PART 1 : Cancer and Cell Cycle

The uncontrolled growth of cells that form a mass and invade nearby tissues.

The Edwin Smith Papyrus, a collection of medical texts from ancient Egypt, dating back to around 3000 BC, contains descriptions of tumors and treatments, suggesting early recognition of cancer.

Lifestyle factors, including diet, smoking, and physical activity, can influence cancer risk.

Chemical carcinogens, such as those found in tobacco smoke and certain industrial chemicals, can damage DNA and contribute to cancer development.

Viral infections, such as HPV (Human Papillomavirus) and Hepatitis B/C, can increase the risk of certain cancers by directly affecting cellular processes.

The G1/S checkpoint ensures that DNA is intact and nutrients are sufficient for DNA replication before the cell enters the S phase.

Growth factor signaling pathways, such as PI3K/Akt/mTOR, trigger the activation of Cdk4/6 and Cyclin D complexes during the G1 phase, promoting cell cycle progression.

E2F, a transcription factor, is released when Rb is phosphorylated, allowing the expression of genes necessary for DNA replication and cell cycle progression.

Cdk2/Cyclin A complex plays a crucial role in the initiation of DNA replication by recruiting helicase, which unwinds the DNA double helix.

The G2/M checkpoint ensures that DNA replication is complete and error-free before the cell enters mitosis.

Homologous recombination is a highly accurate DNA repair pathway that utilizes a complementary DNA strand as a template to repair double-strand breaks, restoring the original genetic sequence.

The MutS protein complex recognizes mismatched bases during DNA replication. This is a key step in accurate DNA repair.

Non-homologous end joining (NHEJ) is an error-prone DNA repair pathway that joins broken DNA ends without relying on a template, potentially introducing mutations.

BRCA1 plays a crucial role in stabilizing the repair complex for homologous recombination, ensuring accurate repair of double-strand breaks.

Ku proteins, along with DNA ligase, are involved in Non-homologous end joining (NHEJ) which is a critical step in repairing broken DNA strands.

When a proto-oncogene is mutated, it can become an oncogene that promotes uncontrolled cell growth, contributing to cancer development.

Tumor suppressor genes are involved in regulating cell growth and preventing uncontrolled cell division. Mutations or inactivation of tumor suppressor genes can contribute to cancer development.

BRCA1 is a well-known tumor suppressor gene that plays a crucial role in DNA repair, particularly in homologous recombination.

Mutations in BRCA1/2 genes are inherited in an autosomal dominant pattern, meaning that inheriting a single copy of the mutated gene increases the risk of developing cancer.

Cells with defective BRCA1/2 genes exhibit genomic instability, meaning their DNA is more susceptible to damage and errors, increasing the risk of cancer development.

PARP inhibitors exploit the synthetic lethality concept by targeting cancer cells with defective DNA repair pathways.

Synthetic lethality in cancer treatment involves targeting specific vulnerabilities in cancer cells due to defective pathways, leading to cell death.

p53, a tumor suppressor gene, responds to DNA damage by initiating apoptosis (programmed cell death) or cell cycle arrest, preventing the proliferation of damaged cells.

Myc, a proto-oncogene, is often hyperactivated in cancer, contributing to uncontrolled cell growth and proliferation.

The metaphase-to-anaphase checkpoint ensures that all chromosomes are properly attached to spindle fibers before the cell proceeds to anaphase. If chromosomes are not attached, Mad2 inhibits the anaphase-promoting complex (APC/C), halting cell cycle progression.

The S phase is the phase of the cell cycle where DNA synthesis and replication occur.

The Cdk1/Cyclin B complex promotes chromatin condensation during mitosis, preparing the chromosomes for separation.

Cyclin D activates Cdk4/6 in the G1 phase, contributing to cell cycle progression.

Ras, a small GTPase, activates the MAPK pathway in response to growth factors, leading to cell proliferation and differentiation, but can contribute to cancer if it's mutated.

Homologous recombination is most effective in repairing double-strand breaks, particularly in the S and G2 phases of the cell cycle.