Lecture 19 - Cancer Treatment Flashcards
Why have some cancers become more treatable?
Ability to detect tumors early on, benign and malignant, has dramatically increased with technology.
Functional genomics has increased ability to predict tumor progression (can identify specific mutation, risk, and best treatment options).
How has cancer detection improved B-cell lymphoma treatments?
There are 3 different types of lymphoma, where different gene expression occurs.
Therefore, each type requires a different treatment instead of a single blanket treatment.
Why do tumor genetics cause an obstacle in treatment therapies?
Different lobes of the tumor can have different genetic makeups requiring different treatment strategies.
What are the 4 classic major strategies to cancer treatment?
1 - Surgery
2 - Radiotherapy
3 - Chemotherapy
4 - “Rational” agents (highly specific)
Chemotherapies: how they work, the effects they have, the drawbacks, etc…
Chemotherapies use antimetabolites that interfere with cellular metabolism. This decreases cellular stability and induces DNA damage and death.
Malfunctioning mitotic spindle: “Mitotic Catastrophe”
Alkylating agents and antibacterial agents can also induce covalent modification of DNA preventing transcription and replication.
Due to MBRI pumps, most solid tumors will eventually develop resistance to chemotherapies. Multidrug therapies ergo more efficient.
Downside: you kill a helluva lotta healthy cells in the process.
Current drug development: goals, preferences, etc…
Current drug development is aimed towards less toxicity to normal cells.
However, not all molecules are attractive targets.
Low-weight molecular compounds are preferred (easier to synthesize, greater ability to puncture tumor).
You also can’t make the compound too big or it won’t fit into the cell.
Most drug targets are enzymes who have druggeable active sites. Protein-protein interactions can be targeted.
Unfortunately, certain transcription factors such as Myc and Fas lack an active site that is druggeable.
What makes a good cancer treatment?
An effective treatment must be specific and not interact with normal cells/non-target proteins at effective dosages.
Designing Treatments: initial tests
Test performed to determine binding affinity and specificity to desired target.
Determine the required concentrations and off-target effects.
Designing Treatments: second step
Cell models are used to directly observe cellular effects and confirm dosage, specificity, and effect on healthy cell.
Designing Treatments: third step
Treatment tested on human cells transplanted into mice. Use highly aggressive cancer cell lines such as HeLa.
Designing Treatments: fourth step
How long does the drug last in the system, how long does it effectively bind its target (Pharmocodynoamics). Other side effects established
Designing Treatments: fifth step [final]
Human Trials:
Phase 1: small number of patients, wide range of doses in an aim to establish a therapeutic window. Range of concentrations higher than desired and lower than minimum. The larger between minimal effective and deadsies-ish the better.
Phase 2: larger number of patients, determine optimal patient type (age, tumor progression)
Phase 3: large scale increase in patients, many of which have highly progressed cancer stages. Very statistically significant. Comparison to current competitive form of treatment
Phase 4: not always performed. Specific sub-group studies for side effects etc… Usually occurs AFTER licensing. Safety.
