
6. Evasion of Apoptosis (Cell Death)

3. Hallmark
Capabilitie
s —
Conceptual
Progress
The six hallmarks of cancer—distinctive
and complementary capabilities that
enable tumor growth and metastatic
dissemination—continue to provide a solid
foundation for understanding the biology
of cancerIn the first section of this Review,
we summarize the essence of each
hallmark as described in the original
presentation in 2000, followed by selected
illustrations (demarcated by subheadings
in italics) of the conceptual progress made
over the past decade in understanding
their mechanistic underpinnings.

5. Summary of Hallmarks of Cancer
Click to add text
Capability Simple analogy
Self-Sufficiency in Growth Signals "Accelerator pedal stuck on"
Insensitivity to Anti-Growth Signals "Brakes don't work"
Evading Apoptosis
Won't die when the body normally
would kill the defective cell
Limitless Replicative Potential Infinite generations of descendants
Sustained Angiogenesis
Telling the body to give it a blood
supply
Tissue Invasion and Metastasis
Migrating and spreading to other
organs and tissues

6. The Cell Cycle
Clock
Cells do not divide in G0 and are quiescent. After
receiving growth factor signals, they prepare for division
by entering G1, where everything within the cell except
DNA is doubled. This doubling includes the size of the
cell. The next phase of the cell cycle is S (synthesis)
phase. It is the cell cycle phase where the chromosomes
(DNA) are duplicated in preparation for cellular division.

8. Self-Sufficiency in Growth
Signals
Cancer cells do not need stimulation from external signals (in the form
of growth factors) to multiply. Typically, cells of the body require hormones
and other molecules that act as signals for them to grow and divide. Cancer
cells, however, have the ability to grow without these external signals.
There are multiple ways in which cancer cells can do this: by producing
these signals themselves, known as autocrine signalling; by permanently
activating the signalling pathways that respond to these signals; or by
destroying 'off switches' that prevents excessive growth from these signals
(negative feedback). In addition, cell division in normal, non-cancerous cells
is tightly controlled.

10. Insensitivity to Anti-Growth Signals
Cancer cells are generally resistant to growth-preventing signals
from their neighbours. To tightly control cell division, cells have
processes within them that prevent cell growth and division. These
processes are orchestrated by proteins known as tumor suppressor
genes. These genes take information from the cell to ensure that it is
ready to divide, and will halt division if not (when the DNA is
damaged, for example). In cancer, these tumour suppressor proteins
are altered so that they don't effectively prevent cell division, even
when the cell has severe abnormalities.

12. Evading Programmed Cell Death
Apoptosis is a form of programmed cell death (cell suicide), the
mechanism by which cells are programmed to die in the event they
become damaged. Cancer cells are characteristically able to bypass this
mechanism. Cells have the ability to 'self-destruct'; a process known
as apoptosis. This is required for organisms to grow and develop
properly, for maintaining tissues of the body, and is also initiated when a
cell is damaged or infected. Cancer cells, however, lose this ability; even
though cells may become grossly abnormal, they do not undergo
apoptosis.

14. Limitless Replicative Potential
Non-cancer cells die after a certain number of divisions. Cancer cells
escape this limit and are apparently capable of indefinite growth and
division (immortality). But those immortal cells have damaged
chromosomes, which can become cancerous. Cells of the body don't
normally have the ability to divide indefinitely. They have a limited number
of divisions before the cells become unable to divide (senescence), or die
(crisis). The cause of these barriers is primarily due to the DNA at the end
of chromosomes, known as telomeres. Telomeric DNA shortens with every
cell division, until it becomes so short it activates senescence, so the cell
stops dividing.

16. Sustained Angiogenesis
Angiogenesis is the process by which new blood vessels are
formed. Cancer cells appear to be able to kickstart this process,
ensuring that such cells receive a continual supply of oxygen and
other nutrients. Normal tissues of the body have blood vessels
running through them that deliver oxygen from the lungs. Cells must
be close to the blood vessels to get enough oxygen for them to
survive. New blood vessels are formed during the development of
embryos, during wound repair and during the female reproductive
cycle.

18. 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. One of the most well known properties of cancer
cells is their ability to invade neighboring tissues. It is what
dictates whether the tumor is benign or malignant, and is the
property which enables their dissemination around the
body. They then have to invade blood vessels, survive in the
harsh environment of the circulatory system, exit this system

20. Emerging Hallmarks
Deregulated Metabolism: Most cancer cells use alternative metabolic
pathways to generate energy, a fact appreciated since the early
twentieth century with the postulation of the Warburg hypothesis, but
only now gaining renewed research interest.
Evading the Immune System: Despite cancer cells causing increased
inflammation and angiogenesis, they also appear to be able to avoid
interaction with the body's immune system via a loss of interleukin-33.

21. THANK
YOU
A Presentation by
MOHD AZHAN
Department of Computer
Application (BCA)
Enrollment No.