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Cancer BIO Exam 3 Flashcards

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1
Q

5 Approaches to Cancer

A

Surgery
Radiation oncology
Chemotherapies
Targeted therapies
Immunotherapies

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2
Q

Surgery— how it’s used to approach cancer?

A
  • surgeries to attempt to remove or cauterize tumors
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3
Q

Breast cancer metastasis patterns

A
  1. Escape from primary tumor and local invasion
  2. Intravasation and survival in circulation
  3. Extravasation and metastatic seeding
    * But metastases move to distal sites through the bloodstream rather than expanding locally
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4
Q

*treating cancer with surgery as soon as possible than using therapy first before surgery has more survival

A
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5
Q

Neoadjuvant therapy (drug treatment before surgery) vs. Adjuvant
therapy (treatment after surgery)

A

Neoadjuvant
*Neoadjuvant therapy is treatment before tumor removal
* Helps shrink the size of tumors making them easier to cut out
* Delay in surgical removal of the tumor could mean the cancer
spreads

Adjuvant
*Adjuvant therapy is treatment after
tumor removal
*Can help prevent cancer returning and kills off remaining cancerous cells
*The treatments can weaken the person further due to unpleasant side
effect

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6
Q
  • Bioimaging helps surgeons precisely locate tumors
  • They can know which cell is normal or cancer and so they can precisely cut the tumor cells
A
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7
Q

Radical Mastectomy:
They would take the whole breast and part of lymph node, take as much as they could, so they can get to all the cancer cells

A
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8
Q

*virtual surgical planning:
Providing a virtual plan on how to take out tumors
* Remote robotic surgery—becoming popular, where a robot does it and doctors watch or monitor

A
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9
Q

Radiation and radiation oncology:
*radium as cancer therapy
* Radium is radioactive emmiting radiation nearby cancer cells *Radiation is localized so it does not affect neighborng cells

A
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10
Q

*radium is cancerous
* Massive cancer incidence in 1920s radium-based watch factory workers who routinely licked the paintbrushes touching radium
* Radiation is extremely toxic to cells.

A
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11
Q

Can radiation therapy be used to more specifically target cancer cells?

A

*They were using pellets or radiation shooting lasers to tumor cells to kill the cancer cell
* Coutard method of time/dose fractionated treatments (splitting the dose decreased effect on healthy cells)

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12
Q

Radiation therapy to induce apoptosis:

A
  • Radiation therapy aims to overwhelm cancer cells with DNA damage to induce apoptosis of targeted cancer cells
  • Radiation—apply dna damage and p53 can be triggered and hopefully kill the cancer cells through apoptosis
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13
Q

How can radiation therapy help against cancer?

A

Radiation factors (total dose, number of fractions, radiation quality)—we can control it

Microenevironment factors (O2 tension, serum deprivation, pH)

Cell intrinsic factors—(cell type, phase of cell cycle, p53 and ATM status)

Having intact p53 is important if using radiation/dna damage, to induce apoptosis

Killing blood vessel can induce cell death

Cancer cells that dies release factors that attract immune response

Neoantigens new mutations from radiation (immune system can see this and attack these cells or apc presenting tumor cells)

Indirect radiation effect—injury of tumor vasculature (lead to hypoxia then cell death), heightened anti tumor immune response (immune mediated cell killing)
Direct radiation effect—cancer cell death (release of DAMPs, result in immunogenic cell death)

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14
Q

Early computational radiation oncology (1980s):
*Three-dimensional dose calculation and radiation planning to hit cancer from two or more axes
* Scanning and adjustment during radiation therapy

A

Modern radiation therapy helps against triple negative breast cancer

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15
Q

Artificial intelligence enhanced radiation oncology

A

Train ai on thousand of images of people’s tumors, then teach the computer what a tumor looks like and they show different images and see if they can identify a treatment for a specific region

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16
Q

Influences of Artificial Intelligence on modern radiation oncology workflow​
—see lec 19 powerpoint slide 23

A
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17
Q

but radiation therapy against breast cancer increases the risk of later-life lung cancer​

*With radiation treatment, developing another cancer (from breast to lung) is more likely than without Rt​

Rt increases the development of another cancer much later

A
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18
Q

Dose-response curve​

A

*They take a cancer cell line
*Change the dose and measure the response of cancer cells (dose-response curve)​
*they see that more dosage of drugs administered kills more cancer cells

​

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19
Q

IC50​–inhibitory contraction 50%

A

the concentration of drug required to inhibit a phenotype of interest by 50%

extra (outside info):
*The lower the IC50 value, the more potent the drug is at inhibiting the target function
*Researchers use IC50 values to compare the effectiveness of different drugs or to optimize the dosage of a particular drug for maximum therapeutic effect while minimizing side effects.

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20
Q

Therapeutic window​

A

Therapeutic window—where you kill cancer cells but not much of normal cells​

So you wanna limit chemo or drugs to not target as much normal cells​

Target good response for cancer cells but not for normal cells—in terms of drug administration

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21
Q

No therapeutic window = Toxicity to normal cells​

A

either the dose is too low to be effective against cancer cells or the dose is too high it becomes toxic to normal cells

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22
Q

Drug combinations​

A

*Often the combination of two drugs works better than one drug or the other drug alone​
*Drug 1+drug 2=synergistic effect (more effective because of low IC50–drug more potent)

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23
Q

Identifying synergistic combination therapies​
also see illustration in lect 20, slide 11

A

(drug 1)High+(drug 2) high =high effect​

Low+low=low effect

You want drugs that are synergistic together​

Sometimes medium dose is better than higher dose​

3 drugs combined worked better although more toxic

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24
Q

The advent of combination chemotherapy​

A

Vincristine​ + Amethopterine​ + Methotrexate​ + Prednisone​ =VAMP

*VAMP was effective against leukemia and increased kids’ survival​

*…but VAMP did not help against brain metastases​
because most chemos have trouble crossing the blood-brain barrier​

*Concern about toxic side effects of this kind of approach led to a huge debate about patient welfare ​

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25
Q

chemo side effects

A

fatigue
hair loss
kidney problems
weight loss
risk of bleeding and bruising
infection
anemia
muscle pain
more…see lec 20 slide 13

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26
Q

is chemo worth it?

A

*Overall survival is improved by chemo​

Cancers mutate around the drugs that are being administered​

But these drugs are not perfect that’s why we haven’t killed every cancer

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27
Q

Mechanisms of chemotherapeutic efficacy​

A

*alter function of microtubules=cell arrest
*alter function of respiratory chain= increased ROS
*inhibition of mDNA replication/transcription= alter mitochondrial function= activation of apoptosis
*inhibition of DNA replication/mRNA transcription= cell arrest/death
*macrophages/T cell/monocytes release of pro-inflammatory cytokines and activation of apoptotic pathways = cell death

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28
Q

Agonists and antagonists​

A

Agonists: Drugs that occupy target and activate it—activator of target​
ex: an agonists could be a ligand mimic which binds a receptor to have a similar activating effect to the natural ligand​

Antagonists: Drugs that occupy target and block its activation—make the activation less
ex:an antagonist could bind the receptor to physically prevent the ligand from activating it​

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29
Q

Allosteric modulation​

A

Allosteric interactor do not directly bind to the active site​, but influences whether a substrate is able to bind an active site

Substrate—binds to target​

Allosteric inhibitor-binds and prevents substrate from binding to target​

Allosteric Activator—helps target binding

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30
Q

Competitive and non-competitive inhibitors​

A

Competitive inhibitor: The inhibitor reduces the enzyme activity by competing with another substrate to bind.​

Non-competitive inhibitor: The inhibitor reduces the enzyme activity, and the inhibitor binds equally well to the enzyme regardless of whether the enzyme is bound to the substrate or not.—like allosteric interactor

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31
Q

Pharmacology: Kd​

A

The equilibrium dissociation constant Kd is the concentration value when 50% of receptors are occupied​

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32
Q

Estrogen in breast cancer​

A

estrogen bound to estrogen receptor in breast cell + coactivator protein = cell proliferation
*Estrogen binding—prowgrowth signal

Tamoxifen is a small molecule originally synthesized in the 1960s in an attempt at creating an antiestrogen contraceptive. ​
​
Tamoxifen inhibited the estrogen receptor, but did not have contraceptive activity in humans.​
​
Tamoxifen was nearly scrapped, until it was realized that the estrogen receptor was also important for breast cancer and clinical experiments began.

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33
Q

Tamoxifen cell-type dependent mechanisms of action​

A

tamoxifen can act as antagonist in breast cancer, blocking estrogen binding = no proliferation occurs

tamoxifen can act as an agonist in endometrial cell, tamoxifen binds to estrogen receptor and coactivator in endometrial cell= cell proliferation occurs

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34
Q

Herceptin​

A

herceptin+ have receptor which enables herceptin to bind=advantage for individuals needing chemotherapy using herceptin

outside info:
This is because the presence of more HER2 receptors increases the likelihood of Herceptin binding to the cancer cells, leading to a more effective inhibition of their growth and potentially improving treatment outcomes for these individuals

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35
Q

Iterating mechanisms of Her2 inhibition​

A

I,ii,iii,iv==domains of her2​

Adcc (antibody-dependent cell-mediated cytotoxicity or NK cells)= triggering of immune system​—-Natural killer (NK) cells lyse their targets​

High her2—recognized by immune system
Dimerization domain that is blocked inhibit dimerizing​

Antibody (orange) only target cancer cells but target the one with her2​

Kinase domain I inhibitors==mimics and binds to kinase to inhibit it (like putting gum in the ears)​

Bispecific antibody=two different regions=hit 2 different targets

my info:
a)
*pertuzumab–inhibit eceptor dimerization
*her2 inhiibiton involves promotion of receptor internalization and degradation
* trastuzumab, margetuximab—helps in engagement of ADCC
b)
*trastuzumab emtansine, trastuzumab deruxtecan are an example of targeted delivery of highly cytotoxic agents
*lapatinib, afatinib, neratinib–direct inhibition of the downstream tyrosine kinase domain
c)
bispecific antibody–dual targeting of the trastuzumab and pertuzumab binding sites

—all these help inhibit P13Kinase signaling and promote cell cycle arrest

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36
Q

Chronic myelogenous leukemia (CML)—too many lymphocytes​

A

BCR (chromosome 9)-ABL(chromosome 22) translocations turn out to be the single cause of virtually every case of CML​

one hit cancer

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37
Q

How does BCR-ABL drive leukemia​

A

ligand binding>JAK2>phosphorylated STAT5 = cell growth and proliferation

BCR phosphorylate GRB2/SOS/GAB2>P13K>AKT ….pathways =cell growth and proliferation

SMO>Gli1 = cell growth and proliferation

FRZL>beta catenin=cell growth and proliferation

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38
Q

Imatinib as a CML treatment​

A

targeted therapy has shown more survival than chemo

ex: imatinib, binds to bcr abl and acts as an inhibitor

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39
Q

Lock and key: Imatinib as a BCR-ABL inhibitor​

A

imatinib binds to the pocket in BCR-ABL, where ATP binds to drive CML

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40
Q

Building new generations of BCR-ABL inhibitors to target observed resistance mutations ​

A

Resistance mutation around the same area where drugs bind​

Dasatanib=another drug that caters to another mutation where imatinib didn’t work​

Ponatinib=another better drug, where it cleans up the mutations that escaped the previous drugs

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41
Q

Point mutations in RAS drive 15-30% of all cancers​

A

Switch I and ii depends on whether gtp or gdp is bound

42
Q

Selectively inhibiting KRAS G12C​

Inhibiting KRAS: Many approaches to a single target​
maybe ask in office hours

A

*GDP selective inhibitors covalently targeting G12C, G12R, or G12S
*GDP selective inhibitors non-covalently targeting G12C, G12D, or pan-KRAS

*GTP selective inhibitors targeting G12C

*compounds recruiting CYPA to G12C or pan-KRAS
*CYPA blocks raf from binding

*GDP selective PROTACs targeting G12C for degradation

43
Q

Proteolysis targeting chimera (PROTAC)​

A
  1. PROTAC binds POI
  2. PROTAC binds E3 ligase
  3. E3 catalyzes polyubiquitin signal on the POI
  4. proteosomal degradation of poly-ub POI
    result: destruction of oncogenic protein
44
Q

Fusion and bispecific antibodies to recruit PROTACs (or other drugs) to cancer cells​

A
45
Q

Many receptor tyrosine kinases are good drug targets
* anti-cancer therapies directly targeting each of the rtks have been tested and are mostly currently in clinical use
See lec 21, slide 2

A
46
Q

EGFR ligands and inhibitors

See lec 21, slide 3

  • Erbb kinase inhibitors are dirty drugs—hit multiple things
A
47
Q

Inhibiting angiogenesis by targeting VEGFR

  • Many drugs can block vegf =nonfunctional downstream kinase signaling angiogenesis
    See drug examples on slide 4 lec 21
A
48
Q

Androgen Receptor signaling in prostate cancer

Outside info:
* Androgen receptor (AR) signaling plays a crucial role in prostate cancer development and progression.
* In prostate cancer, AR signaling becomes dysregulated, leading to uncontrolled growth and survival of cancer cells. This can occur through various mechanisms, including mutations in the AR gene, increased expression of the AR protein, or alterations in androgen production or metabolism.
*Targeting AR signaling is a key strategy in the treatment of prostate cancer, with therapies aimed at blocking the AR or reducing androgen levels to inhibit cancer growth

*high AR=high psa= indication of prostate cancer
* see signaling pathway on slide 5 lec 21

A
49
Q

Androgen receptor as a target in prostate cancer

*abiraterone acetate blocks conversion of testosterone to dht, so AR wont be activated
*enzalutamide/apalutamide/darolutamide—blocks AR from bbndimg to ARE and downstream signaling

  • enzalutamide has shown great survival rate when administered to prostate cancer
A
50
Q

RAF dimerization and mutations

A
  • growth induced, RAS dependent BC raf dimers–normal activation only when ras is present
  • constitutive RAS dependent BC raf dimers—ras is mutated and ras is always on, so constant activation
  • nonv600 B-raf mutants (self dimer)—even without ras, braf can self dimerize and becomes activated
  • v600 B-raf mutants (monomers)—can be activated only by itself
51
Q

Lock and key: Vemurafenib inside BRAF

A
52
Q

Paradoxical RAF activation and alternative ways to inhibit RAFs

*raf inhibitor induced paradoxical ERK cascade activation
*pan-raf monomer/dimer inhibitor
*non dimer promoting raf inhibitors

Ask during office hours

A
53
Q

Early BRAF inhibitors worked for a while, then relapsed

Slide 10-11

A
54
Q

Targeted inhibitors of RAS/PI3K pathway in melanoma

A

*RTK inhibitors block RTK
*vemurafenib and dabrafenib and glx818 block braf v600

  • trametinib and cobimetenib and mek162 block MEK

*erk inhibitors boock erk
* p16 block cyclin D
* cdk4 knhibitors block cdk4/6= in inactivates RB1= more growth

*mdm2 block p53 = more growth

*p13k inhibitors (bkm120, gdc0941, sar245409, bez235, temsiromolus, everolimus)— they inhibit p13k, akt, mtor

*epigenetic regulators inhibit growth

55
Q

mTOR inhibitors

  • Mtorc1 activate mrna translation, activates apoptosis
A

*rapamycin and rapalogs inhibit (mtor, raptor g-beta-l)—- inhibit mrna translation (effect on g1 to s cycle) but on its effect on apoptosis, bad and bcl2 goes to become activated(oncogenic pathway) as p53 is inactivated (so apoptosis doesn’t happen)

56
Q

Rapamycin is an mTORC1 inhibitor that blocks translation, growth, and proliferation

  • ..but rapamycin also activates negative feedback leading to undesirable reactivation of oncogenic signaling
A
57
Q

Next generation rapalog inhibitors target both mTORC1 and 2

A

*torin1– a mTOR signaling inhibitor
* Inhibiting both complexes decreases negative feedback= inhibit further growth, activate autophagy, inhibit glucose and lipid metabolism

58
Q

Targeted agents in breast cancer target therapies

A

*mapk
*akt
*parp
*mtorc1
*rtk
*p110
*src

  • parp inhibitors triggers apoptosis, involved in dna damage repair
59
Q

Inhibitors of histone deacetylases de-repress tumor suppressor genes

*histone deacetylation (hdac)—condensed chromatin— transcriptional repression
* histone acetylation (hat)— relaxed chromatin—transcriptional activation

A
60
Q

Inhibitors of ezh2 inhibitor cancer at the epigenetic level

A

*ezh2 inhibits lineage specification genes, pRB tumor suppressor, dna damage repair genes= activated differentiation, proliferation, genetic mutations

Outside info:

The action modes of EZH2. (1) EZH2 catalyzes H3K27me3 dependent on PCR2, which contributes to transcriptional silencing. (2) EZH2 is also capable of methylating several non-histone protein substrates (e.g. STAT3, GATA4, talin, and RORα), which contributes to both transcriptional silencing and transcriptional activation. 3) EZH2 also has a PRC2-independent role in transcriptional activation, acting as co-activator for transcription factors

61
Q

Hematopoietic stem cell is divided into lymphoid and myeloid progenitor

Lymphoid is composed of any adaptive components of immune response like b cell and t cell

Myeloid is composed of innate like macrophages and neutrophil

A
62
Q

Tumor cells and the immune microenvironment interact

How can we turn immune system against cancer?

A

Immunotherapy—turns immune system against cancer

63
Q

Ctla4—checkpoint inhibitor (inhibit “turn off attack mode”)

A
64
Q

Categories of immunotherapy

Seeslide 6 lec 22

A
65
Q

Autologous bone marrow transplant

  • Method of replenishing immune system after chemo or radiation
    …but it turns out these immune cells also help attack tumors
  • An autologous stem cell transplant replaces a patient’s stem cells that were destroyed by treatment with radiation or high doses of chemotherapy
A
66
Q

Treating cancer by stimulating T-cells with interleukin-2 (IL-2)​

A
67
Q

Antibodies inhibiting CD20 trigger the immune system​
to attack B-cells, useful for patients with B-cell lymphoma​

A
  • High expression of CD20 on the cell surface is one of the defining characteristics of B-cells ​
  • Rituximab is a therapeutic anti-CD20 antibody that binds to B-cells to recruit NK cells and macrophages for antibody dependent cytotoxicity (ADCC)​
68
Q

CXCR proteins facilitate communication​ between cancer and the microenvironment​

A

inhibiting cxcr4 results in anticancer responses

69
Q

Potential mechanisms of CXCR4 inhibitors​

A

cxcr4 inhibits:
*TAM polarization
*recruitment
*metastasis
*cxcl12 binding to cxcr4, which will activate ERK and AKT pathway (associated with proliferation and angiogenesis)

70
Q

Immune checkpoints:​

Activating and inactivating interactions between APCs and T-cells​

A

*ctla4 binding to b71/2=cd28 cannot bind to b71/2 so no t cell activation=no immune response
*pd1 binds to pd1l1/2 to recruit shp2=inhibits t cell signaling

71
Q

Antibodies blocking CTLA-4 activity helps T-cells go on the attack ​

A
72
Q

PD-1 or PD-L1 antagonists activate T-cells to attack tumors​

A

*pdl1 binds to pd1 and inhibit t cell killing of tumor cell
*blocking pdl1 or pd1allows t cell killing of tumor cell

73
Q

High pre-existing immune infiltrate of T-cells observed in pre-treatment biopsies​ correlates with probability of immunotherapy success ​

*hot or inflamed=means more response to immune checkpoint inhibitors

outside:
Immunotherapy works best for tumors that already have immune cells close by; these tumors are sometimes called “hot” or “inflamed” tumors. Immunotherapy does not work in many people with breast cancer, in part because these tumors have low numbers of immune cells and are considered “cold” or “not inflamed”

A
74
Q

Factors that influence efficacy of immunotherapy​

A

More mutations = More neoantigens for immune cells to see = More sensitive to immunotherapy​

cold vs hot tumor

75
Q

What can you combine with an immunotherapy?​

A

*other checkpoint inhibitors
* targeted therapy
* inhibition of angiogenesis
*intratumoural response (increased t cell infiltration)
*chemotherapy
*radiation therapy
*vaccines and adaptive t cell therapy

76
Q

Some forms of immunotherapy aim to convert tumors from “cold” to “hot” by recruiting immune cells​

A
77
Q

T-VEC (Talimogene laherparepvec (T-VEC)​: oncolytic virus against melanoma​

A

Replaced chunks of Herpes virus sequence with Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF—attract immune response)​

Better at attracting immune response​

Deleted sequences make virus deficient at spreading to infect neighboring normal cells and causing blisters​

Direct local injection into site of melanoma​
78
Q

Early ways to engineer immune cells​

A

*Sipuleucel-T: Adding GM-CSF into monocytes​ before autologous transplant as a therapy for prostate cancer​

79
Q

Chimeric Antigen Receptor T-cell (CAR-T) therapy​

A

*remove blood from patient to get t cells
*make car t cells in the lab
*grow millions of car t cells
*infuse car t cells into patient
*car t cell binds to cancer and kill them

80
Q

Where should the T-cells used for CAR-Ts come from?​

Personalized vs. Off-the-shelf approaches​

A

Autologous:
*Rejection of T-cell transplant unlikely​
*Can personalize CAR-T targets to match the specific tumor’s antigen profile​
Allogeneic:
*One donor can treat many patients. Mass production and off-the-shelf creates simpler logistics. ​

​

81
Q

Anti-cancer vaccines​

A

“Vaccine” means immunostimulatory, not necessarily preventative ​

outside:
the primary function of a vaccine is to stimulate the immune system rather than solely prevent infection or disease

82
Q

BiTE: Bispecific T-cell Engagers​

A

A BiTE is a therapeutic that combines the specific part of a T-cell binding antibody​ with the specific part a tumor cell binding antibody to recruit T-cells to the tumor cells ​

83
Q

Early attempts: inhibiting FTase to prevent RAS membrane localization​

A

FTases failed clinically against KRAS mutant cancers​ because farnesylation can be functionally replaced by geranylgeranylation​

84
Q

HRAS lacks alternative prenylation​

A

*RAS signaling depends on membrane localization
*Tipifarnib is an FTI that blocks farnesylation—membrane localization
*alternative modification by geranylgeranyl transferase enables kras/nras to escape FTI
*hras depends on farnesylation
*FTI clinical trials for HRAS-driven head and neck squamous cell carcinoma​

85
Q

KRAS G12C covalent inhibitors​

A

KRAS G12C:
*MRTX849 covalently binds to the cysteine and an induced switch II pocket
*KRAS G12C is irreversibly locked in inactive state

86
Q

Basket trials of KRAS(G12C) inhibitors​

A

*KRAS G12Ci in non-small cell lung cancer (NSCLC)​—approved
*The same KRAS G12Ci in colorectal cancer (CRC)​—failed

*Tissue specificity context can impact efficacy of targeted therapy​

87
Q

Resistance to KRAS inhibitor AMG-510​

A
88
Q

response to KRAS inhibitions
*On-target genetic change: Deletion of KRAS G12C​
*​Off-target genetic alterations in other genes can also drive resistance​

A
89
Q

Methods of exploring mechanisms of resistance to KRAS inhibitors​

A

*viability/growth assays
*sequencing for CRISPRi enrichment/depletion
*RNAseq and viability assays

90
Q

KRAS G12Ci + X​

A

Based on preclinical data and educated guesses, combination KRAS G12Ci clinical trials are underway for inhibitors of EGFR, PD-1, SHP2i, CDK4i, SOS1i​

91
Q

Resistance to KRAS G12C covalent inhibitors suggests combo strategies​

A

*MRTX849 inhibits KRAS G12C, which suppresses MAPK/ERK signaling and tumor growth
*hyperactivation—-inhibiting ERK hyperactivates RTK signaling through regulation of pathway genes
*combination strategy—combinaions of MRTX849 and EGFR or SHP2 inhibitors combat upstream reactivation of the RAS pathway and demonstrate increased anti-tumor activity

92
Q

drug tolerant persister (DTP) cells

A
  1. treatment-naive drug sensitive cells
  2. cells become drug tolerant persister
  3. after continuous treatment, tumors still are resistant (they develop secondary mutations, gene amplification, activation of bypass pathway, and other resistant mechanism)
93
Q

Multi-drug resistance exporter pumps​

A

*Drugs don’t work if they can’t reach their targets in the cell​
*Some cancer cells upregulate multi-drug resistance pumps to escape therapy​

94
Q

Resistance mechanisms to immunotherapy​

A

response:
*formation of tumor reactive t cells
*activation of effector t cell function
*formation of effector memory t cells
resistance mechanisms:
*lack of sufficient or suitable neo antiens
*impaired processing or resentation of tumor antiens
*impaired intratumoral immune infiltration
*impaired IFN signaling
*metabolic/ inflammatory mediators
*immune suppressive cells
*alternate immune checkpoints
*severe t cell exhaustion
t cell epigenetic changes

95
Q

vegf binds to vegfr 1/2 > activates p13k,raf, src pathway. Then leads to vascular permeability, cell proliferation, cell motility =angiogenesis

A
96
Q

Anti-angiogenesis therapies​:
*reduction and normalization of blood vessel network=transient hypoxia

how tumors get around them:
**alternative pro-angiogenic pathways
**neo-angiogenis– independent mecahnisms​ of blood vessel formation
**escape from hypoxia
**involvement of tumor associated stromal cells
**tumor cell adaptation to energy stress

A
97
Q

Resistance to CAR-T cell therapies​

A

*antigen escape
*t cell exhaustion

98
Q

Cytokine Release Syndrome​

A

outside:
A condition that may occur after treatment with some types of immunotherapy, such as monoclonal antibodies and CAR-T cells. Cytokine release syndrome is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy

99
Q

Combinations to prevent cytokine release syndrome toxicity​

A

*anakinra combined with tocilizumab could be useful for preventing severe cytokine release

100
Q
A

Biology (3 decks)

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