This document discusses advances in cancer diagnosis and treatment. It covers new diagnostic techniques like advanced pathology using techniques like IHC, FISH, and genomic assays that provide more molecular information about tumors. Imaging techniques like PET scans are now able to more precisely define tumors and monitor treatment response. The document also discusses the shifting treatment paradigm towards personalized and targeted therapies that act on specific molecular pathways identified as disrupted in a patient's cancer. Several new targeted drugs approved in recent years are mentioned along with the biomarkers they target like HER2, BCR-ABL, MEK, PI3K, VEGF receptors.

1. Advances in Diagnosis & Imaging
of Cancer- Impacting Treatment
Dr.Harsha Doddihal
Associate Medical Director-Quintiles,
Clinical Oncologist-My Health World,Indiranagar

2. Learning Objectives
 Treatment pillars of cancer
 Basics
 Advances in diagnosis
 Shifting paradigm
 New molecules approved and their rationale
•How does chemotherapy act? Name a tumor suppressor gene?
•When is surgery alone sufficient?
•What are the pathways mutated in a cancer cell?
•Knowing that it is a Non Small Cell Lung Cancer adenocarcinoma
sufficient?
•When is PET scan useful?
•How is new drug development and approval being shaped by molecular
advancements?

3. Management Of Cancer
Treatment, Diagnosis
CANCER
Surgery
PATHOLOGY &
IMAGING
Radiotherapy
Chemotherapy
Personalized/Molec
ular/Targeted

4. Cancer-MalignancyNeoplasm
Resisting Cell Death
Sustaining
Proliferative
Signaling
Evading growth
suppressors
Activating Invasion
and metastasis
Enabling replicative
immortality
Inducing
Angiogenesis
Hallmarks of Cancer-D Hanahan
2011

6. Shifting Paradigm-Pathology
 Cytology







FNAC
Incisional Biopsy
Excisional Biospy
Trucut Biposy
Surgical Specimen
Frozen Sample
Paraffin Block
CTC, CDNA
Exception: Brain and Bone
HPR
IHC
FISH
Oncotype DX
70, 21 Gene Assay
EGFR & ALK
CD 20
Kras
BCR-ABL, Philadelphia
Chromosome
ER/PgR
HER 2
BRAF
PSA
CA125
CA19 9
AFP
βHCG

7. Advances In Diagnosis

8. Tumor definition by PET
Vander wel et al. Int J Radiat
Oncol Biol Phys. 2005; 61: 649-55.

9. Response to Hormonal Therapy
Post-Rx
Pre-Rx
Example 1
• Recurrent sternal
lesion
• ER+ primary
• Recurrent Dz
strongly FES+
Example 2
FES
FDG
FDG
• Newly Dx’d met
breast CA
• ER+ primary
• FES-negative
bone mets
University of Washington
(Linden, J Clin Onc, 2006)

10. Key advances in the history of cancer
chemotherapy.
DeVita V T , and Chu E Cancer Res 2008;68:8643-8653
©2008 by American Association for Cancer Research

11. Key advances in the history of cancer
chemotherapy.
DeVita V T , and Chu E Cancer Res 2008;68:8643-8653
©2008 by American Association for Cancer Research

12. Cancer genomics: from discovery science to
personalized medicine Nature
Medicine 17, 297–303 (2011)

13. Targeted Therapy Definition
 Drugs targeted at pathways, processes and physiology
which are uniquely disrupted in cancer cells:
 Receptors
 Genes
 Angiogenesis
 Tumor pH

14. Hormonal Therapy-Breast Cancer
Anastrozole,
Letrozole

15. CML
Mechanism of action of imatinib
Bcr-Abl
P
P
P
Bcr-Abl
Substrate
Substrate
Y
ATP
Imatinib
P
Y=
Tyrosine
P=
Phosphat
e
Nilotinib
Dasatinib
Ponatinib

16. Bevacizumab

17. HER 2
http://www.gene.com/media/product-information/kadcyla-moa

20. Molecule
Compan
y
Target
Indication
Other
Indication
s
Gazyva
(obinutuzumab)
Genentec
h
CD 20
Untreated CLL
Gilotrif (afatinib)
BI
ErbB1, ErbB2,
ErbB4
mNSCLC
Imbruvica (ibrutinib)
Pharmacy Bruton’s tyrosine
clics
kinase BTK
Mantle cell
Lymphoma
Kadcyla (adotrastuzumab
emtansine)
Genentec
h
Her-2
MBC
Mekinist (trametinib)
GSK
MEK 1 & 2
M Melanoma
BRAF
V600E/K
Pomalyst
(pomalidomide)
Celgene
Immunomodulatory
RRMM
Revlimid (lenalidomide) Celgene
Immunomodulatory
Mantle Cell
MM, MDS
Stivarga (regorafenib)
Bayer
VEGF, Multikinase
Inhibitor
Advanced
GIST
mCRC,
AMD
Tafinlar (dabrafenib)
GSK
BRAF kinases
M Melanoma

21. Thank you
Questions???
Dr.Harsha Doddihal,
Curate’s Egg!
Associate Medical Director, Quintiles,
Consultant Oncologist- My Health World,
Indiranagar