Ongoing Cancer Research: School of Public Health and Health - - PowerPoint PPT Presentation

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Ongoing Cancer Research: School of Public Health and Health - - PowerPoint PPT Presentation

Dec 27, 2022 45 likes •416 views

Ongoing Cancer Research: School of Public Health and Health Professions Jean W actaw ski-W ende, PhD Dean, School of Public Health and Health Professions SUNY Distinguished Professor Monday, February 1 6 , 2 0 1 6 UB Council Meeting Cancer

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Ongoing Cancer Research: School of Public Health and Health Professions

Jean W actaw ski-W ende, PhD Dean, School of Public Health and Health Professions SUNY Distinguished Professor Monday, February 1 6 , 2 0 1 6 UB Council Meeting

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Cancer is a national priority

 Obama “Cancer Moonshot” (Targeting treatments, screening and prevention)  Cuomo NYS funding to Screen/ Treat Cancer  2016 estimates:

 1.69 million new cancer cases in the US (110K NYS)  596,000 deaths (35K NYS)

 US lifetime risk: 1 in 3 women; 1 in 2 men

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Public Health

  • Focus on disease occurrence in larger populations and groups
  • Prevention focused
  • Research on risk factors for disease; Prevention trials
  • Mechanistic studies (clinical translational)
  • At UB SPHHP, w e have a trem endous am ount of ongoing

w ork in cancer

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W om en’s Health I nitiative

1 9 9 3 – present ( now thru 2 0 2 0 …) A 12 year (now 22+ ) study of the major causes of disease and death in postmenopausal women.

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2 Horm one Therapy Trials: Coronary Heart Disease & Fractures Adverse effect for Breast Cancer? Calcium / Vitam in D Trial: Fractures & Colorectal Cancer Dietary Modification Trial: Breast & Colorectal Cancers & Coronary Heart Disease

9 3 ,6 7 6

Observational Study

4 8 ,8 3 5 3 6 ,2 8 2

3 Controlled Trials

6 8 ,1 3 5

1 Observational Study

2 7 ,3 4 7

1 6 1 ,8 0 8 w om en total

W om en’s Health I nitiative

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WHI Clinical Centers (40)

Seattle Portland Sacramento Reno Oakland Stanford Los Angeles Orange Torrance Honolulu San Diego Tucson San Antonio Houston Gainesville Miami Birmingham Atlanta Memphis Chapel Hill Winston-Salem Washington, DC Cincinnati Columbus Pittsburgh Newark Stony Brook Pawtucket Boston Worcester Bronx Buffalo Detroit Minneapolis Milwaukee Madison Iowa CityChicago Pool 1 Clinical Centers (30) Minority Clinical Centers (10)

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26% Increase Breast Cancer

34% (Hip) Fracture Reduction

STOPPED Early, Harm Threshold Level 29% Increase CHD 44% Increase Ischemic Stroke

Risks Benefits

113% Increase Pulmonary Emboli

44% Fewer Colorectal Cancers (but more aggressive)

Balance of Risks & Benefits:

The WHI E+P Trial, 2002

(Mean Follow-up = 5.6 yrs)

JAMA, 2002

Endometrial Cancer

Death

No Effect

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Total Prescriptions Dispensed for Combination Estrogen/Progestin Products, 1995 - July 2003

5000 10000 15000 20000 25000 1995 1996 1997 1998 1999 2000 2001 2002 YTD July 2003 Year TRX (000) PREMPRO PREMPHASE PREMPRO LOW DOSE FEMHRT ACTIVELLA PREFEST COMBIPATCH IMS Health, National Prescription Audit Plus™, 1995 – July 2003, extracted August 2003.

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Public Health Impact…

  • ne example
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Clinical Trial: CEE+ MPA vs. Placebo Breast Cancer Risk During I ntervention and Postintervention

Chlebowski RT, Kuller L, Prentice R, et al. N Engl J Med 360;6:11-25

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Economic and Public Health Impact… … another example

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Econom ic and Health I m pact of the W HI Estrogen+ Progestin Trial

Roth et al, Annals of I nternal Medicine, May 2 0 1 4

Trial cost $260 million (in 2012 dollars), produced a net economic return of $37.1 billion:

  • a return of $140 for every dollar invested in the trial.

Estimated health benefits (10 years following):

  • $4.3 million fewer women used HT from 2002-2012
  • Prevented (estimated in the following 10 years):
  • 126,000 fewer cases of breast cancer
  • 76,000 fewer cases of cardiovascular disease
  • 80,000 fewer cases of venous thromboembolism (VTE)
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Cancer Focus in W HI : Additional research

 Risk Factors:

 Diet, 2nd hand smoke, co-morbidities, medications, physical activity, race/ ethnicity…  Periodontal Disease – total cancer, lung, upper GI, breast

 Blood/ Tumor biomarkers:

 Telomeres, proteome, metabolome, genetics/ genomics (consortium)

 Hundreds of scientific papers, ancillary grants  Two national team science awards for this work

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Oral Microbiom e, Periodontal Disease

Oral bacteria Oral bacteria Gingivitis Gingivitis Periodontitis Periodontitis Bone and tissue destruction Bone and tissue destruction Tooth loss Tooth loss

Gingiva Alveolar bone Periodontal ligament Periodontal pocket Inflammation

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OsteoPerio 1 5 -Year Follow -up Feasibility Study:

Microbiom e Com position Differs by Periodontal Health/ Disease

Healthy Severe Periodontitis

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Cancer: Buffalo OsteoPerio Microbiom e Study

OsteoPerio Microbiome: Ongoing $4M NIH funded study (2014-2019) 1000 women, 15 years, 3 time points Bacterial composition in:

 Cancer Cases vs No Cancer  Tumor Blocks compared to Oral samples  Potential to develop new targeted interventions

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SPHHP Faculty Active in Cancer Research

R25 Training grant

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Thank you. Questions?

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Anti-cancer Approaches with PoP Nanoparticles

Jonathan Lovell Department of Biomedical Engineering February 15, 2015 UB council presentation

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  • Long circulating doxorubicin

“liposome” by J&J

  • Kaposi’s sarcoma, multiple

myeloma, metastatic ovarian, breast (off label)

  • Less cardio-toxic vs free drug
  • Poor drug bioavailability

DOXIL – the first “nanomedicine”

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Putting chlorophyll to work

PoP

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Spatial and temporal control of release

Carter al., Nature Communications, 2014

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Chemophototherapy

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Patient derived pancreatic tumors

Enhanced accumulation

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Luo et al., J Controlled Release, 2015

Enhanced distribution

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PoP-liposomes vs. photodynamic therapy PoP-liposomes vs. conventional chemo.

PDT Dox-PoP

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Dox-PoP-liposomes: Storage Stability

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Translational strategy for chemophototherapy

  • 1. Manufacture
  • 2. Stability/Sterility
  • 3. PK/tox
  • 4. Phase I/II trial
  • Local breast cancer recurrence
  • No anesthesia, easy irradiation
  • High prevalence
  • Dox used for breast
  • Other candidates: liver & brain via fibers.
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Local and metastatic cancer Targeted therapy

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Functionalization of Co PoP with tagged proteins

Shao et al., Nature Chemistry, 2015

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Cargo-loaded liposomes with a targeting ligand

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Summary

  • Light-activated PoP liposomes
  • New local tumor treatment
  • Higher drug deposition
  • Uniform drug distribution
  • Formulation finalized
  • Future directions: clinical manufacturing and trials
  • Targeted Cobalt PoP liposomes
  • Enabling technology for ligand attachment
  • Translatable screening platform for targeted delivery
  • Future directions: drug targeting; multivalent targeting
  • Future directions: vaccines
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Acknowledgements

Lab members Collaborators

POSTECH, Korea Chulhong Kim, PhD University of Wisconsin Weibo Cai, PhD McMaster University Joaquin Ortega PhD University of Waterloo Mikko Karttunen, PhD Roswell Park Cancer Institute Ravi Pandey, PhD

Funding

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Thank you!

j flovell@ buffalo.edu

Department of Biomedical Engineering