Introduction
to Cancer /
Malignancy
Zulfan Zazuli
Thanks to a lack of evidence, the history
of cancer is often wrought with debate.
But scientists have now found the oldest
example of human cancer in a 1.7million-year-old bone, National
Geographic reports. Scans of the fossil,
a toe bone from South Africa, revealed a
malignant tumor on the left foot of an
unknown human relative. Researchers
diagnosed the tumor as the aggressive
bone cancer osteosarcoma. Together,
say scientists, these fossils show that
even if the modern world has higher
rates of cancer, the triggers for the
disease are found somewhere within our
evolutionary past.
Epidemiology
The International Agency for Research on Cancer – GLOBOCAN 2022
The Hallmarks of Cancer
Established
Emerging hallmarks+enabling characteristics
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar
4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013. PMID: 21376230.
Carcinogenesis
Genetic alterations
• Oncogenes
• Tumor suppressor genes & DNA
repair genes
Epigenetic alterations
• heritable changes in gene expression
without changes in DNA sequence
• e.g. Hypermethylation of Tumor
Suppressor Gene Promoters
Oncogenes & tumor suppressor genes
Oncogenes & tumor suppressor genes
Growth of cancer cells & the effect of treatments
Pathway of metastases:
● Hematogenous
● Lymphatics
Dual role of immune system:
Mainstay treatments
1.
2.
3.
Surgery
Radiation
Systemic anticancer:
• Chemotherapy
• Targeted therapy (MAB)
• Immunotherapy
Can be given sequentially or
concurrently (in combination)
depending on available evidences on
specific cancer
J Clin Biochem Nutr. 2017
Jan;60(1):33-38. doi:
10.3164/jcbn.16-65. Epub
2016 Dec 17. PMID:
28163380
Timing of systemic therapy
Systemic therapy for solid tumor cancer
Adjuvant
therapy
• To eradicate micrometastatic diasese
following surgery/radiation
• To reduce recurrence rates & prolong
survical
• Target: patients with good prognosis w/ no
clinically detectable disease following
surgery/radiation
Systemic therapy for non-solid cancer
(e.g. hematologic malignancy)
•to eradicate
cancer cells
and achieve
remission
Induction
Consolidation
Neoadjuvant
therapy
•to eradicate
remaining
cells
• Given before surgery/radiation to reduce
tumor burden and destroy micrometastase
Maintenance
Palliative care → control symptoms of incurable cancer
• to prevent
recurring
cancer
Anticancer agents
Chemotherapy
Targeted therapy
Immunotherapy
• Targeting rapidly proliferating
• Small molecules & mAbs
• Boosting natural defense
cells
• Blocking intracellular (small
against tumor cells
• Act at one or more phases of
mollecules) and extracellular
• Cytokines; chimeric antigen
cell cycle
(mAbs) signaling pathways
receptor (CAR) T-cell therapies,
immune checkpoint inhibitors,
therapeutic vaccines
Hormonal therapies:
• Cancers whose growth is affected by gonadal hormonal control
• Hormonal treatments either block or decrease the production of endogenous hormones
Chemotherapeutic agents
• Narrow therapeutic index → balance dosing!
• Chemotherapy administration plan:
chemotherapy regimens (combination) →
chemotherapy protocols (detailed procedures
incl. premedications, supportive therapies)
• Administered in cycles:
• Intervals → give time for the body to recover but still produced acceptable
killing rates
• Length/number of cycles → depends on toxicities and treatment goals (based
on EBM)
Combination of chemotherapeutic agents
• Most of chemotherapy are given as a combination:
agents with different pharmacologic actions
agents with different organ toxicities
agents that are active against the tumor and ideally synergistic when
used together
agents that do not result in significant drug interactions
Selection of anticancer regimen
Cancer
characteristics
~Effectiveness
Patients
characteristics
~Safety
•
Selection of regimen or dosing can be adjusted →
based on BSA, organ function (e.g. kidney),
Presence of
molecular biomarker
characteristics
Performance status
Cancer stages
Comorbidities
Type of cancer
Organ function
toxicities, comorbidities
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