Therapeutic Implications of FGFR in Solid Tumor Therapy

Dr. Niti Raizada

MD DNB DM ECMO MRCP(UK)
Director, Medical Oncology & HematoOncology,
Fortis Group of Hospitals, Bangalore

The therapeutic implication of FGFR in solid tumor therapy have been numerous. In the era of Precision Oncology and also with the technological advancement of Next Generation Sequencing many targetable novel biomarkers are getting discovered. These biomarkers with multiple genetic alterations contribute significantly to the development of different cancers in humans.

FGFR is one such Biomarker whose altered genetic sequence gives rise to some cancers in humans. FGFR stands for Fibroblast Growth Factor Receptor, secreted from cells has a role in wound healing meaning it contributes significantly to cell proliferation and cell growth.

Cancer is the name given to a collection of related diseases. In all types of cancer, some of the body’s cells begin to divide without stopping and spread into surrounding tissues (Metastatic). Cancer can start almost anywhere in the human body when there is an abnormal change in the normal DNA sequence that codes for specific functional proteins.

Genomic Alterations in FGFR initiate the process of Carcinogenesis in different parts of our body that includes, Breast, Bile Duct, Urinary Bladder, Lung, etc. There are Point Mutations, Gene Amplifications, Activating Mutations, and Gene Fusions which are associated with FGFR related human cancers. FGFR altered cancer is very hard to treat as there are very limited targetable drugs available and most of them show resistance after a certain period.

The first-ever drug that has been approved by FDA is Erdafitinib for metastatic locally advance Urothelial malignancy, which is a Tyrosine Kinase Inhibitor. Cholangiocarcinoma, the cancer of the bile duct, considered to be rare and deadly, harbors 20% of FGFR2 fusions. FDA has approved Pemigatinib and Infigratinib respectively for the treatment of the patient who is having FGFR2 fusion-related Cholangiocarcinoma.

FGFR is proving itself as a potential PAN-Cancer marker as it contributes significantly to the process of carcinogenesis in different malignancies. Tyrosine kinase domain and Gene fusion of FGFR is the target of choice for different pharmaceutical companies and clinical researchers.

FDA grants breakthrough therapy designation for Futibatinib for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene rearrangements, including gene fusions. With the three FDA-approved drugs that target FGFR altered tumors FGFR has become “Undruggable to Druggable” in recent years.

Many ongoing trials are showing promise in the treatment of FGFR altered cancers in humans. And the day is not far when there will be adequate targetable drugs available for the treatment of FGFR altered cancers.