Publications by authors named "Ravi Velaga"

Article Synopsis
  • Neoadjuvant treatment with microtubule inhibitors (MTIs) for triple negative breast cancer (TNBC) is not well understood, prompting a study that analyzed tumor samples to correlate genetic mutations with treatment response.
  • The study found that tumors with high homologous recombination deficiency (HRD) and specific mutations (like BRCA2) had higher rates of complete response to MTIs like eribulin and paclitaxel.
  • Transcriptomic profiling highlighted FGFR2 downregulation as a critical gene linked to treatment response and identified a significant pathway (glycan degradation) that could influence resistance to these therapies in TNBC patients.*
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Breast and prostate cancers are generally considered immunologically 'cold' tumors due to multiple mechanisms rendering them unresponsive to immune checkpoint blockade therapies. With little success in garnering positive outcomes in modern immunotherapeutic clinical trials, it is prudent to re-examine the role of immunogenic neoantigens in these cold tumors. Gene fusions are driver mutations in hormone-driven cancers that can result in alternative mutation-specific neoantigens to promote immunotherapy sensitivity.

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Over the past two decades, high sensitivity to HER2-amplified primary breast cancers has been achieved with HER2-targeted therapies. CDK4/6 inhibitors have long been identified as a potential treatment option for advanced breast cancer patients. However, acquired HER2 heterogeneity leading to resistance during the treatment has been identified as a bottleneck.

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Female breast cancer emerged as the leading cancer type in terms of incidence globally in 2020. Although mortality due to breast cancer has improved during the past three decades in many countries, this trend has reversed in women less than 40 years since the past decade. From the biological standpoint, there is consensus among experts regarding the clinically relevant definition of breast cancer in young women (BCYW), with an age cut-off of 40 years.

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Article Synopsis
  • Triple-negative breast cancer (TNBC) is complex, displaying various biological characteristics, and a study called Japan Breast Cancer Research Group 22 is exploring how TNBC responds to different chemotherapy treatments based on its homologous recombination deficiency (HRD) status.
  • The study involved patients under 65 with either high HRD or specific gene mutations, who received randomized chemotherapy regimens, with treatment effectiveness measured by the absence of residual cancer cells post-therapy.
  • Results from 66 samples showed that smaller tumors had more CD8 T cells, while higher densities of CD4 T cells were linked to complete pathological responses, suggesting that these immune cells could predict treatment outcomes regardless of other genetic factors.
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While clinical trials have evolved and improved over time, fundamental changes are needed to reflect the outcomes of great relevance to the institutions where they are performed, by integrating scientific rationale and society's movement to increase efficiency, accountability, and transparency by fast integrating the next-generation advances offered by omics technology and artificial intelligence. Several global clinical and exploratory collaborative studies that achieved successful outcomes in terms of patients' survival, drug toxicity, efficacy, safety, biomarkers, and consensus reached to improve good clinical practices are addressed in this article. Going forward, through collaborations, cooperation, and intellectual curiosity many more advances can be made in clinical trial approaches that can bring transparency, accountability, best outcomes, and develop friendship with trust among all the involved.

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