Cancer reasearch
Pro Research Analysisby 
Searched over 200M research papers for "cancer reasearch"
Consensus Meter
Advances in Cancer Research: Focus on RET-Altered Cancers and Therapeutic Strategies
RET-Altered Cancers: An Overview
RET (Rearranged during Transfection) alterations are significant oncogenic drivers in various cancers, including non-small-cell lung cancer (NSCLC) and thyroid cancer. These alterations can occur through gene fusions or point mutations, leading to the activation of the RET kinase, which promotes cancer cell proliferation and survival .
Multikinase Inhibitors and Their Limitations
Multikinase inhibitors (MKIs) such as cabozantinib and vandetanib have been explored for treating RET-altered cancers. However, their clinical efficacy has been modest, primarily due to off-target effects that result in significant toxicities, including hypertension, rash, and diarrhea . The response rates to these MKIs in patients with RET-rearranged NSCLC have been limited, with partial or complete response rates of 37% for cabozantinib, 18% for vandetanib, and 22% for sunitinib .
Emergence of Selective RET Inhibitors
The development of highly selective RET inhibitors such as selpercatinib and pralsetinib has marked a significant advancement in the treatment of RET-altered cancers. These inhibitors demonstrate improved efficacy and a more favorable toxicity profile compared to MKIs. Early-phase clinical trials have shown objective response rates of 68% with LOXO-292 (selpercatinib) and 50% with BLU-667 (pralsetinib), significantly surpassing the outcomes achieved with MKIs .
Immunotherapy and RET-Rearranged Lung Cancers
The role of immunotherapy in RET-rearranged lung cancers remains underexplored. While immune checkpoint inhibitors have been approved for various stages of NSCLC, their efficacy in RET-rearranged cases is not well characterized. Factors such as programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) are crucial in determining the benefit from immune checkpoint blockade, but their relevance in RET-rearranged lung cancers needs further investigation.
Physical Traits of Tumors and Treatment Resistance
The physical properties of tumors, including solid stress, interstitial fluid pressure, stiffness, and altered microarchitecture, play a critical role in cancer progression and treatment resistance. These physical traits can impair drug delivery, promote tumor invasiveness, and contribute to immune evasion. Understanding these biomechanical abnormalities is essential for developing new therapeutic strategies that can overcome these barriers.
Psychosocial Interventions for Cancer Survivors
Fear of cancer recurrence (FCR) is a prevalent and distressing issue among cancer survivors. Interventions like ConquerFear, which focus on attention training, metacognitions, acceptance/mindfulness, and values-based goal setting, have shown significant efficacy in reducing FCR and improving mental quality of life. These interventions are crucial for addressing the psychological needs of cancer survivors and improving their overall well-being .
Conclusion
The landscape of cancer treatment, particularly for RET-altered cancers, is rapidly evolving with the advent of selective RET inhibitors that offer improved efficacy and reduced toxicity. While multikinase inhibitors have provided some benefit, their limitations highlight the need for more targeted therapies. Additionally, understanding the physical traits of tumors and addressing the psychosocial aspects of cancer survivorship are essential components of comprehensive cancer care. Continued research and clinical trials will be pivotal in refining these therapeutic strategies and improving outcomes for cancer patients.
Sources and full results
Most relevant research papers on this topic