Advancement in Treatment of Rare Cancers in the Era of Precision Oncology

Keerthi Ranganathan

Scientific Content Developer
4baseCare

Rare cancers are extremely difficult to treat. Treatment of rare cancers is difficult because they’re understudied, and patients with them frequently have limited access to clinical trials and few, if any, standard treatment options. They have a poor prognosis when diagnosed at an advanced stage, the main reasons being two-fold: delay in diagnosis and limited therapeutic options.

Precision oncology as a way of treatment of rare cancers has evolved to focus on matching the most accurate and effective therapies to the patient’s genetic profile and cancer, as well as other unique factors that differentiate one patient from another. By examining a simple blood/tumor sample for genes and proteins, researchers are now able to find appropriate targeted therapies for individuals with rare cancers. According to the findings of a recent study, doing genetic analysis on individuals with rare cancers might lead to novel therapies for them. 

Advances in precision cancer medicine can be used to define the genomic alterations in rare cancers DNA that is driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic and genomic testing, including DNA/RNA sequencing, to identify cancer-driving abnormalities in cancer’s genome. Once a genetic abnormality has been found, targeted treatment can be developed to target a specific aberration or other cancer-related genetic alteration/mutation in the cancer cells’ DNA programming. Precision oncology today involves using a combination of each patient’s unique molecular genetic profile to direct immunotherapy and targeted therapies specifically at cancer cells with particular aberrations while leaving normal cells mostly unaffected. 

The precision medicine era has brought in new findings that have led to novel treatments and potential treatments for rare cancers. Checkpoint inhibitors, which are immunotherapy drugs, were approved in 2017 to treat Merkel cell carcinoma, an exceedingly rare form of skin cancer, and Hodgkin lymphoma, a rare blood disease. Other rare cancers, such as thymic cancer and mesothelioma, are also being studied as possible candidates for immunotherapy.

Pembrolizumab was administered as a single agent in patients with advanced uncommon malignancies whose tumors had progressed on standard therapies, according to Naing et al (2020). The objective response rate was 14%, with the other 25% of patients experiencing illness stability for four months or more. Tawbi et al. (2017) evaluated pembrolizumab for safety and effectiveness in patients with advanced soft-tissue or bone sarcoma in a single-arm, phase II trial (SARC028). Pembrolizumab showed significant activity in patients with undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma, with response rates of 40% and 20%, respectively. The US Food and Drug Administration has authorized Cemiplimab, a PD-1 inhibitor, for the treatment of locally progressed or metastatic SCC of the skin. In metastatic patients, an objective response rate of 47% was recorded (Migden et al 2018).

The MOSCATO study (NCT01566019) employs high-throughput molecular analysis to guide targeted treatment for individuals with advanced malignancies. The trial looked at each of the 43 cases of advanced biliary tract cancer independently and found that molecular targeted drugs could be administered in 18 of them, with six of them showing an objective response (Verlingue et al 2018).

The genetic distinctions between intrahepatic, extrahepatic, and gallbladder cancers have been emphasized by mutation profiling (Jain et al 2016). NTRK gene fusions were discovered in intrahepatic cholangiocarcinomas using next-generation sequencing (NGS), and responses to larotrectinib have been documented (Cocco et al 2018). Her2/neu amplification is seen in 15% of gallbladder tumors, which might be targeted with antiHER2 treatments, while DNA repair mutations are found in 10-15% of cholangiocarcinomas, which could be treated with immune therapies (Colomer et al 2020).