Cancer Immunotherapy Overview

Most p53 mutations are missense mutations, meaning a single nucleotide change alters a single amino acid in the protein.

Apoptosis is programmed cell death, while necrosis is accidental cell death characterized by inflammation.

Phosphorylation of p53 increases its activity, while phosphorylation of Mdm2 degrades it, leading to p53 stabilization during cellular stress.

p53's short half-life in normal cells prevents excessive activation and damage to healthy cells outside of stressful situations.

First-generation CAR T-cells use a CD3 signaling domain to activate the T-cell receptor.

Third-generation CAR T-cells add a survival domain to improve persistence and survival of the genetically modified T-cells.

The most common Ras mutation is Glycine 12 → Valine, which disrupts GTP hydrolysis and leads to constitutive Ras activation.

Growth factors binding to receptors trigger tyrosine phosphorylation, activating Ras through SH2 domain interactions.

Keytruda (an anti-PD-1 antibody) boosts the immune system to fight cancer by restoring its ability to target tumor cells.

PD-1, a protein, regulates the immune system's self-tolerance, which cancer cells exploit to hide from attack.

Programmed cell death, crucial for getting rid of damaged cells, preventing disease, and maintaining healthy tissue

p53, a protein, is a major guardian against cancer; it acts as a safeguard, initiating cell death pathways when cells are damaged.

Mutations in p53, a protein that normally inhibits tumor growth, are frequently observed in cancer cells; they often disrupt the protein's ability to activate cell death processes, allowing cancer to thrive.

Immunotherapy using dendritic cells for prostate cancer, extending survival by adding back cancer-fighting cells to the body.

Keytruda works by bolstering the immune system, while Provenge utilizes dendritic cells to deliver cancer-fighting messages directly.

Proteins that prevent cells from dying (apoptosis).

Cancer development requires multiple mutations.

Mutation in APC gene causes colon polyps, higher risk of cancer.

Changes in genes cause uncontrolled mutations in cells.

The process of forming a tumor (cancer).

Mutations that promote cancer growth and survival.

The process that activates caspase, initiating apoptosis.

The formation of new blood vessels, crucial for supplying nutrients to growing tissues.

Genes rapidly activated by growth factors, key for initiating cell division.

Uncontrolled cell division, a step in cancer development.

Cancer cells avoiding growth arrest, allowing them to continue dividing.

Cancer cells' ability to avoid programmed cell death.

Cancer cells losing their ability to stick to neighboring cells, enabling metastasis.

A protein normally in mitochondria; released during apoptosis, activating cell death.

A protein that prolongs cell survival, often overexpressed in cancer cells.

Inflammation creates an environment that fosters cancer growth by promoting interactions between cells and increasing mutation rates.

Genomic instability increases the heterogeneity and adaptability of tumors, making them more resistant to treatment.

Constant stimulation of cell division is a key driver for many cancers.

A wasting syndrome caused by systemic effects from something distant from the tumor (paraneoplastic syndrome).

Cachexia affects a large percentage of cancer patients and is a major cause of death.

Targets specific molecular changes in cancer cells, improving treatment effectiveness and reducing side effects.

Traditional approaches to cancer treatment target general cell division and progression and can be effective but may cause side effects like secondary cancers

Analyzing breast cancer using microarrays to identify genetic subtypes for potential personalized treatment options.

Microarrays are used to analyze gene expression patterns in cancer cells, helping classify different subtypes and guide personalized treatment strategies.

RNA sequencing (RNA-seq) is a newer, more detailed method than microarrays for analyzing gene expression, providing a comprehensive view of RNA transcripts in cancer cells.

Differentiation therapy aims to induce cancer cells to differentiate into normal cells instead of killing them, effectively exiting the cell cycle and reducing cancer growth.

Small molecule drugs target intracellular oncogenes, often inhibiting their activity. They can enter cells and affect internal processes.

Monoclonal antibodies target extracellular proteins associated with cancer, such as surface markers or secreted factors, disrupting cancer signaling or growth.

Cancer treatments undergo rigorous development, starting with laboratory testing, animal studies, and clinical trials in phases I, II, and III to ensure safety, efficacy, and proper dosage.

Cancer cells can develop resistance to treatment through mechanisms like protein mutations, gene amplification, or altered drug metabolism, which allow them to circumvent the effects of therapy.

Cancer management is shifting towards treating it as a chronic disease, focusing on extending remission periods, managing relapses, and improving quality of life.