PHARMACOTHERAPY OF NEOPLASTIC
DISEASES
1. Cell Biology of Cancer
2. Factors Involved in Malignant Transformation
3. Therapeutic Alternatives for the Treatment of Neoplasms
4. Pharmacotherapy: Immunotherapy, Targeted Therapy, Hormonal Therapy and
Chemotherapy
5. Drug Resistance and Combination Strategies
6. Conclusions
Bibliography
Goodman & Gilman's The Pharmacological Basis of Therapeutics
Human Pharmacology, Jesús Flórez, 6th edition
Harrison's Principles of Internal Medicine, 18th edition
Introduction
Cancer is not a single disease but a collection of disorders that can arise in virtually
any tissue. It encompasses carcinomas (epithelial origin), sarcomas (connective
tissue), gliomas (glial cells), leukaemias and lymphomas (haematopoietic system),
among others. Although they share fundamental biological hallmarks – sustained
proliferation, evasion of growth suppressors, resistance to cell death, replicative
immortality, induction of angiogenesis, and activation of invasion and metastasis –
the molecular drivers and clinical behaviour differ profoundly. Modern oncological
pharmacotherapy has evolved from classical cytotoxic chemotherapy to a
sophisticated arsenal that includes targeted therapies, immunotherapy, hormonal
agents and, increasingly, personalised medicine guided by tumour genomics. This
lecture provides a comprehensive overview of the pharmacological principles and
therapeutic modalities used to treat neoplastic diseases.
, 1. Cell Biology of Cancer
Cancer originates from a single cell that has accumulated multiple genetic and
epigenetic alterations, leading to uncontrolled proliferation and the ability to
colonise distant organs. The transformation from a normal cell to a malignant one
is a multistep process classically divided into initiation, promotion and progression.
During initiation, a permanent DNA alteration (mutation) occurs in genes that
control cell growth and survival. These mutations can be caused by carcinogens
(chemicals, radiation, viruses) or arise spontaneously. Promotion involves clonal
expansion of the initiated cell, often driven by factors that stimulate proliferation
(e.g., hormones, chronic inflammation). Progression is characterised by the
accumulation of further mutations, genetic instability and the acquisition of
invasive and metastatic capabilities.
Tumour cells are not a homogeneous population; they display considerable genetic
and phenotypic heterogeneity. Only a subset, known as cancer stem cells, may
possess the ability to self-renew and sustain tumour growth. The capacity to
metastasise depends on interactions between tumour cells and the
microenvironment, including signals from the extracellular matrix, immune cells,
and specific organ niches (the “seed and soil” hypothesis).
The cell cycle is the engine of proliferation. It is divided into four active phases (G1,
S, G2, M) and a quiescent state (G0). Progression through the cycle is governed by
cyclins, cyclin-dependent kinases (CDKs) and checkpoint proteins (e.g., p53, Rb). In
cancer, these controls are disrupted, allowing unscheduled division and genomic
instability.
2. Factors Involved in Malignant Transformation
2.1 Oncogenes and Tumour Suppressor Genes
Oncogenes are mutated or overexpressed versions of proto-oncogenes. Their
protein products drive cell proliferation, inhibit apoptosis, or both. Activation
mechanisms include point mutations (e.g., RAS), gene amplification
(e.g., *HER2/neu*, MYC), and chromosomal translocations (e.g., BCR-ABL in chronic
myeloid leukaemia). Oncogenes are dominant: mutation in a single allele can
promote transformation.
DISEASES
1. Cell Biology of Cancer
2. Factors Involved in Malignant Transformation
3. Therapeutic Alternatives for the Treatment of Neoplasms
4. Pharmacotherapy: Immunotherapy, Targeted Therapy, Hormonal Therapy and
Chemotherapy
5. Drug Resistance and Combination Strategies
6. Conclusions
Bibliography
Goodman & Gilman's The Pharmacological Basis of Therapeutics
Human Pharmacology, Jesús Flórez, 6th edition
Harrison's Principles of Internal Medicine, 18th edition
Introduction
Cancer is not a single disease but a collection of disorders that can arise in virtually
any tissue. It encompasses carcinomas (epithelial origin), sarcomas (connective
tissue), gliomas (glial cells), leukaemias and lymphomas (haematopoietic system),
among others. Although they share fundamental biological hallmarks – sustained
proliferation, evasion of growth suppressors, resistance to cell death, replicative
immortality, induction of angiogenesis, and activation of invasion and metastasis –
the molecular drivers and clinical behaviour differ profoundly. Modern oncological
pharmacotherapy has evolved from classical cytotoxic chemotherapy to a
sophisticated arsenal that includes targeted therapies, immunotherapy, hormonal
agents and, increasingly, personalised medicine guided by tumour genomics. This
lecture provides a comprehensive overview of the pharmacological principles and
therapeutic modalities used to treat neoplastic diseases.
, 1. Cell Biology of Cancer
Cancer originates from a single cell that has accumulated multiple genetic and
epigenetic alterations, leading to uncontrolled proliferation and the ability to
colonise distant organs. The transformation from a normal cell to a malignant one
is a multistep process classically divided into initiation, promotion and progression.
During initiation, a permanent DNA alteration (mutation) occurs in genes that
control cell growth and survival. These mutations can be caused by carcinogens
(chemicals, radiation, viruses) or arise spontaneously. Promotion involves clonal
expansion of the initiated cell, often driven by factors that stimulate proliferation
(e.g., hormones, chronic inflammation). Progression is characterised by the
accumulation of further mutations, genetic instability and the acquisition of
invasive and metastatic capabilities.
Tumour cells are not a homogeneous population; they display considerable genetic
and phenotypic heterogeneity. Only a subset, known as cancer stem cells, may
possess the ability to self-renew and sustain tumour growth. The capacity to
metastasise depends on interactions between tumour cells and the
microenvironment, including signals from the extracellular matrix, immune cells,
and specific organ niches (the “seed and soil” hypothesis).
The cell cycle is the engine of proliferation. It is divided into four active phases (G1,
S, G2, M) and a quiescent state (G0). Progression through the cycle is governed by
cyclins, cyclin-dependent kinases (CDKs) and checkpoint proteins (e.g., p53, Rb). In
cancer, these controls are disrupted, allowing unscheduled division and genomic
instability.
2. Factors Involved in Malignant Transformation
2.1 Oncogenes and Tumour Suppressor Genes
Oncogenes are mutated or overexpressed versions of proto-oncogenes. Their
protein products drive cell proliferation, inhibit apoptosis, or both. Activation
mechanisms include point mutations (e.g., RAS), gene amplification
(e.g., *HER2/neu*, MYC), and chromosomal translocations (e.g., BCR-ABL in chronic
myeloid leukaemia). Oncogenes are dominant: mutation in a single allele can
promote transformation.
