Watch the slideshow: https://youtu.be/TP7iP1HEVps Learn key concepts: Hallmarks of cancer, Angiogenic switch, Tumor Angiogenesis VEGF family i.e ligand and receptors, Effect of VEGF VEGF Inhibitors or angiogenic Bevacizumab, Ramucirumab, Ziv-Aflibercept

1. VEGF inhibitors In
Cancer therapy
Dr. Dhriti Gupta, MD
Clinical Extern
Under Supervision Of Dr. Ratesh Khillan
Brooklyn Cancer Care
Brooklyn, NY
October 5, 2021

2. The Hallmarks of
Cancer
Cancer is tissue disorganization.
Biological behaviors of cancer
are:
→ invasion
→ metastasis
REVIEW| THE CELL, VOLUME 100, ISSUE 1, P57-70, JANUARY 07, 2000

3. BRITISH JOURNAL OF CANCER (BR J CANCER) ISSN 1532-1827 (ONLINE) ISSN 0007-0920 (PRINT)

4. Tumor Angiogenesis
HTTPS://WWW.GENENTECHONCOLOGY.COM/PATHWAYS/CANCER-TUMOR-TARGETS/VEGF.HTML

5. Tu m o r A n g i o g e n e s i s
Thrombospondin
Angiostatin
Endostatin
VEGF
PDGF
Angiopoietin
HTTPS://WWW.NOVUSBIO.COM/RESEARCH-AREAS/CANCER/ANGIOGENESIS
TSP-1

6. VEGF
family and
signalling
pathway.
Vascular Endothelial Growth Factor
(VEGF)
Stimulates vascular endothelial:
→ cell growth
→ survival
→ proliferation
HTTPS://WWW.GENENTECHONCOLOGY.COM/PATHWAYS/CANCER-TUMOR-TARGETS/VEGF.HTML
Angiogenesis is mediated primarily through the interaction of
VEGF-A with VEGFR-2.

7. VEGF
family and
signalling
pathway.
Vascular Endothelial Growth Factor
(VEGF)
Stimulates vascular endothelial:
→ cell growth
→ survival
→ proliferation
HTTPS://WWW.GENENTECHONCOLOGY.COM/PATHWAYS/CANCER-TUMOR-TARGETS/VEGF.HTML
Angiogenesis is mediated primarily through the interaction of
VEGF-A with VEGFR-2.

8. VEGF
family and
signalling
pathway.
Vascular Endothelial Growth Factor
(VEGF)
Stimulates vascular endothelial:
→ cell growth
→ survival
→ proliferation
HTTPS://WWW.GENENTECHONCOLOGY.COM/PATHWAYS/CANCER-TUMOR-
TARGETS/VEGF.HTML
Activate secondary angiogenic pathways:
 Basic fibroblast growth factor (bFGF)
 Transforming growth factor beta (TGFβ)
 Placental growth factor (PlGF)
 Platelet-derived endothelial cell growth factor (PD-ECGF).

9. Tumor Neo vasculature

10. CELL DEATH & DISEASE (CELL DEATH DIS) ISSN 2041-4889 (ONLINE)

11. EFFECT OF ANTI-ANGIOGENIC THERAPY

12. 1) neutralizing monoclonal antibodies against VEGF or
its receptor,
2) small molecule tyrosine kinase inhibitors of VEGF
receptors,
3) soluble VEGF receptors which act as decoy receptors
for VEGF, and
4) ribozymes which specifically target VEGF mRNA.
VEGF INHIBITORS

13. VEGF INHIBITORS
(ANTI-ANGIOGENICS)

14. Bevacizumab (Avastin)
 Humanized monoclonal
antibody targeting VEGF
 Inhibition of VEGF
signalling via bevacizumab
treatment
 Normalize tumor
vasculature
 Promoting a more
effective delivery of
chemotherapy agents
HTTPS://WWW.CANCER.GOV/ABOUT-CANCER/TREATMENT/DRUGS

15. Metastasized Colorectal cancer
Fluorouracil
Improved
response rates
from 35% to
45%
Not effective as
adjuvant therapy.
1st/2nd
Fluoropyrimi
dine
Irinotecan
hydrochloride
or oxaliplatin
as second-line therapy in
patients whose disease
has gotten worse after
therapy that included
bevacizumab.
Worse
HTTPS://WWW.CANCER.GOV/ABOUT-CANCER/TREATMENT/DRUGS

16. Nonsquamous non-small cell lung cancer
Locally
advanced
Cannot be
removed by
surgery
Metastasized, or
recurred
Advanced
NSCLC
Carboplatin
Paclitaxel
1st line
Significant
improvement in
median survival
Significantly
higher response
rates.
Results
HTTPS://WWW.CANCER.GOV/ABOUT-CANCER/TREATMENT/DRUGS

17. Other uses
Cervical cancer
Advanced
Metastasized
Reoccurrenc
Paclitaxel
Cisplatin or
topotecan
hydrochloride
Glioblastoma
Recurrent
Only phase II
trial
Hepatocellular
carcinoma
Advanced
Atezolizuma
b
Ovarian
epithelial cancer
Stage III,
stage IV, or
Recurrent
disease
Renal cell
carcinoma
Metastasize
d
Interferon
alpha
HTTPS://WWW.CANCER.GOV/ABOUT-CANCER/TREATMENT/DRUGS

18. RESEARCHGATE

19. Fatal Adverse
Effects:
RESEARCHGATE

20. Withhold for at least 28 days prior to elective surgery.
Do not administer Avastin for 28 days following major surgery and
until adequate wound healing.
COMMON SIDE EFFECTS
(incidence > 10%)
 Epistaxis
 Headache
 Hypertension
 Rhinitis
 Proteinuria
 Taste alteration
 Dry skin
 Hemorrhage
 Lacrimation disorder
 Back pain
 Exfoliative dermatitis
RELATIVE CONTRAINDICATIONS
 Gastrointestinal Perforations and Fistula
 Surgery and Wound Healing Complications
 Hemorrhage (Do not administer for recent
hemoptysis.)
 Arterial or Venous Thromboembolic Events
 Uncontrolled Hypertension
 Renal Injury and Proteinuria
 Infusion-Related Reactions
 Embryo-Fetal Toxicity or Ovarian Failure
 Congestive Heart Failure (CHF)
HTTPS://WWW.CANCER.GOV/ABOUT-CANCER/TREATMENT/DRUGS

21. Ramucirumab (Mab to VEGFR-2)
USES: SECOND-LINE THERAPY
 Colorectal cancer (with FOLFIRI)
 Hepatocellular carcinoma (alone)
 Non-small cell lung cancer (with docetaxel)
 Also squamous NSCLC
 Erlotinib hydrochloride as first-line therapy in
mutations in the EGFR gene.
 Stomach adenocarcinoma or
gastroesophageal junction adenocarcinoma
(alone or with paclitaxel)
SPECIFIC SIDE EFFECTS
 Neutropenia
 Fatigue
 Stomatitis
 Diarrhea
 Worsening of Pre-existing Hepatic Impairment
 Thyroid Dysfunction
HTTPS://WWW.CANCER.GOV/ABOUT-CANCER/TREATMENT/DRUGS

22. Ziv-Aflibercept
HTTPS://WWW.CANCER.GOV/ABOUT-CANCER/TREATMENT/DRUGS
 Fusion protein
molecule
 traps VEGF-A, -B,
and PiGF
VEGFR-1 VEGFR-2

23. Ziv-Aflibercept
(fusion molecule, traps VEGF)
USES
Colorectal cancer
 with FOLFIRI regime
 leucovorin calcium (folinic acid),
 fluorouracil, and
 irinotecan hydrochloride
 Metastasized
 Cancer has not gotten better with other
chemotherapy.
RECOMBINANTLY PRODUCED
FUSION PROTEIN THAT
CAPTURES CIRCULATING
VEGF.
Specific side effects:
 Diarrhea
HTTPS://WWW.CANCER.GOV/ABOUT-CANCER/TREATMENT/DRUGS

24.  VEGF inhibitors doesn’t work
alone.It works wonders in
combination therapy.
 KEY POINTS FROM DR. KHILLAN
 Replaced byimmunotherapy.

25. Thank you
R E F E R E N C E : D E V I TA , H E L L M A N , A N D R O S E N B E R G ’ S C A N C E R : P R I N C I P L E S & P R A C T I C E O F O N C O LO G Y / [ E D I T E D B Y ]
V I N C E N T T. D E V I TA , J R . , T H E O D O R E S . L AW R E N C E , S T E V E N A . R O S E N B E R G . 1 1 T H E D I T I O N .