The pathophysiology of BTK in haematological malignancies is
characterised by its central role in aberrant BCR signalling that drives
malignant B-cell survival, proliferation, and resistance. The discovery and
development of BTK inhibitors have revolutionised the therapeutic approach to
these diseases by specifically targeting this key molecular node, disrupting the
pathological signalling cascades that sustain malignancy. BTK inhibitors can be
broadly categorised into covalent and reversible types based on their mode of
binding. Covalent inhibitors, such as ibrutinib, form an irreversible bond with
the cysteine residue (C481) in the BTK active site. This permanent attachment
prevents ATP binding and subsequent kinase activity, leading to durable
inhibition of BCR signalling. The clinical success of BTK inhibitors has
revolutionised the treatment of haematological malignancies, yet challenges
remain that drive ongoing research and innovation. One significant future
direction involves the development of next-generation BTK inhibitors designed
to overcome resistance and improve safety profiles. Combination therapies have
emerged as a crucial strategy to enhance the effectiveness of BTK inhibitors
and to overcome mechanisms of resistance. One of the most promising
combinations involves pairing BTK inhibitors with BCL-2 inhibitors such as
venetoclax.
Author(s) Details
Swati Shaileshkumar
Pawar
Arvind Gavali College of Pharmacy, Jaitapur, Satara,
Maharashtra, India.
Supriya Vikas Shinde
Arvind Gavali College of Pharmacy, Jaitapur, Satara, Maharashtra, India.
Divya Balu Bhagat
Arvind Gavali College of Pharmacy, Jaitapur, Satara, Maharashtra, India.
Shobha Hanumant
Pukale
Padmini College of Pharmacy, Dighanchi, Maharashtra, India.
Aishwarya Avinash
Patil
Dr. J.J.Magdum Pharmacy College, Jaysingpur, Maharashtra, India.
Please see the book here :- https://doi.org/10.9734/bpi/msup/v4/6406
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