NCI, Prevention, and Screening

AACR Cancer Prevention Summit

February 3, 2016

Doug Lowy, M.D.

Acting Director, National Cancer Institute, NIH

Outline of

Presentation

Cancer mortality trends

NCI budget trends &

the cancer moonshot

Precision

medicine/oncology in

prevention & screening

Long-Term Mortality Trends 2002-2011, by Cancer Site

Percent Change 2002–2011

Men Women

3

Increasing Increasing

Decreasing Decreasing

Based on Kohler et al, Annual report to the nation on the status of cancer 1975-2011. JNCI, 2015

4

Competing RPG & NCI Total Obligations

FY 2012 FY 2013 FY 2014 FY 2015 Est.

Competing RPGs - Obligations 414,003,721 403,944,814 450,476,095 -

Competing RPGs - Count 1,085 1,095 1,207 -

NCI Total Obligations 5,067,341,795 4,789,014,389 4,932,368,225 4,953,028,000

-

1,000,000,000

2,000,000,000

3,000,000,000

4,000,000,000

5,000,000,000

6,000,000,000

-

100,000,000

200,000,000

300,000,000

400,000,000

500,000,000

600,000,000

700,000,000

800,000,000

Competing RPGs - Obligations NCI Total Obligations

Competing RPG Obligations NCI Total Obligations

508,126,000

1,236

Outlook for

Cancer

Research

Funding

Strong bipartisan support

in congress for NCI/NIH

Potential for continuing

increases in Federal

cancer research funding

Coordination with other

research efforts

The 2016 NCI Budget: A Substantial Increase After Many Years

of Flat Budgets & Decreasing Purchasing Power

6

NCI FY16

Appropriation

• ~$265 million total increase

• $70 million for the President’s

Precision Medicine Initiative in

Oncology (PMI-O)

• $195 million (must take

mandatory increases from this

number)

The Vice

President’s

Cancer Initiative

To accelerate progress in

cancer, including

prevention & screening

From cutting edge to

wider uptake of

standard of care

To encourage greater

cooperation and breaking

down silos

Within and between

academia,

government, and

private sector

Importance of data

sharing

Cancer Moonshot Federal Task Force: Feb 1, 2016

Cancer Moonshot Federal Task Force: Feb 1, 2016

Doug

Doug

14

Doug’s Definition of Precision Oncology

Interventions to prevent, diagnose, or treat cancer, based on a molecular and/or mechanistic understanding of the causes, pathogenesis, and/or pathology of the disease.

Where the individual characteristics of the patient are sufficiently distinct, interventions can be concentrated on those who will benefit, sparing expense and side effects for those who will not.

Oncogenic Microbial Agents are

Molecular Targets

Genes and proteins of oncogenic

microbial agents (such as HBV, HCV,

HPV, and EBV) are as much molecular

targets as B-raf, EGFR, etc.

Precision Oncology in Primary and

Secondary Prevention

The genetic and epigenetic changes in normal and premalignant tissues are less complex than in cancer

the driver changes may predominate in a higher proportion of premalignant lesions than of progressed lesions

Resistance is less likely to develop against interventions that target early changes

Premalignant cells are more stable genetically and less heterogeneous than cancer cells

Therefore, if you like targeted interventions for the treatment of cancer, you will love targeted interventions for prevention and screening of cancer

Cancer Screening: From Pattern

Recognition to Molecular Diagnosis

Precision oncology and its related technology have the potential to improve cancer screening

Primary screening tests for cervical cancer have gone from empiric pattern recognition (pap smear) to etiology-based (HPV) testing

Adegoke et al, J Womens Health 21:1031-37, 2012

Squamous cell: blacks

Squamous cell: whites

Adenocarcinoma: whites

Adenocarcinoma: blacks

Cervical cancer rates (USA): Decreasing

squamous cell cancer, stable

adenocarcinoma

Adenosquamous: blacks & whites

HPV testing can prevent more cervical cancers,

especially adenocarcinomas, than cytology

Ronco et al, Lancet 383: 524-33, 2014

Pooled cervical cancer incidence from 4 randomized controlled trials of

cytology (control arm) vs. HPV testing (experimental arm)

*Ratio of incidence with HPV testing vs. incidence with cytology

20

HPV testing: Ancillary molecular testing to

increase specificity (CIN2/3+)

HPV testing has high sensitivity but sub-optimal specificity (CIN2/3+)

Candidate ancillary molecular testing based on HPV-induced pathogenesis, to increase specificity

HPV induces p16INK4A and Ki-67 expression

Progression to CIN3+ is associated with methylation of silenced HPV genes

HPV Methylation for Triage of HPV-

positive women

0%

2%

10%

40%

100% Risk of precancer

Mirabello et al. JNCI 2012; Wentzensen et al. JNCI 2012; Clarke, Wentzensen et al. CEBP 2012

o HPV methylation can achieve risk stratification that alters clinical management

o Methylation testing can be done from the HPV DNA sample, is alos applicable for self-sampling

Methylation +

Methylation -

HPV +

HPV -

Population

Risk

Refer for culposcopy

23

Summary

An improved outlook for NCI/NIH appropriations

Precision oncology – broadly defined - represents a rational approach to cancer prevention, screening, and treatment

Precision oncology has the potential to improve outcomes in cancer prevention, screening, and treatment

www.cancer.gov www.cancer.gov/espanol