Targeting Cancer Pathways: The Tumor Microenvironment
Rakesh K. Jain, PhD (Harvard Medical School/MGH), and Padmanee Sharma, MD, PhD (MD Anderson Cancer Center)
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This webinar explores how the tumor microenvironment promotes oncogenic progression, while protecting the tumor from therapeutic intervention. By better understanding the tumor microenvironment we can develop strategies and treatment options to neutralize its oncogenic influence and more effectively attack the tumor itself. Topics covered include:
• The importance of understanding the tumor microenvironment and how it interacts with normal cells;
• What can be learned from the tumor microenvironment that might allow better, more effective therapeutics to be developed;
• How the abnormal microenvironment impacts anti-cancer drugs and how manipulating it with antiangiogenics can improve therapeutic outcomes.
Table of Contents
0:00 Welcome and overview
2:34 Rakesh Jain speaker profile
3:20 Reengineering the TME to enhance cancer treatment: bench to bedside to biomarkers
5:16 In vivo imaging of tumors
5:51 Blood vessels in glioblastoma
8:00 Impaired blood perfusion contributes to hypoxia and low pH
9:04 Interstitial fluid pressure in human tumors
9:37 Hypoxia and low pH fuel cancer hallmarks
11:08 Understanding impaired blood flow in tumors
12:45 Vascular normalization hypothesis
14:05 Cediranib treatment can increase tumor blood perfusion
14:54 Patients with increased perfusion survived ~9 months longer
15:47 Low dose anti-VEGFR2 treatment improves perfusion
19:10 Calculating tumor solid stress
20:23 Angiotensin-receptor blockers (ARBs) can deplete collagen I
21:30 Overall survival in patients treated with ARB/ACE-I
22:26 Vascular normalization can enhance immunotherapy
24:06 Summary
27:01 Padmanee Sharma speaker profile
27:32 Investigating immune responses to immune checkpoint therapies
27:53 T cells can adapt to antigenic changes, have specificity and memory
29:02 Tumor infiltrating lymphocytes correlate with clinical benefit in cancer patients
30:04 How can we drive T cells into tumors?
33:20 Complete responder: melanoma
34:36 Complete responder with anti-PD-1: metastatic renal cell cancer
35:08 Clinical activity in melanoma patients receiving ipilimumab and nivolumab
37:20 Pre-surgical clinical trial with anti-CTLA4 in patients with localized urothelial carcinoma
38:23 Power of pre-surgical trials: in-depth immune monitoring in matched tumors and blood samples
38:37 IHC demonstrating infiltrating T cells in prostate tumor tissues after immunotherapy
39:48 Increased frequency of ICOS+ T cells in tumors from anti-CTLA-4 treated patients
41:27 Targeting ICOS in combination with anti-CTLA-4 improves tumor rejection
43:13 Novel immunotherapy targets
43:27 Conclusions
44:35 Questions and answers
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