Medical Oncologist
Targeted therapy
RET Fusion Cancer: — Lung, Thyroid and Targeted Treatment
RET fusions are genetic changes that can be targeted with a specific class of medicines called RET-selective kinase inhibitors. If testing confirms a RET fusion in your tumour, treatment options are different — and more precise — than standard chemotherapy.
Medically reviewed by Dr. C. Raghavendra Reddy, Medical Oncologist, MBBS (Gold Medal) · DNB · DM (Medical Oncology, Gold Medal) · Last reviewed August 2026
- A targetable driver — RET fusions activate a protein that drives cancer growth, and RET-selective medicines are designed to block it directly.
- Testing comes first — A molecular test on your tumour tissue is needed to confirm a RET fusion before a targeted medicine can be recommended.
- Oral daily tablets — RET-selective inhibitors are taken as tablets at home, not given by infusion in a clinic.
- Lung and thyroid, mainly — RET fusions are most common in certain lung and thyroid cancers, though they can appear in other tumour types.
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RET fusions are genetic rearrangements that drive cancer growth in a subset of lung and thyroid cancers. A class of medicines called RET-selective kinase inhibitors — including selpercatinib and pralsetinib — are designed to block this driver directly. NCCN and ESMO both recommend testing for RET fusions before starting systemic treatment for non-small-cell lung cancer.
What is a RET fusion and how does it drive cancer?
A RET fusion happens when the RET gene breaks off from its normal position in a chromosome and joins with another gene. The joined pair produces an abnormal protein that stays permanently switched on, telling cells to keep dividing without stopping.
RET fusions are found in a proportion of non-small-cell lung cancers and in a meaningful share of papillary thyroid cancers, according to NCCN and ESMO guidance. They also appear in smaller numbers of colorectal, pancreatic, and other tumour types.
Because the fusion protein is the driver, medicines that block it can stop tumour growth more precisely than chemotherapy, which affects all rapidly dividing cells whether cancerous or not.
Which medicines target RET fusions?
Two RET-selective kinase inhibitors are recommended by NCCN and ESMO for RET fusion-positive cancers: selpercatinib and pralsetinib. Both are taken as oral tablets at home rather than given by infusion.
Selpercatinib is indicated for RET fusion-positive non-small-cell lung cancer and for RET fusion-positive or RET-mutant thyroid cancers. Pralsetinib carries similar indications for lung and thyroid cancer. Trial data presented at ASCO and ESMO show that a proportion of patients achieve meaningful tumour reduction with both medicines.
Older medicines called multikinase inhibitors — including cabozantinib and vandetanib — also affect RET but are less selective. They remain options for medullary thyroid cancer in situations where the newer selective inhibitors are not available or not indicated.
Your oncologist will confirm which medicine is appropriate based on your cancer type, biomarker results, and drug access in India. CDSCO approval status and local formulary availability will shape the specific recommendation you receive.
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Dr. C. Raghavendra Reddy
MBBS(Gold Medal), DNB(General Medicine), DM(Medical Oncology)(Gold Medal)
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MBBS, MD(General Medicine), DM(Medical Oncology)(Adyar,Chennai), ECMO, MRCP SCE(UK)
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MBBS, MD (General Medicine), DrNB (Medical Oncology), ECMO, MRCP SCE (Medical Oncology) (UK)
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What side effects do RET inhibitors cause?
The most commonly reported side effects of selpercatinib and pralsetinib include raised liver enzymes, raised blood pressure, fatigue, dry mouth, and swelling in the legs or feet. Most are manageable and do not require stopping treatment.
Your team will monitor your liver function and blood pressure regularly, particularly in the first few months. Dose adjustments are sometimes made to manage side effects while keeping treatment going.
Tell your team straight away if you notice yellowing of the skin or eyes, a significant new swelling, or any new breathing difficulty. These are less common but need prompt assessment.
What should I ask my oncologist before starting a RET inhibitor?
- Whether your biopsy sample has been sent for molecular testing, including RNA-based fusion testing — RNA picks up more fusion types than DNA testing alone
- Which RET inhibitor your centre recommends and whether it is available locally or requires access through a patient support programme
- What your baseline blood pressure and liver function results show, since both are monitored closely during treatment
- Every medicine, supplement, or herbal preparation you are currently taking — interactions are possible with RET inhibitors
- Whether you are pregnant, planning pregnancy, or breastfeeding — these medicines carry risks that need to be discussed
- How often you will need blood tests and clinic reviews after starting
What happens between diagnosis and starting targeted treatment?
Molecular testing is ordered
Your oncologist sends your biopsy tissue to a molecular pathology laboratory for next-generation sequencing or a targeted fusion assay. RNA-based testing is preferred where available, as it detects a broader range of fusion partners than DNA testing alone.
Results are reviewed
Results typically take one to three weeks. Your oncologist confirms whether a RET fusion is present and explains what it means for your treatment options.
Treatment is planned
If a RET fusion is confirmed and a targeted inhibitor is indicated for your cancer type and stage, your oncologist discusses the specific medicine, its goals, and what to monitor during treatment.
Drug access is arranged
Your team confirms availability, insurance coverage, and any patient support or compassionate access programmes offered by the manufacturer.
You start treatment and attend follow-up
You take the tablet daily at home. Regular blood tests and clinic visits are scheduled to monitor response and check for side effects, particularly liver function and blood pressure.
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Common questions
Frequently asked questions
What test confirms a RET fusion?
Next-generation sequencing (NGS) of your tumour tissue is the most comprehensive test. RNA-based sequencing picks up more fusion types than DNA-based testing alone, and NCCN guidance recommends it for non-small-cell lung cancer. If your original biopsy sample is too small, a repeat biopsy or a liquid biopsy from a blood sample may be an option. Ask your oncologist whether RNA-based testing was included and, if not, whether it should be done.
Are selpercatinib and pralsetinib available in India?
Availability varies by centre, city, and insurance plan. Selpercatinib has received regulatory approval in India through CDSCO, and manufacturer patient support programmes exist in some settings. Pralsetinib's availability may differ. Your oncologist or a dedicated oncology pharmacist at your centre is the best person to confirm what can be accessed for you, including any compassionate use or assistance pathways. Do not assume availability — confirm it specifically before planning treatment.
How long does RET-targeted treatment continue?
In most cases, RET inhibitors are continued for as long as the cancer responds and side effects are manageable. There is currently no fixed endpoint, unlike a defined number of chemotherapy cycles. Your oncologist will monitor your response through scans at regular intervals and will discuss any changes to the plan if the cancer begins to grow again or if side effects require adjustment.
What happens if the cancer stops responding to a RET inhibitor?
Resistance to RET inhibitors can develop over time. When that happens, your oncologist may arrange repeat molecular testing on a new biopsy or blood sample to look for the mechanism of resistance. Some patients can switch to a different RET inhibitor or enrol in a clinical trial. NCCN and ESMO guidance on resistance is evolving, and your oncologist will discuss what is appropriate for your specific situation at that point.
Do RET fusions run in families?
RET fusions in lung cancer are almost always acquired changes that occur in the tumour tissue — they are not inherited and do not increase risk for your relatives. The situation is different for RET mutations in medullary thyroid cancer, where inherited forms exist and family screening may be recommended. If your cancer is a medullary thyroid cancer or your oncologist suspects a hereditary cause, genetic counselling will be discussed with you separately.
Can I take my usual medicines alongside a RET inhibitor?
Some medicines interact with RET inhibitors, including common ones for blood pressure, acid reflux, and infections. Herbal preparations and supplements can also interact. Bring a complete list of everything you take — including over-the-counter medicines and supplements — to your appointment before starting. Do not stop or adjust any current medicine without speaking to your oncologist first, as some interactions need a managed plan rather than a simple stop.