Richa Dawar

Bio: Richa Dawar is an academic researcher from University of Miami. The author has contributed to research in topics: Internal medicine & Oncology. The author has an hindex of 3, co-authored 12 publications receiving 45 citations. Previous affiliations of Richa Dawar include Roswell Park Cancer Institute.

Therapeutic strategies in RET gene rearranged non-small cell lung cancer

Abstract: The recent approvals by the Food and Drug Administration several tumor-agnostic drugs have resulted in a paradigm shift in cancer treatment from an organ/histology-specific strategy to biomarker-guided approaches. RET gene fusions are oncogenic drivers in multiple tumor types and are known to occur in 1–2% of non-squamous NSCLC patients. RET gene fusions give rise to chimeric, cytosolic proteins with constitutively active RET kinase domain. Standard therapeutic regimens provide limited benefit for NSCLC patients with RET fusion-positive tumors, and the outcomes with immunotherapy in the these patients are generally poor. Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are potent and selective inhibitors that target RET alterations, including fusions and mutations, irrespective of the tissue of origin. Recently, the results from the LIBRETTO-001 and ARROW clinical trials demonstrated significant clinical benefits with selpercatinib and pralsetinib respectively, in NSCLC patients with RET gene fusions, with tolerable toxicity profiles. These studies also demonstrated that these RET-TKIs crossed the blood brain barrier with significant activity. As has been observed with other TKIs, the emergence of acquired resistance may limit long-term efficacy of these agents. Therefore, understanding the mechanisms of resistance is necessary for the development of strategies to overcome them.

Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer

Abstract: METex14 skipping mutations occur in about 3-4% of lung adenocarcinoma patients and 1-2% of patients with other lung cancer histology. The MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are established oncogenic drivers of NSCLC. A mutation that results in loss of exon 14 in the MET gene leads to dysregulation and inappropriate signaling that is associated with increased responsiveness to MET TKIs. Results from GEOMETRY mono-1 and VISION Phase I/II clinical trials demonstrated significant clinical activity in patients treated with the MET Exon 14 skipping mutation inhibitors capmatinib and tepotinib with tolerable toxicity profile. In the GEOMETRY mono-1 trial, capmatinib was especially active in treatment-naive patients supporting the upfront testing of this oncogenic driver. Tepotinib demonstrated superior activity in the pretreated patients in the VISION trial. Savolitinib is another MET TKI that has shown efficacy in the first- and second-line settings, including patients with aggressive pulmonary sarcomatoid carcinoma. These studies have demonstrated that these TKIs can cross the blood brain barrier and demonstrated some activity toward CNS metastases. MET Exon 14 skipping mutation is detected by NGS-based testing of liquid or tissue biopsies, with preference for RNA-based NGS. The activity of capmatinib and tepotinib is limited by the development of acquired resistance. Current research is focused on strategies to overcome resistance and improve the effectiveness of these agents. Our aim is to review the current status of MET Exon 14 skipping mutation as it pertains NSCLC.

Tibialis Anterior Muscle Hernia: A Rare Cause of Leg Pain

Abstract: Muscle herniation of lower limb is a rare clinical entity. Tibialis anterior muscle hernia most commonly occurs as a result of an acquired fascial defect, often secondary to trauma. Most of them are asymptomatic and do not pose a diagnostic or therapeutic challenge. Large symptomatic hernias of leg are unusual and their treatment is controversial. W e report such a case of large tibialis anterior muscle hernia that presented with chronic leg pain and was treated successfully by longitudinal fasciotomy. Tibialis anterior, Hernia, Leg pain, Fasciotomy

Circulating glioma biomarkers

Abstract: Validated biomarkers for patients suffering from gliomas are urgently needed for standardizing measurements of the effects of treatment in daily clinical practice and trials. Circulating body fluids offer easily accessible sources for such markers. This review highlights various categories of tumor-associated circulating biomarkers identified in blood and cerebrospinal fluid of glioma patients, including circulating tumor cells, exosomes, nucleic acids, proteins, and oncometabolites. The validation and potential clinical utility of these biomarkers is briefly discussed. Although many candidate circulating protein biomarkers were reported, none of these have reached the required validation to be introduced for clinical practice. Recent developments in tracing circulating tumor cells and their derivatives as exosomes and circulating nuclear acids may become more successful in providing useful biomarkers. It is to be expected that current technical developments will contribute to the finding and validation of circulating biomarkers.

Muscle hernias of the leg: A case report and comprehensive review of the literature:

Abstract: A case involving a retired, elderly male war veteran with a symptomatic peroneus brevis muscle hernia causing superficial peroneal nerve compression with chosen surgical management is presented. Symptomatic muscle hernias of the extremities occur most commonly in the leg and are a rare cause of chronic leg pain. Historically, treating military surgeons pioneered the early documentation of leg hernias observed in active military recruits. A focal fascial defect can cause a muscle to herniate, forming a variable palpable subcutaneous mass, and causing pain and potentially neuropathic symptoms with nerve involvement. While the true incidence is not known, the etiology has been classified as secondary to a congenital (or constitutional) fascial weakness, or acquired fascial defect, usually secondary to direct or indirect trauma. The highest occurrence is believed to be in young, physically active males. Involvement of the tibialis anterior is most common, although other muscles have been reported. Dynamic ultrasonography or magnetic resonance imaging is often used to confirm diagnosis and guide treatment. Most symptomatic cases respond successfully to conservative treatment, with surgery reserved for refractory cases. A variety of surgical techniques have been described, ranging from fasciotomy to anatomical repair of the fascial defect, with no consensus on optimal treatment. Clinicians must remember to consider muscle hernias in their repertoire of differential diagnoses for chronic leg pain or neuropathy. A comprehensive review of muscle hernias of the leg is presented to highlight their history, occurrence, presentation, diagnosis and treatment.

Mechanism of immunomodulatory drugs' action in the treatment of multiple myeloma

Abstract: Although immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, are widely used in the treatment of multiple myeloma (MM), the molecular mechanism of IMiDs' action is largely unknown. In this review, we will summarize recent advances in the application of IMiDs in MM cancer treatment as well as their effects on immunomodulatory activities, anti-angiogenic activities, intervention of cell surface adhesion molecules between myeloma cells and bone marrow stromal cells, anti-inflammatory activities, anti-proliferation, pro-apoptotic effects, cell cycle arrest, and inhibition of cell migration and metastasis. In addition, the potential IMiDs' target protein, IMiDs' target protein's functional role, and the potential molecular mechanisms of IMiDs resistance will be discussed. We wish, by presentation of our naive discussion, that this review article will facilitate further investigation in these fields.

NK Cells in the Treatment of Hematological Malignancies.

Abstract: Natural killer (NK) cells have the innate ability to kill cancer cells, however, tumor cells may acquire the capability of evading the immune response, thereby leading to malignancies. Restoring or potentiation of this natural antitumor activity of NK cells has become a relevant therapeutic approach in cancer and, particularly, in hematological cancers. The use of tumor-specific antibodies that promote antibody-dependent cell-mediated cytotoxicity (ADCC) through the ligation of CD16 receptor on NK cells has become standard for many hematologic malignancies. Hematopoietic stem cell transplantation is another key therapeutic strategy that harnesses the alloreactivity of NK cells against cancer cells. This strategy may be refined by adoptive transfer of NK cells that may be previously expanded, activated, or redirected (chimeric antigen receptor (CAR)-NK cells) against cancer cells. The antitumor activity of NK cells can also be boosted by cytokines or immunostimulatory drugs such as lenalidomide or pomalidomide. Finally, targeting immunosubversive mechanisms developed by hematological cancers and, in particular, using antibodies that block NK cell inhibitory receptors and checkpoint proteins are novel promising therapeutic approaches in these malignant diseases.

In pursuit of a moving target: nanotherapeutics for the treatment of non-Hodgkin B-cell lymphoma.

Abstract: Introduction: Non-Hodgkin lymphoma (NHL) is diagnosed in 70,000 Americans annually. Chemotherapy was the standard course of treatment until the addition of the monoclonal antibody (mAb) drug, rituximab, to therapy regimens in 1997. Although disease prognosis has improved dramatically since that time, nearly 20,000 patients succumb annually to the disease, with an average life expectancy beyond diagnosis of only 12 years. The advent of nanomedicine may fulfill the remaining need for novel therapy capable of eradicating solid tumor and disseminated B-cell lymphomas.Areas covered: This review details the current landscape of B-cell NHL and nanoparticles now being developed for its treatment. Specifically, we discuss lipid, polymer and metal nanoparticles that deliver an array of drugs, including toxins, chemotherapeutic agents and nucleic acids.Expert opinion: Because B-cell malignancies have responded quite well to new components in multi-drug regimens, nanomedicines that are mechanistically distinct from e...