A detailed summary of chapter 9 (METASTASIS) from the course literature: Molecular biology of cancer, Pecorino, 5th edition (ISBN-9780198833024) for 'Oncology' (AB_1184).
Metastasis: Occurs when cancer cells spread from the primary tumour to other parts of the
body, often before initial diagnosis. This can result in the detection of secondary tumours
during the early stages of cancer diagnosis.
Adjuvant therapy is additional treatment that is given after the primary treatment
(usually surgery) to lower the risk of cancer returning (e.g., chemotherapy, radiotherapy,
targeted therapy, immunotherapy). However, its effectiveness varies; it may not always
prevent recurrence, particularly in cases where metastases are already present or where
the cancer is highly aggressive.
The spread of cancer cells can be lethal
Physical obstruction: Metastatic cancer cells can form large masses that physically obstruct
the normal function of organs and tissues. This can block vital pathways (e.g., airways,
blood vessels, GI tract), leading to critical issues like breathing difficulties, impaired blood
flow, and digestive problems.
Cancer cells compete aggressively with normal cells for nutrients and oxygen. Since
cancer cells often have a higher metabolic rate, they can outcompete normal cells, and
deprive them of the resources needed for survival and proper function. This competition
can weaken normal cells and impair organ function.
, Both physical obstruction and resource competition lead to the interference with the
normal functioning of organs. As cancer cells spread and invade organs, they disrupt the
balance of cellular activities, leading to organ failure. Example: Metastases in the liver can
impair detoxification processes, while in the lungs, they can reduce oxygen exchange, and
in the brain, they can disrupt neurological functions. This systemic failure of critical organs
is a primary cause of death in cancer patients.
Organotropism of metastases
Organotropism refers to the tendency of metastatic cancer cells to spread to specific
organs. This phenomenon can be explained by the directionality of blood flow, which
influences where circulating cancer cells are likely to settle and form secondary tumours.
Example: gastrointestinal cancers often
metastasize to the liver because blood
from the GI tract flows directly to the liver
via the portal vein.
Seed and soil hypothesis
Paget: “The seeds of a plant are carried
in all directions; but they can only live and
grow if they fall on congenial soil”
This hypothesis explains that metastasis depends on the compatibility between
cancer cells and the environment of the target organ. A pre-established niche means
certain organs are naturally more conducive to cancer cell growth due to their
microenvironment. Pre-metastatic niche formation involves the primary tumour preparing
distant sites to support metastasis by modifying the local environment.
Pre-established niche
Certain organs inherently provide a favourable
microenvironment for cancer cells, including
factors like blood supply, immune cell presence,
and specific growth factors that make the organ
conducive to tumour cell colonization and
proliferation.
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