Part 2 .
30. Ovarian Cancer. (19,600 equals 1.9 billion) Standard of care; Surgery: The initial treatment typically includes a hysterectomy with bilateral salpingo-oophorectomy, removing the uterus, ovaries, and fallopian tubes. Adjuvant Chemotherapy: For high-grade tumors, chemotherapy with a combination of carboplatin and paclitaxel is usually administered post-surgery.
Monepantel is being investigated for its potential in ovarian cancer treatment due to its ability to enhance the efficacy of standard chemotherapeutics like gemcitabine and doxorubicin. Preclinical studies have shown that monepantel significantly inhibits the mTOR/p70S6K signaling pathway, leading to reduced tumor growth and increased cell death in ovarian cancer cell lines. Key Findings Combination Therapy: Monepantel, when combined with pegylated liposomal doxorubicin or gemcitabine, demonstrated synergistic effects,resulting in higher rates of tumor regression in both in vitro and in vivo models. Mechanism of Action: It induces autophagy and cell cycle arrest, enhancing the anti-tumor effects of existing chemotherapy agents while reducing resistance. Conclusion These findings suggest that monepantel could serve as a valuable addition to ovarian cancer treatment regimens, warranting further clinical investigation to establish its efficacy and safety in combination therapies.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220142/
31. Pancreatic Cancer. (66,000 equals 6.6 billion) Standard of care; Surgery: Whipple procedure (pancreaticoduodenectomy) or distal pancreatectomy is performed to remove the tumor. Adjuvant Chemotherapy: Post-surgery, chemotherapy regimens like FOLFIRINOX or gemcitabine plus capecitabine are recommended to improve survival rates.
Monepantel is being explored for its potential in pancreatic cancer treatment due to its ability to inhibit the mTOR pathway, which is often dysregulated in cancer. Preclinical studies indicate that monepantel demonstrates anti-tumor activity against pancreatic cancer cell lines and xenografts, enhancing the effects of standard chemotherapeutics like gemcitabine and cisplatin. It has shown synergy when combined with these agents, leading to improved tumor regression and survival rates in animal models. Mechanism of Action: Monepantel's anticancer effects are linked to the downregulation of oncogenic signaling pathways, particularly through the inhibition of p70S6K, which is part of the mTOR signaling cascade. Conclusion While monepantel shows promise as a potential treatment for pancreatic cancer, further clinical trials are needed to validate its efficacy and safety in human subjects.
https://aacrjournals.org/cancerres/article/75/15_Supplement/LB-005/605350/Abstract-LB-005-Monepantel-a-new-first-in-class https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315739/
32. Cancer of the Stomach.(26,000 equals 2.6 billion) Standard of care; Surgery: The primary treatment is surgical resection, which may involve subtotal or total gastrectomy, depending on tumor location. Locally Advanced Disease (Stage II-III) Neoadjuvant Therapy: Chemotherapy or chemoradiation may be administered before surgery to shrink the tumor.
Monepantel has been shown to inhibit the mTOR pathway, which plays a critical role in cancer cell growth and proliferation. This inhibition can lead to reduced tumor viability and proliferation in various cancer cell lines, including gastric cancer. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315739/ 33. Cervical Cancer. (14,000 equals 1.4 billion) Standard of care; Surgery: Options include radical hysterectomy or fertility-sparing surgery (cone biopsy) for early invasive cancers. Adjuvant Therapy: Chemotherapy or radiation may be recommended based on pathology results. Currently there are no specific ongoing studies focused on monepantel's effectiveness in cervical cancer. Most research has concentrated on its anticancer properties in ovarian cancer and other tumor types. 34. Thyroid Cancer. (44,000 equals 4.4 billion) Standard of care; Surgery: Total thyroidectomy is the primary treatment for most cases, especially for larger tumors or those with aggressive features. Lobectomy may be sufficient for smaller, localized tumors. Radioactive Iodine Therapy: Administered post-surgery to eliminate any remaining thyroid tissue and treat metastases, particularly in papillary and follicular cancers. Thyroid Hormone Therapy: Lifelong hormone replacement therapy is necessary after thyroidectomy to maintain normal metabolism and suppress TSH levels, which can stimulate cancer growth.
mTOR inhibitors are being explored as potential treatments for thyroid cancer, particularly papillary thyroid carcinoma (PTC) and medullary thyroid cancer (MTC). The mTOR pathway is overactivated in thyroid cancer, contributing to tumor growth and therapy resistance. Inhibitors like everolimus and INK128 have shown effectiveness in reducing tumor growth and inducing apoptosis in thyroid cancer cells. Combining mTOR inhibitors with other targeted therapies, such as RET inhibitors, may enhance treatment efficacy in thyroid cancers with specific mutations.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263694/
35. Prostate Cancer. (300,000 equals 30 billion) Standard of care; Localized Disease: Options are active surveillance, watchful waiting, radical prostatectomy, and radiation therapy (external beam or brachytherapy). Advanced Disease: Androgen deprivation therapy (ADT) is the primary treatment, often combined with chemotherapy or novel hormonal agents. Metastatic Disease: Systemic therapies, including ADT, chemotherapy, and palliative care, are employed to manage symptoms and improve quality of life .
Monepantel is being explored for its anticancer properties, including potential applications in prostate cancer treatment. It acts as an mTOR inhibitor, which is significant in cancer cell proliferation. Clinical studies have shown that monepantel is well-tolerated and can lead to stable disease in patients with various cancers, including prostate cancer. Its efficacy may be enhanced when used in combination with other therapies, making it a candidate for further research in prostate cancer management.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220142/
36. Squamous cell carcinoma. (1,000,000 equals 50 billion) Standard of care; Surgical Excision: The most common treatment, especially for localized tumors, often with a margin of healthy tissue to ensure complete removal. Mohs Micrographic Surgery: Recommended for high-risk lesions, particularly on the face, to minimize damage to surrounding tissue while ensuring complete tumor removal. Radiation Therapy: Used for patients who are poor surgical candidates or for tumors that cannot be completely excised. Topical Therapies: Such as 5-fluorouracil or imiquimod for superficial lesions. Immunotherapy: For advanced or metastatic SCC, options include checkpoint inhibitors. mTOR inhibitors are being researched for their potential in treating squamous cell carcinoma (SCC). The PI3K/AKT/mTOR signaling pathway is often dysregulated in SCC, contributing to tumor growth and survival.
Clinical studies have shown that mTOR inhibitors, such as everolimus, can enhance the efficacy of chemotherapy in head and neck squamous cell carcinoma (HNSCC), achieving significant tumor response rates. Additionally, mTORC2 activity has been linked to tumorigenesis in esophageal squamous cell carcinoma, suggesting that targeting this pathway may improve therapeutic outcomes. Overall, mTOR inhibitors represent a promising area of investigation for SCC treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496893/
37. Hematopoietic tumours of lymphoid lineage. (I am guessing here so no figure) Standard of care; Chemotherapy: Often the first-line treatment, especially for aggressive forms like acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Radiation Therapy: Used in conjunction with chemotherapy or as a standalone treatment for localized disease. Targeted Therapies: Such as monoclonal antibodies (e.g., rituximab for B-cell lymphomas) and small molecule inhibitors. Stem Cell Transplant: Considered for eligible patients, particularly in cases of relapsed or refractory disease. Immunotherapy.
mTOR inhibitors, such as everolimus and temsirolimus, are being investigated for their efficacy in treating hematopoietic tumors of lymphoid lineage, particularly B-cell malignancies like diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). These inhibitors target the PI3K/Akt/mTOR signaling pathway, which is often dysregulated in these cancers, promoting cell proliferation and survival. Clinical trials have shown promising results, indicating that mTOR inhibitors can be effective either as monotherapy or in combination with other treatments, enhancing therapeutic outcomes in patients with lymphoid malignancies.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531792/
38. Leukaemia. 39. Acute lympathic Leukaemia. (see below) 40. Acute lymphoblastic Leukaemia. (Combined with 38/39 approximately 59,000 equals 5.9 billion) I have included 38/39/40 in the one answer. Standard of care; Acute Myeloid Leukemia (AML): Treatment typically involves combination chemotherapy for remission induction, followed by consolidation therapy. Targeted therapies and stem cell transplants may be used for certain subtypes. Acute Lymphoblastic Leukemia (ALL): Standard treatment includes induction chemotherapy, followed by consolidation and maintenance phases. Targeted therapies like tyrosine kinase inhibitors are also utilized. Chronic Myeloid Leukemia (CML): First-line treatment often involves tyrosine kinase inhibitors.
Monepantel is being studied for its potential in treating leukemia, particularly in the context of the human T-cell leukemia virus type 1 (HTLV-1). Preliminary results indicate that monepantel can kill HTLV-1-transformed leukemia cell lines and inhibit viral protein production, suggesting both anticancer and antiviral effects. This dual action may offer new therapeutic avenues for patients affected by HTLV-1-related leukemia, which currently lacks effective treatments.
https://unauthorised investment advice/health/preliminary-results-show-pharmausts-monepantel-drug-is-effective-against-leukaemia-virus-htlv-1/
41. B cell Lymphoma. (80,000 equals 8 billion) Monepantel was relatively successful on dogs treated for Lymphoma B. To be more successful owners need to do white blood cell tests every month at home ( eBay ) if increase in WBC see your veterinarian and ask about Lymphoma B. The disease is insidious and fast so if we can nip it in the blood the veterinarian based drugs will help. If left too long before diagnosis the prognosis is poor. Monepantel can still be administered to dogs but costs may prohibit.
https://sashvets.com/diseases/lymphoma-cancer-dogs/
https://www.dogcancer.com/podcast/trials-and-research/monepantel-a-future-treatment-for-dog-lymphoma-dr-kim-agnew/
So let's have a look at humans. The standard of care for B-cell lymphoma in humans primarily involves chemotherapy, often using regimens like R-CHOP, which combines rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone. For localized disease, radiation therapy may also be included. Advanced cases may require high-dose chemotherapy or stem cell transplantation. Clinical trials are encouraged for access to new therapies, including targeted treatments and immunotherapies like CAR-T cell therapy.
42. T cell Lymphoma. (10,000 equals 1 billion) Monepantel is currently being investigated as a treatment for canine lymphoma, particularly B-cell lymphoma, rather than T-cell lymphoma in humans. Originally developed as a sheep dewormer, it has shown promise in clinical trials for dogs, demonstrating safety and a potential to stabilize the disease without the severe side effects typical of chemotherapy. The drug is administered orally, allowing for at-home treatment, which may enhance the quality of life for pets undergoing therapy. However, its efficacy in human T-cell lymphoma remains unestablished. It shall remain that way. T cell pathway is resistant to Monepantel mechanism of action from my perspective.
43. Hodgkin lymphoma. (8,000 equals 800 million) Standard of care; Early-stage favorable disease: Often treated with 2-4 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by involved-field radiation. Early-stage unfavorable disease: Usually requires more intensive chemotherapy, potentially followed by radiation. Advanced-stage disease: Treated primarily with chemotherapy, with radiation reserved for specific cases.
mTOR inhibitors, such as rapamycin and everolimus, are being explored as potential treatments for Hodgkin lymphoma due to the high activity of the mTOR pathway observed in this disease. Studies indicate that over 90% of Hodgkin lymphoma cases exhibit elevated mTOR activity, which is linked to cell proliferation and survival. In preclinical models, rapamycin has demonstrated the ability to inhibit tumor growth and induce apoptosis in Hodgkin lymphoma cells, suggesting that mTOR inhibition could enhance the effectiveness of standard therapies and reduce toxicity. Clinical trials are ongoing to evaluate the efficacy of mTOR inhibitors, both alone and in combination with other agents, for relapsed or refractory cases of Hodgkin lymphoma.
https://haematologica.org/article/view/haematol.2021.278853
44. Non Hodgkin lymphoma.(80,000 equals 8 billion) Standard of care; Indolent (low-grade) NHL: Often monitored with "watchful waiting" if asymptomatic. Treatment may include radiation for localized cases or chemotherapy for widespread disease. Aggressive (high-grade) NHL: Typically treated with combination chemotherapy regimens, often including rituximab. Advanced cases: May require stem cell transplantation or targeted therapies. mTOR inhibitors, such as temsirolimus and everolimus, are being investigated for their potential in treating non-Hodgkin lymphoma (NHL). The PI3K/Akt/mTOR signaling pathway is often activated in various NHL subtypes, including diffuse large B-cell lymphoma and mantle cell lymphoma, contributing to cell proliferation and survival.
Clinical trials have shown that mTOR inhibitors can be effective as monotherapy or in combination with other treatments, particularly in relapsed or refractory cases. Temsirolimus has received FDA approval for mantle cell lymphoma, while everolimus is still under evaluation for NHL.
https://pubmed.ncbi.nlm.nih.gov/23693095/
45. Hairy cell lymphoma. (8,000 equals 800 million) Standard of care ; Cladribine: A purine nucleoside analog, often the first-line treatment, leading to high response rates. Pentostatin: Another chemotherapy option, effective in treating hairy cell leukemia. Rituximab: Often used in combination with other therapies, particularly for relapsed cases. BRAF inhibitors (e.g., vemurafenib): Target the BRAF V600E mutation commonly found in hairy cell leukemia. Interferon-alpha: Used in some cases, though less common now. Splenectomy: Considered for symptomatic splenomegaly or if other treatments are ineffective. Clinical studies have shown that mTOR inhibitors can induce apoptosis and inhibit growth in HCL cells. They may be used as monotherapy or in combination with other treatments, especially for relapsed or refractory cases. Ongoing research aims to better understand their efficacy and optimal use in HCL therapy, potentially improving outcomes for patients with this.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531792/
46. Mantle cell lymphoma.(1,500 equals 150 million) Standard of care; preferred treatment is high-dose chemotherapy with a cytarabine-based regimen, followed by autologous stem cell transplantation. This approach often includes induction with rituximab and consolidation therapy. Transplant-ineligible patients: Common regimens include bendamustine combined with rituximab, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), or VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone). Relapsed/refractory cases: Targeted therapies like ibrutinib or acalabrutinib.
Research indicates that monepantel inhibits the mTOR pathway, which is relevant in various cancers, but specific studies on its efficacy in MCL are lacking. Further investigation is needed to determine its potential role in treating MCL.
47. Myeloma. (35,000 equals 3.5 billion) Standard of care; Induction Therapy: This is the initial treatment aimed at reducing the number of myeloma cells. Common regimens include combinations such as bortezomib, lenalidomide, and dexamethasone (VRd) or daratumumab with lenalidomide and dexamethasone (Dara-Rd). Autologous Stem Cell Transplant (ASCT): For eligible patients, this follows induction therapy to achieve deeper remission. Maintenance Therapy: Post-transplant, patients often receive maintenance therapy, typically with lenalidomide, to prolong remission. mTOR inhibitors, such as temsirolimus and everolimus, are being investigated for their potential in treating multiple myeloma (MM).
The mTOR pathway is crucial for cell growth and survival, and its dysregulation is common in MM. Efficacy: Studies show that mTOR inhibitors can induce apoptosis and enhance the effectiveness of other therapies, such as proteasome inhibitors and venetoclax, by modulating apoptotic pathways.
https://pubmed.ncbi.nlm.nih.gov/24001224/
48. Burketts Lymphoma.(1,200 equals 120 million) Standard of care; Burkitt lymphoma treatment primarily involves intensive chemotherapy, often requiring hospitalization. Common regimens include CODOX-M/IVAC and DA-EPOCH-R, which are tailored based on age and risk level. Rituximab is frequently added to enhance effectiveness. For high-risk patients, aggressive treatment is essential, while low-risk cases may require less intensive approaches. Intrathecal therapy is also utilized to prevent central nervous system involvement. Newer studies suggest less toxic alternatives may be effective, particularly for adults.
mTOR inhibitors are being investigated as potential treatments for Burkitt lymphoma due to their ability to target the PI3K/Akt/mTOR signaling pathway, which is often activated in this aggressive cancer. NVP-BEZ235: This dual PI3K/mTOR inhibitor has shown significant inhibition of Burkitt lymphoma cell proliferation and induced apoptosis in cell lines like CA46 and Raji, primarily through G1/G0 phase arrest and reduced phosphorylation of key signaling proteins. Rapamycin: Studies indicate that rapamycin effectively inhibits proliferation and induces apoptosis in Burkitt lymphoma cells, suggesting its potential as a therapeutic agent. Omipalisib (GSK458): This pan-PI3K/mTOR inhibitor demonstrated dose-dependent anti-tumor activity and enhanced the effects of conventional chemotherapy in vitro, indicating its promise for improving treatment outcomes. Overall, these findings support further research into mTOR inhibitors as part of Burkitt lymphoma therapy.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955151/
49. Myelongenous Lymphoma. (20,000 equals 2 billion) Standard of care; Initial treatment often includes combination chemotherapy, potentially with targeted therapies like midostaurin for specific genetic mutations. In some cases, a stem cell transplant may be considered, especially for achieving remission or treating recurrent disease.
mTOR inhibitors, such as rapamycin and its derivatives (rapalogs), are being explored for their potential in treating hematological malignancies, including acute myelogenous leukemia (AML). These inhibitors target the mTOR signaling pathway, which is often dysregulated in AML, contributing to chemotherapy resistance. Studies have shown that mTOR inhibitors can enhance the sensitivity of AML cells to chemotherapy and impair leukemic stem cell function. However, their efficacy as single agents is limited, and combination therapies are being investigated to improve outcomes.
50. Myelodyspastic syndrome. (58,000 equals 5.8 billion) Standard of care; standard of care for myelodysplastic syndromes (MDS) includes supportive care, drug therapy, and potentially stem cell transplantation, depending on the patient's risk category and overall health. Supportive care often involves blood transfusions and treatment of infections. Drug therapies may include hypomethylating agents like azacitidine and decitabine, particularly for higher-risk MDS, and lenalidomide for patients with specific genetic abnormalities such as del(5q). Stem cell transplantation is considered for younger, healthier patients, as it offers the potential for a cure.
mTOR inhibitors, such as rapamycin and its analogs (Rapalogs), are being investigated for their potential in treating myelodysplastic syndromes (MDS). The mTOR pathway is often activated in high-risk MDS, and studies have shown that mTOR inhibitors can induce apoptosis in MDS cells. However, their efficacy varies, with some studies indicating limited benefits, particularly in low-risk MDS patients. For example, sirolimus showed some activity in advanced MDS but was not effective in low-risk cases. More research is needed to fully understand their therapeutic potential in MDS.
51. Promyelocyte Leukaemia. (1,000 equals 10 million) The standard of care for acute promyelocytic leukemia (APL) involves the use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) for induction and consolidation therapy, particularly in patients with low- to intermediate-risk disease (white blood cell count ≤ 10,000/μL). This combination has significantly improved survival rates and allows many patients to avoid traditional chemotherapy. For high-risk patients, additional cytoreductive chemotherapy may be used alongside ATRA and ATO. Rapid initiation of treatment and management of complications like differentiation syndrome are crucial for optimal outcomes.
mTOR inhibitors, such as rapamycin and its analogs, are being explored for their potential in treating acute promyelocytic leukemia (APL) by targeting the PI3K/Akt/mTOR signaling pathway. This pathway is crucial for cell growth and survival and is often dysregulated in hematological malignancies. Although mTOR inhibitors have shown promise in other types of leukemia, their specific application in APL is less documented. Research indicates that mTOR inhibitors can enhance chemotherapy responses and induce apoptosis in leukemia cells, but further studies are needed to establish their efficacy in APL.
https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.611690/full
52. Mesenchymal tumours.(Rare unable to guesstimate) Standard of care; Surgery: This is the primary treatment for most mesenchymal tumors, aiming to remove the tumor entirely. Radiation Therapy: Often used pre- or post-operatively to reduce recurrence risk, especially in high-grade tumors. Chemotherapy: Its role varies depending on the tumor type and grade, and is more common in aggressive or metastatic cases. mTOR inhibitors are being explored for their potential in treating mesenchymal tumors by targeting the mTOR signaling pathway, which is involved in cell growth and survival. This pathway is often dysregulated in various cancers, including mesenchymal tumors. mTOR inhibitors, such as rapamycin and its analogs (Rapalogs), can induce tumor cell apoptosis and cell cycle arrest. While they have shown promise in preclinical studies, their clinical efficacy in mesenchymal tumors specifically is still under investigation, and more research is needed to establish their role in standard treatment protocols.
53. Fibrosarcoma . (1,500 equal 150 million) The standard of care for fibrosarcoma involves a multidisciplinary approach primarily focused on surgical resection. Surgery is the mainstay treatment, aiming for complete removal of the tumor with clear margins to minimize recurrence risk. Radiation therapy may be used pre- or post-operatively, particularly for tumors at higher risk of recurrence or those that are not easily resectable. Chemotherapy is less commonly used but may be considered in high-grade or metastatic cases. Regular follow-up is essential to monitor for local recurrence and metastasis.
mTOR inhibitors are being investigated for their potential in treating fibrosarcoma by targeting the dysregulated mTOR signaling pathway, which is implicated in cancer cell growth and survival. While mTOR inhibitors like rapamycin and its derivatives (e.g., temsirolimus, everolimus) have shown efficacy in various cancers, their specific application in fibrosarcoma is still under study. These inhibitors can induce tumor cell cycle arrest and apoptosis, but clinical results in fibrosarcoma are not yet well-documented, necessitating further research to establish their effectiveness and optimal use in this context.
54. Rhadomyosarcoma. (350 equals 35 million) Standard of care; Chemotherapy: Standard regimens include vincristine, actinomycin, and cyclophosphamide/ifosfamide, with the addition of maintenance chemotherapy in high-risk cases. Surgery: Aims to remove the tumor completely when feasible. Radiation Therapy: Used for local control, especially when complete surgical resection is not possible. mTOR inhibitors are being investigated for their potential in treating rhabdomyosarcoma, a type of mesenchymal tumor.
The mTOR signaling pathway is often activated in rhabdomyosarcoma, but mTOR complex 1 inhibition has shown limited success so far. While mTOR inhibitors like rapamycin and its derivatives have been evaluated in clinical trials for various cancers, including sarcomas, their effectiveness specifically in rhabdomyosarcoma requires further research.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409076/
55. Astrocytoma. (1500 equals 150 million) Standard of care; Grade I Astrocytoma: Surgery is the primary treatment, aiming for total removal of the tumor when accessible. Radiation therapy may follow if needed. Grade II Astrocytoma: Treatment involves surgery, possibly followed by radiation therapy. Complete surgical removal is often challenging due to tumor infiltration into surrounding tissues. Grade III Astrocytoma: Standard treatment includes surgery, radiation therapy, and chemotherapy with agents like temozolomide. Grade IV Astrocytoma (Glioblastoma): Treatment typically involves surgery, followed by radiation and chemotherapy with temozolomide.
mTOR inhibitors, such as everolimus and sirolimus, are used in the treatment of subependymal giant cell astrocytomas (SEGAs), particularly in patients with tuberous sclerosis complex (TSC). These inhibitors target the mTOR signaling pathway, which is often dysregulated in these tumors. Everolimus has been shown to induce regression of astrocytomas in TSC and is approved for this use. While mTOR inhibitors are effective in managing SEGAs, their use in other types of astrocytomas is still under investigation.
https://pubmed.ncbi.nlm.nih.gov/27739368/
56. Neuroblastoma. (640 equals 64 million) Standard of care ; Low-Risk Neuroblastoma: Treatment may include surgery followed by observation, or observation alone in certain infants. Chemotherapy is used if the tumor cannot be surgically removed or continues to grow. Intermediate-Risk Neuroblastoma: Treatment often involves chemotherapy to shrink the tumor, followed by surgery. Radiation therapy may be used if the tumor persists after chemotherapy. High-Risk Neuroblastoma: This involves a multi-modal approach with induction chemotherapy, surgical resection, consolidation with autologous stem cell transplantation (ASCT) and radiotherapy. mTOR inhibitors are being explored for their potential in treating neuroblastoma, particularly in cases with MYCN amplification, which often respond poorly to standard therapies. The mTOR signaling pathway is frequently deregulated in neuroblastoma, promoting tumor growth and survival. Studies have shown that mTOR inhibitors, like temsirolimus, can synergistically enhance the efficacy of other treatments, such as BET protein inhibitors, by inducing cell cycle arrest and apoptosis in neuroblastoma cells.
Additionally, newer mTOR inhibitors like Torin-2 have demonstrated superior efficacy in reducing neuroblastoma cell viability compared to older inhibitors like rapamycin.
https://www.medsci.org/v18p0137.htm
57. Glioma. (19,000 equals 1.8 billion) Standard of care; Surgery: Maximal safe resection is the first step to remove as much of the tumor as possible while preserving neurological function. Radiation Therapy: This is usually administered post-surgery to target remaining tumor cells, often in combination with chemotherapy. Chemotherapy: Temozolomide is the standard chemotherapy used alongside radiation therapy and as adjuvant treatment. Tumor Treating Fields (TTFields): This FDA-approved therapy uses alternating electric fields to disrupt cancer cell division.
mTOR inhibitors are being investigated for their potential in treating gliomas, including glioblastomas, due to the dysregulation of the mTOR pathway in these tumors. Traditional mTORC1 inhibitors like rapamycin have shown limited success, partly due to feedback loops that activate other pathways.
58. Schwannomas. (4,000 equals 400 million) Standard of care; For small, asymptomatic schwannomas, especially vestibular schwannomas, regular monitoring with MRI is often recommended to track tumor growth. Surgical Resection: This is the primary treatment for symptomatic or growing schwannomas. The goal is to remove the tumor while preserving nerve function as much as possible. Radiation Therapy: Stereotactic radiosurgery, such as Gamma Knife or CyberKnife, is used for patients who are not surgical candidates or to treat residual or recurrent tumors. It is also an option for small tumors where hearing preservation is a priority.
mTOR inhibitors are being explored as a potential treatment for schwannomas, particularly those associated with neurofibromatosis type 2 (NF2). The mTOR signaling pathway is often activated in NF2-related tumors due to the loss of the NF2 tumor suppressor gene, leading to increased tumor growth. Studies have shown that mTORC1 inhibitors, such as rapamycin, can reduce the severity of NF2-related schwannomas in both in vitro and in vivo models. Additionally, dual mTORC1/2 inhibitors like AZD2014 have demonstrated effectiveness in combination with other drugs, such as dasatinib, in reducing tumor growth. These findings suggest that mTOR inhibitors could be a promising therapeutic strategy for managing schwannomas, though further clinical trials are needed to confirm their efficacy.
https://academic.oup.com/neuro-oncology/article/17/2/189/2325144
59. Seminoma. (8,000 equals 800 million) Standard of care; Stage I Seminoma: The primary treatment is radical inguinal orchiectomy, which is often curative. Post-surgery options include: Surveillance: Preferred for many patients, involving regular monitoring without immediate further treatment. Adjuvant Therapy: Options include single-agent carboplatin (1-2 cycles) or radiotherapy (20 Gy) to reduce relapse risk. Stage IIA/B Seminoma: Treatment typically involves: Radiotherapy or Chemotherapy (BEP: bleomycin, etoposide, cisplatin). Advanced Stages (IIC, III): Chemotherapy is the mainstay.
mTOR inhibitors are being studied for their potential role in treating seminomas, particularly due to the involvement of the mTOR signaling pathway in tumor growth. Research has shown that rapamycin, an mTOR inhibitor, can induce apoptosis in seminoma cells, specifically in the TCam-2 cell line, by inhibiting the G1-S transition of the cell cycle and reducing mTOR activity. This suggests that targeting the mTOR pathway could be a viable therapeutic strategy for seminomas, warranting further investigation into the efficacy of mTOR inhibitors in clinical settings for this type of cancer.
https://pubmed.ncbi.nlm.nih.gov/36598515/
60. Teratocarcinoma. (Unable to guesstimate) Standard of care; Surgery: Radical surgical resection is the primary treatment, especially for localized tumors. Complete excision is crucial to minimize the risk of recurrence. Chemotherapy: For patients with non-seminomatous germ cell tumors, including teratocarcinoma, adjuvant chemotherapy is often indicated, particularly if there are malignant elements. Common regimens include BEP (bleomycin, etoposide, cisplatin) or EP (etoposide, cisplatin). mTOR inhibitors are being explored for their potential role in treating teratocarcinoma, particularly due to the involvement of the mTOR signaling pathway in tumor growth and survival.
Research indicates that mTOR inhibitors, such as rapamycin and its analogs (rapalogs), can inhibit cell proliferation and induce apoptosis in various cancer types, including teratocarcinoma. Additionally, newer dual mTORC1/2 inhibitors are under investigation, which may provide enhanced efficacy against tumors resistant to traditional therapies. However, specific studies on the effectiveness of mTOR inhibitors in teratocarcinoma are limited, necessitating further research to establish their clinical utility in this context.
62. Osteosarcoma. (400 equals 4 million) Standard of care; Crucial for localized osteosarcoma, aiming for complete removal of the tumor with clear margins. In some cases, limb-salvage procedures are preferred over amputation. Chemotherapy: Typically involves a multi-agent regimen, often including doxorubicin, cisplatin, and high-dose methotrexate (MAP). Neoadjuvant chemotherapy is commonly administered before surgery to shrink the tumor, followed by adjuvant chemotherapy to prevent recurrence.
Studies have shown that combining mTOR inhibitors with other therapies, such as cyclin-dependent kinase (CDK) inhibitors, enhances anti-tumor effects in osteosarcoma models. Additionally, combinations of mTOR inhibitors with VEGF inhibitors have demonstrated improved efficacy in preclinical models, particularly in overcoming chemotherapy resistance. However, clinical efficacy remains to be fully established, necessitating further research to optimize treatment strategies involving mTOR inhibitors for osteosarcoma.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226621/
63. Xenoderoma Pigmentosum (1,300 equals 13 million) Standard of care; No cure .UV protection Surveillance: Regular dermatological examinations every three months for skin cancer surveillance, along with annual ophthalmological assessments for eye complications. Treatment of Skin Lesions: Early surgical removal of skin cancers and precancerous lesions, with options for cryotherapy, topical chemotherapy (e.g., 5-fluorouracil), and laser therapy. Neurological Management: Regular neurological evaluations, as some patients may develop progressive neurological symptoms. Chemoprevention: Use of oral isotretinoin and topical agents like imiquimod to reduce skin cancer risk.
There is currently limited research on the use of mTOR inhibitors specifically for xeroderma pigmentosum (XP). XP is primarily managed through preventive measures and treatments aimed at reducing skin cancer risk due to UV sensitivity. While mTOR inhibitors have shown promise in various cancers, their application in XP is not well-established. However, potential future therapies may explore the role of mTOR inhibition in enhancing DNA repair mechanisms or in combination with other treatments, such as gene therapy or immunotherapy, which are under investigation for XP management. Further studies are necessary to determine the efficacy and safety of mTOR inhibitors in this context.
64. Keratoctanthoma . (350,000 equals 35 billion)Standard of care; Surgical Excision: The treatment of choice is standard excision, which effectively removes the tumor and minimizes recurrence, with rates ranging from 4% to 8%. Mohs micrographic surgery is recommended for aggressive lesions or those in cosmetically sensitive areas, achieving lower recurrence rates of 2% to 8%. Alternative Treatments: In cases where surgery is not feasible, other options include electrodessication and curettage, topical chemotherapy (e.g., 5-fluorouracil, imiquimod), and intralesional therapies like methotrexate or bleomycin. These alternatives may be considered for patients with multiple lesions.
mTOR inhibitors are being explored for their potential role in treating keratoacanthomas (KAs), particularly due to the activation of the mTOR signaling pathway in these tumors. Studies have shown that mTORC1 is active in keratoacanthoma cells, indicating that targeting this pathway may be beneficial. Research suggests that mTOR inhibitors, such as rapamycin and its analogs, can reduce keratinocyte proliferation and may help manage keratoacanthomas, especially in cases where traditional surgical options are not viable. Additionally, systemic mTOR inhibition has demonstrated effectiveness in reducing skin lesions in related conditions, suggesting a potential therapeutic avenue for keratoacanthoma management.
https://journals.lww.com/md-journal/fulltext/2015/09040/keratoacanthoma_of_the_lip__activation_of_the_mtor.20.aspx
65. Thyroid Follicular Cancer. (44,000 equals 4.4 billion) Standard of care; Surgery: Total thyroidectomy is the primary treatment, aiming to remove the tumor completely. In some cases, a lobectomy may be performed if the tumor is small and localized. Radioactive Iodine (RAI) Therapy: Post-surgery, RAI is often used to ablate any remaining thyroid tissue and to treat metastatic disease, particularly if the cancer is iodine-sensitive. Thyroid Hormone Suppression Therapy: Patients typically receive levothyroxine to suppress thyroid-stimulating hormone (TSH), which can stimulate cancer growth.
Studies have shown that mTOR inhibitors like everolimus can lead to disease stabilization in patients with advanced thyroid cancers, including those with follicular cell origin. In clinical trials, everolimus demonstrated a response rate in patients with radioactive iodine-refractory thyroid cancer, with significant disease control observed in a substantial proportion of participants. Additionally, combining mTOR inhibitors with other therapies, such as BRAFV600E inhibitors, has shown enhanced anti-tumor effects, suggesting a potential strategy for more effective treatment regimens in advanced cases.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046096/
66. Kaposi’s sarcoma. (2,000 equals 20 million) Standard of care; Local Treatments: For limited skin lesions, options include radiation therapy, cryotherapy, topical retinoids, or intralesional chemotherapy. Systemic Treatments: For more extensive disease, systemic chemotherapy is often recommended. First-line agents include pegylated liposomal doxorubicin and paclitaxel. Pomalidomide has also received accelerated approval for use in KS. HIV Management: In HIV-associated KS, controlling the HIV infection with antiretroviral therapy is crucial, as it can significantly reduce KS lesions.
mTOR inhibitors, such as rapamycin (sirolimus), are being investigated as potential treatments for Kaposi's sarcoma (KS) due to their role in inhibiting tumor growth and angiogenesis. Research indicates that mTOR plays a significant role in the transformation of endothelial cells by the KS-associated herpesvirus, making it a target for therapy. Studies have shown that rapamycin can effectively reduce KS lesions, although it may transiently activate Akt, which could limit its effectiveness. Novel dual inhibitors like PI-103 have demonstrated greater efficacy in preclinical models by simultaneously targeting both the mTOR and PI3K pathways, leading to improved inhibition of cell proliferation and survival in KS cells. These findings suggest that mTOR inhibitors, particularly in combination with other therapies.
https://pubmed.ncbi.nlm.nih.gov/23382046/#:~:text=Together%2C%20the%20results%20show%20that,other%20cancers%20of%20endothelial%20origin.
67. Diseases related to transplant rejection. (10,000 equals 100 million) Standard of care; Immunosuppressive Therapy: All transplant recipients require lifelong immunosuppressive medications to prevent rejection. This typically includes a combination of drugs such as corticosteroids, calcineurin inhibitors (e.g., tacrolimus, cyclosporine), and antimetabolites (e.g., mycophenolate mofetil). Kidney Transplantation.
mTOR inhibitors are commonly used in kidney transplantation to reduce the incidence of acute rejection and improve long-term graft survival. They can be initiated soon after surgery and are often combined with calcineurin inhibitors (CNIs) to optimize immunosuppression while minimizing CNI-related nephrotoxicity. Reduction of Viral Infections: mTOR inhibitors have been associated with a lower incidence of viral infections, particularly cytomegalovirus (CMV), in kidney transplant recipients, which is crucial as these infections can complicate post-transplant recovery.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322634/
69 Chronic Inflammatory Disease. (huge numbers but won't add these) Standard of care; Pharmacological Treatments: Use of anti-inflammatory medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) for autoimmune conditions. Lifestyle Modifications: Emphasis on diet and exercise to reduce inflammation, including weight management, a balanced diet rich in anti-inflammatory foods, and regular physical activity.
Monepantel, an anthelmintic drug primarily used to treat parasitic infections, has shown potential anti-inflammatory properties that may be relevant for chronic inflammatory diseases. Research indicates that monepantel can modulate immune responses, potentially reducing inflammation in various conditions. Monepantel acts on the mTOR pathway, which is crucial in regulating inflammation and immune responses. This suggests it may help manage chronic inflammatory diseases by inhibiting excessive inflammatory signaling Research Findings: Preliminary studies have indicated that monepantel might reduce markers of inflammation, providing a basis for further exploration in chronic inflammatory conditions, although specific clinical applications are still under investigation.
https://www.researchgate.net/publication/271387573_Monepantel_exerts_anti-inflammatory_properties_in_murine_macrophages_possible_mediation_through_the_inhibition_of_NF-kB_signalling
Reference: Perplexity Ai
In the studies supplied I have included monepantel as a mtor inhibitor. Some conditions have been associated with monepantel some haven't as research is early days.
So if we add the populations involved discount by 95% then discount that again by 95% we then multiply the $100,000 per person per year.
Here is our hugely conservative number of sales per year Monepantel (off label not including MND ALS) I have not included numbers 5/11/12/13/14 as that is a general incidence of numbers but not in the life threatening category. But who knows. Include them if you wish.
So if we include 19.6 million customers/patients and we discount it twice by 95% we end up with 48,997 patients . Multiply that by PAA estimated cost of $100,000 per year and the figure comes to ball park 4.899 billion per year revenue.
So to estimate the worth of a company with $5 billion in annual sales during a potential takeover, you can use the "times revenue" valuation method. Typically, companies are valued at a revenue multiple that varies by industry.For instance, if the industry average multiple is around 2x to 5x revenue, the company's value could range from:
Low estimate (2x revenue): 5 billion×2=10 billion
High estimate (5x revenue): 5 billion×5=25 billion
Thus, the company's approximate worth could be between $10 billion and $25 billion, depending on specific industry factors and market conditions. Of course we haven't the sales, just the potential revenue. So let's discount 25 billion by 60% again for the last time.
Bargain price for ourselves to sell on is $4.50 approximately without MND. So to get that figure we have discounted the main figure by 95% then 95% again and finally 60%.
I appreciate it's ultra conservative but we haven't received a full valuation of our patents and I am just trying to fill that gap.
$4.50 per share on 500 million on issue. "Remembering I have not included MND ALS potential sales". Morgan's recent valuation of PAA was $3.20 so add that. $7.70 hard to believe, but I do now.
I have always said the "drug is too good".
Someone will say what happens of the potential acquirers don't buy after the FDA approval. Well, we sell it ourselves. Is PAA going to be able to sell it by ourselves. Yes . Plans are in action for that scenario. First week sales.
All scenarios are being looked at. We have assembled a world class team for a reason. Why wouldn't you, considering the worth and potential of Monepantel.
Some Hot Copperites have mentioned before about PAA being a dividend stock. Let's have a peek at two valuation scenarios.
PAA have stated potential revenue from MND ALS alone being 9 billion $. Of course let's discount that by 60%, leaves us with 4 billion $.
https://unauthorised investment advice/health/outstanding-milestone-fda-grants-pharmaust-orphan-drug-designation-for-monepantel/
Net profit margins of 15% at the lower scale of BP margins to be conservative. So 600 million $ profit.
Banks pay out approximately 70% of their net profits to dividends. So 70% of 600 million is 420 million divided by shares on issue. 80 cents could that be 100% franked. I will leave that to others to decide.
But since we are discounting everything in this valuation. Guess is 65% franked. If we were to combine PAA income and other income from off label purchases that equals 8 billion with a $1.60 65% franked yearly dividend.
Remember Roger Aston said in a "podcast "possibly 5 years ago. " I could sell it for 10 cents or $10". It being the sale of Pharmaust. ( It's like a mine, the more drill holes we place the better our assay knowledge is) If anyone can find that podcast of RA and post same. I would be appreciative.
It's all about time now.
Time for a song I reckon after that.
https://youtu.be/8ffc0TCGIG4?si=1P-VQ8l2UC9c7BVc
Cheers Kpax
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