Oncology Biopharmaceuticals Practice Flashcards

Comprehensive practice flashcards covering biopharmaceuticals, monoclonal antibody categories, ADCs, and specific oncology drug profiles from the lecture notes.

Biopharmaceuticals (Biologics)

Large, complex pharmaceutical drug products manufactured in, extracted from, or semisynthesized from biological sources such as proteins, saccharides, nucleic acids, cells, or tissues.

Pros of Biopharmaceuticals over Small Molecules

High specificity due to binding overexpressed antigens on cancer cells, high potency from large surface molecular interactions, and a longer duration of action due to slow renal excretion.

Cons of Biopharmaceuticals over Small Molecules

High manufacturing expense, potential for immunogenicity (immune system over-activation), and limited tissue penetration due to large molecular weight.

Fab domain

The region of a monoclonal antibody containing the three complementarity-determining regions (CDR) in each variable chain that constitute the antigen binding site (paratope).

Fc domain

The region of a monoclonal antibody that modulates effector functions, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP).

IgG1 Molecular Mass

Approximately $150\,kDa$.

mAb Nomenclature: '-tu-'

Category 1 monoclonal antibodies that bind to antigens on the tumor cell surface (e.g., Cetuximab).

mAb Nomenclature: '-ci-'

Category 2 monoclonal antibodies that inhibit blood circulation in the tumor microenvironment.

mAb Nomenclature: '-li-'

Category 3 monoclonal antibodies that promote immune activities against cancer cells, named after the immune system and lymphocytes.

Cetuximab (Erbitux)

A prototype Category 1 mAb that inhibits EGFR (HER1) binding; requires EGFR expression and wild type KRAS for efficacy; used for colorectal cancer; toxicities include skin rash and hypersensitivity.

Trastuzumab (Herceptin)

A Category 1 mAb that inhibits growth factor binding to HER2; indicated for breast cancer with HER2 overexpression; carries risks of heart failure and embryo-fetal death.

LVEF (Left Ventricular Ejection Fraction)

A cardiac measurement that must be monitored during treatment with Trastuzumab (Herceptin) or Kadcyla due to the risk of heart failure.

ado-Trastuzumab Emtansine (Kadcyla)

An Antibody-Drug Conjugate (ADC) consisting of a HER2-targeting mAb linked to the microtubule inhibitor Emtansine to induce apoptosis in breast cancer cells.

Rituximab (Rituxan)

A prototype monoclonal antibody that binds to target CD20 on the surface of hematopoietic cells; used to treat hematologic malignancies like lymphoma and myeloma.

Bevacizumab (Avastin)

A Category 2 mAb that binds to vascular endothelial growth factor (VEGF) or its receptor to inhibit tumor angiogenesis; toxicities include hypertension, proteinuria, and impaired wound healing.

Biosimilar Drug

A drug product, such as Bevacizumab-awwb, that is chemically similar, clinically equivalent, exchangeable with, and usually cheaper than the original biologic agent.

PD-1/PD-L1 Pathway Inhibition

A mechanism of action where mAbs like Pembrolizumab (binds PD-1) or Atezolizumab (binds PD-L1) prevent cancer cells from suppressing T cells, thereby promoting an immune response.

Ipilimumab (Yervoy)

A Category 3 mAb that binds to CTLA-4 (cytotoxic T-lymphocyte associated antigen-4) to remove the 'brake' on T-cell activation; used for metastatic melanoma.

ir-AE (Immune-Related Adverse Events)

Toxicities associated with Category 3 mAbs (like Keytruda or Yervoy) where the immune system attacks normal cells, resulting in rash, colitis, or thyroid disorders.

Pegasparaginase (Oncaspar)

A PEG-modified enzyme that degrades asparagine in blood circulation to starve cancer cells of this nutrient; used to treat acute lymphoblastic leukemia (ALL).

REMS (Risk Evaluation and Mitigation Strategy)

A safety program required for patients taking Ipilimumab (Yervoy) due to the potential for fatal immune-related adverse events.