VEGF Targeted Therapies Overview

Study Notes

Different approaches for targeting VEGF include monoclonal antibodies (e.g., bevacizumab) and Receptor Tyrosine Kinase Inhibitors (e.g., sorafenib).
Monoclonal antibodies, like bevacizumab (Avastin), target and neutralize specific VEGF isoforms, preventing their interaction with VEGF receptors.
Bevacizumab is FDA-approved for certain cancers, including metastatic colorectal cancer, non-small-cell lung cancer, metastatic renal cell carcinoma, and others.

Bevacizumab prevents VEGF from binding to its receptors, interrupting the signaling pathway that promotes angiogenesis.
VEGF Trap is another method that inhibits VEGF.

Cardiovascular effects, such as hypertension, are a possible result of VEGF inhibition.
VEGF's role in EC-platelet homeostasis can also be disrupted, potentially leading to thromboembolic events (such as arterial problems).
VEGF is also crucial for maintaining cardiomyocyte survival and glomerular podocyte function. Disrupting VEGF signaling can affect these important structures..
VEGF blockade may affect wound healing, and other treatment areas can produce further issues in patients undergoing surgery.

Sorafenib (Nexavar) is a multi-targeted RTKI that inhibits multiple kinases, including VEGFRs, Raf, and PDGFR, and is licensed for advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC).
Axitinib (Inlyta) is a more selective VEGFR2 inhibitor, approved for second-line RCC treatment when other RTKIs like sunitinib fail.

Studies show variations in the incidence and severity of hypertension based on the specific anti-VEGF therapy used.

Tumors can develop mechanisms to evade anti-VEGF therapies. These include increased angiogenesis via pathways other than VEGF, and/or resistance by other factors such as tumour vessels covered in pericytes, and bone marrow/cellular rescue.

HER2 is a receptor tyrosine kinase that when over-expressed, can promote rapid cell growth and has clinical implications in various cancers, including breast cancer.
Monoclonal antibodies, like trastuzumab (Herceptin), are used to target HER2 proteins on cells.
Trastuzumab can induce remission in certain HER2-positive breast cancers, but concerns include resistance and potential cardiac toxicity.

Tamoxifen is a selective estrogen receptor modulator, used to inhibit estrogen's stimulatory effect on breast cancer cells.
It has been used in post-menopausal breast cancer treatment and shows clinical benefit in combination or alone with cytotoxic agents for sustained treatment periods of 5 years.
Tamoxifen can have side effects like hot flashes, nausea, and mood swings and can increase the risk of endometrial cancer if used long-term.

HPV vaccines (Gardasil and Cervarix) can help prevent cervical cancer.
Various HPV strains exist; some are more cancerous than others
Vaccines are preventative; the vaccine does not treat HPV or infections related to to this virus.
Vaccines may show short-term protection and long term follow up study may be required. Additional treatment approaches for individuals may be required if already exposed to HPV.

CAR-T cell therapy involves engineering a patient's T cells to target cancer-specific antigens.
Highly complex; has great potential results but requires close monitoring and careful selection of patients, similar to some of the other complex treatment approaches.