Exploiting Multiple Pathways for Best-in-Class Treatment Strategies

Elusive and complex, pervasive and diverse, cancer remains one of the most challenging diseases of our lifetime. Its adaptive nature requires formidable exploration to understand tumor genesis and how treatments can be devised to suppress and kill cancer cells. We strive to be at the forefront of this research, exploiting cancer’s multiple pathways that can be inhibited or modulated, thus making the disease an excellent candidate for combination therapy.

Devising New Strategies To Treat And Defeat Cancer

We are making consistent headway against difficult-to-treat cancers with small molecule therapies that work alone and in combination with treatment regimens to precisely target different and complementary pathways.

About Genitourinary Cancers

Genitourinary cancers are those that affect the urinary tract, bladder, kidneys, ureter, prostate, testicles, penis or adrenal glands — parts of the body involved in reproduction and excretion — and include renal cell carcinoma (RCC), castration-resistant prostate cancer (CRPC) and urothelial carcinomas.1

  • The American Cancer Society’s (ACS) 2021 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.2 Clear cell RCC is the most common type of kidney cancer in adults.3 Papillary RCC accounts for about 15% of all renal cell cancers.4,5 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.2 Approximately 32,000 patients in the U.S. and over 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021, with nearly 15,000 patients in need of a first-line treatment in the U.S.6
  • According to the ACS, in 2021, approximately 250,000 new cases of prostate cancer will be diagnosed, and 34,000 people will die from the disease.2 Prostate cancer that has spread beyond the prostate and does not respond to androgen-suppression therapies — a common treatment for prostate cancer — is known as metastatic CRPC.7 Researchers estimate that in 2020, 43,000 people were diagnosed with metastatic CRPC, which has a median survival of less than two years.8,9,10
  • Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.11 Bladder cancer occurs mainly in older people, with 90% of patients aged 55 or older.12 With an estimated 84,000 new cases expected to be diagnosed in 2021, bladder cancer accounts for about 5% of all new cases of cancer in the U.S. each year.2,13 It is the fourth most common cancer in men.2

About Hepatocellular Carcinoma

More than 900,000 new cases of liver cancer are diagnosed worldwide each year, and it is a leading cause of cancer death, accounting for more than 800,000 deaths annually.14 In the U.S., the incidence of liver cancer has more than tripled since 1980. Hepatocellular carcinoma (HCC) is the most common form of liver cancer, making up about three-fourths of the estimated 42,000 new cases in the U.S. in 2021.2 HCC is the fastest-rising cause of cancer-related death in the U.S.15 Without treatment, patients with advanced HCC usually survive less than 6 months.16

About Thyroid Cancer

Approximately 44,000 new cases of thyroid cancer will be diagnosed in the U.S. in 2021. Nearly three out of four of these cases will be in women, and the disease is more commonly diagnosed at a younger age compared with most other adult cancers. Cancerous thyroid tumors include differentiated, medullary and anaplastic forms.17

  • Differentiated thyroid cancer (DTC) makes up about 90% of cases and includes papillary, follicular and Hürthle cell cancer.17 DTC is typically treated with surgery followed by ablation of the remaining thyroid with radioactive iodine, but approximately 5% to 15% of cases are resistant to radioactive iodine treatment.18,19 For these patients, life expectancy is only three to six years from the time metastatic lesions are detected.20,21,22
  • Medullary thyroid cancer (MTC) is more difficult to diagnose and treat.17 Estimates suggest that approximately 900 cases of MTC will be diagnosed in the U.S. in 2021.23

About Non-Small Cell Lung Cancer

Lung cancer is the second most common type of cancer in the U.S., with more than 235,000 new cases expected to be diagnosed in 2021.24 The disease is the leading cause of cancer-related mortality in both men and women, causing 25% of all cancer-related deaths.24 The majority (84%) of lung cancer cases are non-small cell lung cancer (NSCLC), which mainly comprise adenocarcinoma, squamous cell carcinoma and large cell carcinoma.24,25 The five-year survival rate for patients with NSCLC is 24%, but that rate falls to just 6% for those with advanced or metastatic disease.25 More than half of lung cancer cases are diagnosed at an advanced stage, and more options are needed for these patients.26

  1. National Cancer Institute Dictionary of Cancer Terms. Genitourinary System. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/genitourinary-system. Accessed March 2021.
  2. American Cancer Society: Cancer Facts & Figures 2021. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2021.pdf. Accessed March 2021.
  3. Jonasch, E., Gao, J., Rathmell, W., Renal cell carcinoma. BMJ. 2014; 349:g4797.
  4. Zhang T, Gong J, Maia MC, Pal SK. Systemic Therapy for Non-Clear Cell Renal Cell Carcinoma. Am Soc Clin Oncol Educ Book 2017;37:337–42.
  5. Cancer Genome Atlas Research Network, Linehan WM, Spellman PT, et al. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma. N Engl J Med 2016;374(2):135–45.
  6. Decision Resources Report: Renal Cell Carcinoma. October 2014 (internal data on file).
  7. American Society of Clinical Oncology. Cancer.Net. Treatment of Metastatic Castration-Resistant Prostate Cancer. September 8, 2014. Available at: https://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer. Accessed March 2021.
  8. Scher, H.I., Solo, K., Valant, J., Todd, M.B., Mehra, M. Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model. PLOS ONE. 2015; 10: e0139440.
  9. American Urological Association. Prostate Cancer: Castration Resistant Guideline. 2018. Available at: https://www.auanet.org/guidelines/prostate-cancer-castration-resistant-guideline. Accessed March 2021.
  10. Moreira, D. M., Howard, L. E., Sourbeer, K. N., et al. Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin Genitourin Cancer. 2017; 15: 60–66.e2.
  11. Hurwitz, M. et al. Urothelial and Kidney Cancers. Cancer Management. http://www.cancernetwork.com/cancer-management/urothelial-and-kidney-cancers. Accessed March 2021.
  12. American Cancer Society. Bladder Cancer Key Statistics. https://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics. Accessed March 2021.
  13. National Cancer Institute. SEER Stat Fact Sheets: Bladder Cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed March 2021.
  14. International Agency for Research on Cancer. GLOBOCAN 2020. Liver Fact Sheet. Available at: http://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf. Accessed March 2021.
  15. Rawla, P., Sunkara, T., Muralidharan, P., & Raj, J. P. 2018. Update in global trends and aetiology of hepatocellular carcinoma. Contemporary oncology (Poznan, Poland), 22(3), 141–150.
  16. Weledji E, Orock G, Ngowe M, NsaghaD. How grim is hepatocellular carcinoma? Ann Med Surg. 2014. 3:71-76.
  17. American Cancer Society. About Thyroid Cancer. Available at: https://www.cancer.org/cancer/thyroid-cancer/about.html. Accessed March 2021.
  18. Cooper DS, et al. 2009. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 19:1167–1214.
  19. Worden F. 2014. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol. 6:267–279.
  20. Xing M, Haugen BR, Schlumberger M. 2013. Progress in molecular-based management of differentiated thyroid cancer. Lancet. 381:1058–1069.
  21. Pacini F, et al. 2012. Radioactive iodine-refractory differentiated thyroid cancer: unmet needs and future directions. Expert Rev Endocrinol Metab. 7:541–554.
  22. Durante C, et al. 2006. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 91:2892–2899.
  23. Decision Resources Group. Thyroid Cancer. Diagnosed medullary incident cases – by geography. 2017.
  24. American Cancer Society. About Lung Cancer. https://www.cancer.org/content/dam/CRC/PDF/Public/8703.00.pdf. Accessed March 2021.
  25. American Society of Clinical Oncology. Cancer.Net. Lung Cancer – Non-Small Cell: Statistics.
    https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics. Accessed March 2021.
  26. National Cancer Institute. SEER Stat Fact Sheets: Lung and Bronchus Cancer. https://seer.cancer.gov/statfacts/html/lungb.html. Accessed March 2021.

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