Untitled Quiz

Molecular Basis of Cancer

• Cancer is characterized by specific hallmarks, including uncontrolled cell growth, insensitivity to growth inhibitors, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, ability to invade and metastasize, evasion of immune surveillance, and defects in DNA repair.
• The molecular basis of cancer involves changes in cell physiology, classified oncogenes and tumor suppressor genes, activation/role of MYC in malignant transformation, and chromosomal abnormalities associated with neoplasms.
• Cancer can be caused by inherited germline mutations (5-10%), environmental carcinogens (15-20%), or spontaneous somatic mutations (70%).
• Chemicals, radiation, and pathogens are examples of environmental carcinogens.
• Tumor growth and progression involve initiation, promotion, and progression stages, with epigenetic and genetic alterations influencing these stages.
• The hallmarks of cancer include self-sufficiency in growth signals, insensitivity to growth inhibitors, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, ability to invade and metastasize, evasion of immune surveillance, and defects in DNA repair.
• Oncogenes promote cell growth, while tumor suppressor genes regulate growth.
• Tumor suppressor genes are inactivated due to mutations; oncogenes are activated by mutations.
• The cell cycle is regulated by cyclins and CDKs, which are regulated by CDK inhibitors.
• Proto-oncogenes are normal cellular genes that promote cell proliferation; oncogenes are mutant or overexpressed versions.
• Myc activates the expression of many pro-proliferative genes, directly controlling DNA replication, and playing a part in regulating cell growth, apoptosis, differentiation, and stem cell self-renewal.
• Chromosomal abnormalities include numerical abnormalities (aneuploidy, triploidy, tetraploidy) and structural abnormalities (deletions, duplications, inversions, insertions, translocations).
• Specific chromosomal abnormalities are associated with different cancers.
• Chromosomal translocations are rearrangements between chromosomes, resulting in gene fusions and associated cancers like Chronic Myelogenous Leukemia (CML).

Oncogenes

• Oncogenes are dominant gain-of-function mutations of proto-oncogenes, causing uncontrolled cell growth.
• Oncogenes are created by mutations (point mutation, translocation, gene amplification, activating mutation) in proto-oncogenes, promoting cell growth in the absence of growth-promoting signals.
• Oncogenes are categorized into growth factors, receptors for growth factors, cytoplasmic signal transducers, nuclear signal transducers, and cell cycle regulatory proteins.

Tumor Suppressor Genes

• Tumor suppressor genes normally regulate cell division, repair DNA damage and promote apoptosis, playing a protective role against cancer development.
• Inactivation of tumor suppressor genes leads to uncontrolled cell proliferation and cancer development. Examples include RB, p53, TGF-β and its receptor, APC and B-catenin proteins, and BRCA1 and BRCA2 proteins.