Dr.Harsha Doddihal

Associate Medical Director-Quintiles,

Clinical Oncologist-My Health World,Indiranagar

Advances in Diagnosis & Imaging

of Cancer- Impacting Treatment

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?

Management Of Cancer Treatment, Diagnosis

CANCER

Surgery Radiotherapy Chemotherapy Personalized/Molec

ular/Targeted

PATHOLOGY &

IMAGING

Cancer-Malignancy-

Neoplasm

Resisting Cell Death

Sustaining

Proliferative

Signaling

Evading growth

suppressors

Activating Invasion

and metastasis

Enabling replicative

immortality

Inducing

Angiogenesis

Hallmarks of Cancer-D Hanahan

2011

Shifting Paradigm-Pathology

Cytology

FNAC

Incisional Biopsy

Excisional Biospy

Trucut Biposy

Surgical Specimen

Frozen Sample

Paraffin Block

CTC, CDNA

HPR

IHC

FISH

Oncotype DX

70, 21 Gene Assay

EGFR & ALK

CD 20

Kras

BCR-ABL, Philadelphia

Chromosome

ER/PgR

HER 2

BRAF

Exception: Brain and Bone

PSA

CA125

CA19 9

AFP

βHCG

Advances In Diagnosis

Tumor definition by PET

Vander wel et al. Int J Radiat

Oncol Biol Phys. 2005; 61: 649-55.

Response to Hormonal Therapy Pre-Rx Post-Rx

FES FDG FDG

• Newly Dx’d met

breast CA

• ER+ primary

• FES-negative

bone mets

University of Washington

• Recurrent sternal

lesion

• ER+ primary

• Recurrent Dz

strongly FES+

Example 1

Example 2

(Linden, J Clin Onc, 2006)

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

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

Cancer genomics: from discovery science to

personalized medicine Nature

Medicine 17, 297–303 (2011)

Targeted Therapy Definition

Drugs targeted at pathways, processes and physiology

which are uniquely disrupted in cancer cells:

Receptors

Genes

Angiogenesis

Tumor pH

Hormonal Therapy-Breast Cancer

Anastrozole,

Letrozole

CML

Substrate

Imatinib

Bcr-Abl

Y =

Tyrosine

P =

Phosphat

e

Bcr-Abl

ATP

Substrate

P P P

P

Y

Mechanism of action of imatinib

Nilotinib

Dasatinib

Ponatinib

Bevacizumab

HER 2

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

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

clics

Bruton’s tyrosine

kinase BTK

Mantle cell

Lymphoma

Kadcyla (ado-

trastuzumab

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

Valchlor Ceptaris Alkylating agents Mycosis

Thank you

Questions???

Curate’s Egg!

Dr.Harsha Doddihal,

Associate Medical Director, Quintiles,

Consultant Oncologist- My Health World,

Indiranagar