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Molecular genetics, therapeutics and RET inhibitor resistance for medullary thyroid carcinoma and future perspectives - PubMed

Molecular genetics, therapeutics and RET inhibitor resistance for medullary thyroid carcinoma and future perspectives - PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/39342195/

Medullary thyroid carcinoma (MTC) is a rare type of thyroid malignancy that accounts for approximately 1-2% of all thyroid cancers (TCs). MTC include hereditary and sporadic cases, the former derived...

Medullary thyroid carcinoma management is evolving, with RET inhibitors improving outcomes, yet challenges remain in drug resistance and off-target effects, necessitating continued exploration of novel therapies and combinations.

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Recent progress in molecular classification of phaeochromocytoma and paraganglioma - PubMed

Recent progress in molecular classification of phaeochromocytoma and paraganglioma - PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/39271378/

Phaeochromocytomas (PC) and paragangliomas (PG) are neural crest cancers with high heritability. Recent advances in molecular profiling, including multi-omics and single cell genomics has identified up to seven distinct molecular...

Recent advances in molecular profiling reveal distinct subtypes of phaeochromocytomas and paragangliomas, aiding in prognostication, treatment stratification, and identification of therapeutic targets.

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Mechanisms of resistance to KRASG12C inhibitors in KRASG12C-mutated non-small cell lung cancer - PubMed

Mechanisms of resistance to KRASG12C inhibitors in KRASG12C-mutated non-small cell lung cancer - PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/39301544/

The KRAS protein, a product of the KRAS gene (V-ki-ras2 Kirsten rat sarcoma viral oncogene homolog), functions as a small GTPase that alternates between an active GTP-bound state (KRAS(ON)) and...

KRASG12C mutations drive lung adenocarcinoma, with sotorasib and adagrasib as first inhibitors. Resistance arises via on-target and off-target mechanisms, highlighting the need for further studies on genomic and non-genomic resistance.

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1yr

Did you know?  CAR-T cell therapy, a revolutionary cancer treatment, has achieved remission rates of over 80% in patients with certain types of leukemia. By genetically modifying a patient's own T cells to target cancer cells, this therapy offers hope for previously hard-to-treat cancers and is expanding into new indications.

Could CAR-T cell therapy become a mainstream treatment for various cancers, and what are the potential challenges to its broader application?

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Could CAR-T cell therapy become a mainstream treatment for various cancers, and what are the potential challenges to its broader application?

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1yr
The timeline of RET alterations in solid tumors

In 1985, Takahashi and colleagues cloned a novel oncogene from human T-cell lymphoma, naming it “rearranged during transfection” (RET), which is now known by its gene symbol RET. The oncogene was generated by recombining 2 unlinked DNA fragments during the transfection procedure.

Toward the end of that decade, researchers were able to show that RET encodes a receptor tyrosine kinase involved in fetal development of the hematopoietic, GI, nervous, and GU systems. Over the next several years, RET alterations via gene fusions and point mutations were identified as oncogenic drivers in papillary thyroid, medullary thyroid, NSCLC, colorectal, and breast cancers, among others.

Initial targeted therapy for RET-altered cancer consisted of multikinase inhibitors with RET inhibitory activity. At that time, treatment was limited by modest effectiveness and off-target adverse events, lending urgency to the development of RET-specific therapy.

Much work has been done since the 1980s and 1990s. Presently, certain selective RET inhibitors are approved for RET fusion–positive NSCLC and thyroid cancer as well as RET-mutated medullary thyroid cancer, and, in one case, can be tumor agnostic.

Have you used selective RET inhibitors in patients with RET-altered cancers? What are the benefits and challenges of these therapies?

  • 1yr
    I order it in all metastatic patients. I prefer RET testing as part of NGS.
  • 1yr
    Yes have used selpercatinib in lung and thyroid cancer with deep and durable responses, exceeding expectations with chemotherapy and much more tolerable

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