NCI, Prevention, and Screening

Transcription

1 NCI, Prevention, and Screening Doug Lowy, M.D. Acting Director, National Cancer Institute, NIH AACR Cancer Prevention Summit February 3, 2016

2 Outline of Presentation Cancer mortality trends NCI budget trends & the cancer moonshot Precision medicine/oncology in prevention & screening

3 Long-Term Mortality Trends , by Cancer Site Men Women Increasing Increasing Decreasing Decreasing Percent Change Based on Kohler et al, Annual report to the nation on the status of cancer JNCI,

4 Competing RPG & NCI Total Obligations Competing RPG Obligations 800,000,000 NCI Total Obligations 6,000,000, ,000,000 5,000,000, ,000, ,000,000 4,000,000, ,000,000 3,000,000, ,000,000 2,000,000, ,000, ,000,000 1,000,000,000 - FY 2012 FY 2013 FY 2014 FY 2015 Est. Competing RPGs - Obligations 414,003, ,944, ,476, ,126,000 - Competing RPGs - Count 1,085 1,095 1,207 1,236 - NCI Total Obligations 5,067,341,795 4,789,014,389 4,932,368,225 4,953,028,000 Competing RPGs - Obligations NCI Total Obligations - 4

5 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

6 The 2016 NCI Budget: A Substantial Increase After Many Years of Flat Budgets & Decreasing Purchasing Power 6

7 ~$265 million total increase NCI FY16 Appropriation $70 million for the President s Precision Medicine Initiative in Oncology (PMI-O) $195 million (must take mandatory increases from this number)

8 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

9 Cancer Moonshot Federal Task Force: Feb 1, 2016

10 Doug Cancer Moonshot Federal Task Force: Feb 1, 2016

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12 Doug

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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. 14

15 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.

16 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

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18 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

19 Cervical cancer rates (USA): Decreasing squamous cell cancer, stable adenocarcinoma Squamous cell: blacks Squamous cell: whites Adenocarcinoma: whites Adenocarcinoma: blacks Adenosquamous: blacks & whites Adegoke et al, J Womens Health 21: , 2012

20 HPV testing can prevent more cervical cancers, especially adenocarcinomas, than cytology *Ratio of incidence with HPV testing vs. incidence with cytology Pooled cervical cancer incidence from 4 randomized controlled trials of cytology (control arm) vs. HPV testing (experimental arm) Ronco et al, Lancet 383: ,

21 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 p16 INK4A and Ki-67 expression Progression to CIN3+ is associated with methylation of silenced HPV genes

22 HPV Methylation for Triage of HPVpositive women 100% Risk of precancer 40% Methylation + 10% Refer for culposcopy HPV + Methylation - Population Risk HPV - 2% 0% 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 Mirabello et al. JNCI 2012; Wentzensen et al. JNCI 2012; Clarke, Wentzensen et al. CEBP 2012

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 23

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