Cell signalling pathway in cancer, Their therapeutic implication

1. Cell SIGNALING
&
CELL DEATH
Dr KUNDAN
Surgical Oncologist
Mahavir Cancer Sansthan , Patna

7. Signal transduction pathway

9. RAS pathway
• Also known as RAS – RAF- MEK – ERK pathway
• RAS ( RAt Sarcoma ) - small family of GTPase
• Protonocogen
• > 150 Types has discovered till now
• H Ras ( Harvey RAS )
• K Ras ( Kristen RAS )
• N Ras ( Neuroblastoma Ras )
• 30 % of cancers are associated with RAS
mutations

10. • Oncological mutations are concentrated
within 2 hotspots (around codons 12 and 61)
of the primary nucleotide sequence of all ras
family members.
• K RAS Pancreatic / Colonic / Lung cancers
• N RAS Leukemia / Thyroid / Malignant
Melanoma
• H RAS – Bladder Tumor

17. • PI3K /AKT/mTOR pathways mutaions are associated
with
Ovarian Carcinoma
Breast Cancers
Urothelial Cancers
• PI3K inhibitors - PICTILISIB
BUPARLISIB
IDEALISIB
COPANLISIB
• AKT inhibitors- IPATASERTIB
• mTOR inhibitor – EVEROLIMUS

20. • Associated malignancy
Melanoma
Prostate Cancer
Breast Cancers
Lymphoma
Leukemia
JAK STAT inhibitors
Ruxolitinib
Tofacitinib

21. Apoptosis
• Greek word , meaning Falling off
• Pathway of cellular death
• Purpose – Elimination of unwanted cells
• It can be pathological / Physiological

22. Morphology of Apoptosis
• Cell shrinkage
• Chromatin
condensation
• Cytoplasmic Bleb
• Apoptotic bodies
• Phagocytosis

23. • Biochemical features
Protein cleavage – Hydrolysis by CASPASE
DNA Breakdown – Endonuclease
Phagocytotic Recognition

24. CASPASES
• Cystein Protease - ‘ASPASE ‘ - Cleave after
Aspartic acid residue

28. Evasion of Apoptosis
• Viable cell prevent their own engulfment by
expression of CD 31 molecule
• Anti Apoptotic molecule
BCL 2 , BCL X
• Pro-Apoptotic molecule
BAX , BIM , BAK