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Rare cancers narrowed by another “inib”: clinical trial warrants hope for neuroendocrine tumors

More than 12,000 people in the United States are diagnosed with a neuroendocrine tumor each year. The tumors begin in neuroendocrine cells – which have characteristics of nerve and hormone-producing cells – and can arise in multiple sites in the body, most often in the gastrointestinal tract, lungs and pancreas. Treatments may include surgery, targeted therapy, peptide receptor radionuclide therapy, chemotherapy or other local treatment approaches depending on the location and stage of the cancer. For patients whose cancer continues to grow and spread after these treatments, better options are urgently needed. A drug that simultaneously strikes cancer cells’ growth circuits and pipeline to the bloodstream produced encouraging results in a clinical trial involving patients with advanced neuroendocrine tumors, according to a study led by Dana-Farber Cancer Institute investigators.

Patients treated with the drug, cabozantinib, survived significantly longer with no worsening of their disease than patients who received a placebo. According to scientists, the results suggest cabozantinib, which has been approved by the U.S. FDA for some patients with renal cell carcinoma, thyroid cancer or liver cancer, can benefit patients with neuroendocrine tumors that continue to grow and spread after previous therapies. Cabozantinib undermines tumor cells in multiple ways. It blocks the receptor for VEGF, a growth factor needed to build new blood vessels and to supply oxygen to cells and tissues, even cancers. Cabozantinib targets other receptors as well as, including c-MET, c-AXL and c-RET that are key to tumor cell survival and metastasis. The study enrolled 93 patients with pancreatic neuroendocrine tumors and 197 patients with advanced neuroendocrine tumors outside the pancreas.

Two-thirds of the participants were randomly assigned take a 60 mg cabozantinib pill daily, and the others were given a placebo. Researchers measured progression-free survival (PFS) – how long patients lived before their disease worsened – for all participants. At a median follow-up of 13.9 months, the PFS for patients with extra-pancreatic tumors who took cabozantinib was 8.3 months, compared to 3.2 for those who took a placebo. At a median follow-up of 16.7 months, patients with pancreatic tumors who took cabozantinib had a PFS of 11.4 months, compared to 3 months for those who took a placebo. Side effects of cabozantinib were similar to those found in other studies of the drug and included fatigue, diarrhea, hypertension and skin rash. This is another example to a phenomenon similar to “drug repurposing”, where a drug with an original target is discovered to possess additional organic or molecular targets.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Cella CA et al. Endocr Relat Cancer. 2023 Oct; 30(12):e230232.

Baudry E, Naoun N et al. Eur J Cancer. 2023 Nov; 193:113292.

Corti F, Brizzi MP et al. BMC Cancer. 2023 Sep 26; 23(1):908.

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Dott. Gianfrancesco Cormaci
Dott. Gianfrancesco Cormaci
Laurea in Medicina e Chirurgia nel 1998, specialista in Biochimica Clinica dal 2002, ha conseguito dottorato in Neurobiologia nel 2006. Ex-ricercatore, ha trascorso 5 anni negli USA alle dipendenze dell' NIH/NIDA e poi della Johns Hopkins University. Guardia medica presso la casa di Cura Sant'Agata a Catania. In libera professione, si occupa di Medicina Preventiva personalizzata e intolleranze alimentari. Detentore di un brevetto per la fabbricazione di sfarinati gluten-free a partire da regolare farina di grano. Responsabile della sezione R&D della CoFood s.r.l. per la ricerca e sviluppo di nuovi prodotti alimentari, inclusi quelli a fini medici speciali.

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