This document discusses cancer and its characteristics. It covers topics like the magnitude of cancer around the world, defining prognosis, screening recommendations, cancer syndromes, and phenotypic characteristics of malignant cells. Specifically, it outlines the US Preventive Services Task Force and American Cancer Society screening guidelines. It also lists the key phenotypic characteristics that distinguish cancer cells, including deregulated proliferation, failure to differentiate, genetic instability, evasion of immune surveillance, and more.

1. DR. JUAN CARLOS BECERRA MARTÍNEZ
CÁTEDRA DE MEDICINA INTERNA-MC3087
Tecnológico de Monterrey
Campus Guadalajara

2. The Magnitude of the Problem
Harrison's Principles of Internal Medicine. 18th Ed.

3. The Magnitude of the Problem
Harrison's Principles of Internal Medicine. 18th Ed.

4. The Magnitude of the Problem
Harrison's Principles of Internal Medicine. 18th Ed.

5. The Magnitude of the Problem
Harrison's Principles of Internal Medicine. 18th Ed.

6. The Magnitude of the Problem
Harrison's Principles of Internal Medicine. 18th Ed.

7. The Magnitude of the Problem
Harrison's Principles of Internal Medicine. 18th Ed.

8. Cancer Around the World
Harrison's Principles of Internal Medicine. 18th Ed.

9. Defining the Prognosis
Harrison's Principles of Internal Medicine. 18th Ed.

10. Defining the Prognosis
Harrison's Principles of Internal Medicine. 18th Ed.

11. Tumor Markers
Harrison's Principles of Internal Medicine. 18th Ed.

12. Suspected Carcinogens
Harrison's Principles of Internal Medicine. 18th Ed.

13. Suspected Carcinogens
Harrison's Principles of Internal Medicine. 18th Ed.

14. Screening for Specific Cancers
Harrison's Principles of Internal Medicine. 18th Ed.
 USPSTF (U.S. Preventive Services Task Force)
 "A": The USPSTF strongly recommends that clinicians
provide (the service) to eligible patients; "B": The USPSTF
recommends that clinicians provide (this service) to
eligible patients;
 "C": The USPSTF makes no recommendation for or
against routine provision of (the service);
 "D": The USPSTF recommends against routinely
providing [the service] to asymptomatic patients;
 "I": The USPSTF concludes that the evidence is
insufficient to recommend for or against routinely
providing (the service).
 ACS, American Cancer Society

15. Screening for Specific Cancers
Harrison's Principles of Internal Medicine. 18th Ed.

16. Screening for Specific Cancers
Harrison's Principles of Internal Medicine. 18th Ed.

17. Screening for Specific Cancers
Harrison's Principles of Internal Medicine. 18th Ed.

18. The Clonal Origin and Multistep
Nature of Cancer
Harrison's Principles of Internal Medicine. 18th Ed.

19. The Clonal Origin and Multistep
Nature of Cancer
Harrison's Principles of Internal Medicine. 18th Ed.

20. The Clonal Origin and Multistep
Nature of Cancer
Harrison's Principles of Internal Medicine. 18th Ed.

21. The Clonal Origin and Multistep
Nature of Cancer
Harrison's Principles of Internal Medicine. 18th Ed.

22. The Clonal Origin and Multistep
Nature of Cancer
Harrison's Principles of Internal Medicine. 18th Ed.

23. The Clonal Origin and Multistep
Nature of Cancer
Harrison's Principles of Internal Medicine. 18th Ed.

24. Familial Cancer Syndromes
Harrison's Principles of Internal Medicine. 18th Ed.

25. Familial Cancer Syndromes
Harrison's Principles of Internal Medicine. 18th Ed.

26. Phenotypic Characteristics of
Malignant Cells
Harrison's Principles of Internal Medicine. 18th Ed.
 Deregulated cell proliferation:
 Loss of function of negative growth regulators
(suppressor oncogenes, i.e., Rb, p53), and
increased action of positive growth regulators
(oncogenes, i.e., Ras, Myc). Leads to aberrant
cell cycle control and includes loss of normal
checkpoint responses.

27. Phenotypic Characteristics of
Malignant Cells
Harrison's Principles of Internal Medicine. 18th Ed.
 Failure to differentiate:
 Arrest at a stage before terminal differentiation.
May retain stem cell properties. (Frequently
observed in leukemias due to transcriptional
repression of developmental programs by the
gene products of chromosomal translocations.)

28. Phenotypic Characteristics of
Malignant Cells
Harrison's Principles of Internal Medicine. 18th Ed.
 Loss of normal apoptosis pathways:
 Inactivation of p53, increases in Bcl-2 family
members. This defect enhances the survival of
cells with oncogenic mutations and genetic
instability and allows clonal expansion and
diversification within the tumor without activation
of physiologic cell death pathways.

29. Phenotypic Characteristics of
Malignant Cells
Harrison's Principles of Internal Medicine. 18th Ed.
 Genetic instability:
 Defects in DNA repair pathways leading to either
single or oligo-nucleotide mutations (as in
microsatellite instability, MIN) or more commonly
chromosomal instability (CIN) leading to
aneuploidy. Caused by loss of function of p53,
BRCA1/2, mismatch repair genes, DNA repair
enzymes, and the spindle checkpoint.

30. Phenotypic Characteristics of
Malignant Cells
Harrison's Principles of Internal Medicine. 18th Ed.
 Loss of replicative senescence:
 Normal cells stop dividing in vitro after 25–50
population doublings. Arrest is mediated by the
Rb, p16INK4a, and p53 pathways. Further
replication leads to telomere loss, with crisis.
Surviving cells often harbor gross chromosomal
abnormalities. Relevance to human in vivo
cancer remains uncertain. Many human cancers
express telomerase.

31. Phenotypic Characteristics of
Malignant Cells
Harrison's Principles of Internal Medicine. 18th Ed.
 Increased angiogenesis:
 Due to increased gene expression of
proangiogenic factors (VEGF, FGF, IL-8) by
tumor or stromal cells, or loss of negative
regulators (endostatin, tumstatin,
thrombospondin).

32. Phenotypic Characteristics of
Malignant Cells
Harrison's Principles of Internal Medicine. 18th Ed.
 Invasion:
 Loss of cell-cell contacts (gap junctions,
cadherins) and increased production of matrix
metalloproteinases (MMPs). Often takes the form
of epithelial-to-mesenchymal transition (EMT),
with anchored epithelial cells becoming more like
motile fibroblasts.

33. Phenotypic Characteristics of
Malignant Cells
Harrison's Principles of Internal Medicine. 18th Ed.
 Metastasis:
 Spread of tumor cells to lymph nodes or distant
tissue sites. Limited by the ability of tumor cells
to survive in a foreign environment.

34. Phenotypic Characteristics of
Malignant Cells
Harrison's Principles of Internal Medicine. 18th Ed.
 Evasion of the immune system:
 Downregulation of MHC class I and II molecules;
induction of T cell tolerance; inhibition of normal
dendritic cell and/or T cell function; antigenic loss
variants and clonal heterogeneity; increase in
regulatory T cells.